No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
The effects of hypothermia on human left ventricular contractile function during cardiac surgery
Abstract
We investigated the interaction of heart rate (HR), temperature and contractility using a validated load independent method.
Temperature manipulation is an integral part of cardiac surgery, and postoperative hypothermia is extremely common. Myocardial contraction is a series of enzymatic and physico-chemical reactions that may be differentially affected by temperature.
Ten patients undergoing coronary artery bypass grafting were studied during moderately hypothermic cardiopulmonary bypass. After conduit procurement and heparinization but before grafting, the patient was placed on cardiopulmonary bypass and rewarmed to 37 degrees C, and the left ventricle (LV) was instrumented with a conductance catheter allowing continuous pressure and volume measurement. The LV pressure volume relationship was examined to assess the contractility at 37, 35, 33 and 31 degrees C, with fixed atrial pacing (100 beats/min) in five patients and at 80 and 120 beats/min, at 33 and 37 degrees C in five patients.
At a HR of 100 beats/min, lower temperature resulted in a highly significant decrease in maximal elastance (100% at 37 degrees C, 29 +/- 3.5% at 31 degrees C, p < 0.0001). At 37 degrees C, increasing HR increased contractility (80 beats/min 100%, 120 beats/min 205.9%, p = 0.0021); however, at 33 degrees C contractility fell with increasing HR (80 beats/min 100%, 120 beats/min, 53.7%, p = 0.0014).
At normothermia LV contractility has a direct relationship with HR. In hypothermic conditions this relationship inverses. Clinical strategies maintaining higher HRs at colder temperatures result in reduced contractility. These factors are important in the management of cardiac surgical patients.
... It has complex and opposite effects on myocardial muscle and on its contractility depending on the patient's volume status and the level of sedation that the patient is under [8,17,22]. Under normal conditions, moderate hypothermia decreases the heart rate and increases myocardial contractility in sedated and normovolaemic patients [5,[10][11][12][13]23,24]. Arterial pressure remains stable or may increase slightly in most moderate hypothermic patients [2,23,[25][26][27][28]. ...
... It has complex and opposite effects on myocardial muscle and on its contractility depending on the patient's volume status and the level of sedation that the patient is under [8,17,22]. Under normal conditions, moderate hypothermia decreases the heart rate and increases myocardial contractility in sedated and normovolaemic patients [5,[10][11][12][13]23,24]. Arterial pressure remains stable or may increase slightly in most moderate hypothermic patients [2,23,[25][26][27][28]. It has been shown; however, that severe hypothermia decreases myocardial contractility [4,25,29,30]. ...
... Krause et al. reported an additive aspect of the negative effects of shock and hypothermia on the haemodynamic and haemostasis parameters in a porcine study. The decrease in cardiac output and the coagulopathy persist, even after the bleeding has stopped and volume expanders have been used in the hypothermic animals [18,[23][24][25]38,39]. Wladis et al. have also confirmed the aggravation of the hypokinetic situation from haemorrhagic shock during hypothermia in an experimental study on pigs. ...
Hypothermia, along with acidosis and coagulopathy, is part of the lethal triad that worsen the prognosis of severe trauma patients. While accidental hypothermia is easy to identify by a simple measurement, it is no less pernicious if it is not detected or treated in the initial phase of patient care. It is a multifactorial process and is a factor of mortality in severe trauma cases. The consequences of hypothermia are many: it modifies myocardial contractions and may induce arrhythmias; it contributes to trauma-induced coagulopathy; from an immunological point of view, it diminishes inflammatory response and increases the chance of pneumonia in the patient; it inhibits the elimination of anaesthetic drugs and can complicate the calculation of dosing requirements; and it leads to an over-estimation of coagulation factor activities. This review will detail the pathophysiological consequences of hypothermia, as well as the most recent principle recommendations in dealing with it.
... There are several reports describing the effects of mild therapeutic hypothermia on the circulatory system [4,5] and only a few reports concerning severe hypothermia [6][7][8]. Hypothermia has been reported to affect left ventricular systolic and diastolic function [5,[7][8][9]. However, most of the data are derived from animal experimental studies [8][9][10][11]. ...
... There are several reports describing the effects of mild therapeutic hypothermia on the circulatory system [4,5] and only a few reports concerning severe hypothermia [6][7][8]. Hypothermia has been reported to affect left ventricular systolic and diastolic function [5,[7][8][9]. However, most of the data are derived from animal experimental studies [8][9][10][11]. ...
... Hypothermia has been reported to affect left ventricular systolic and diastolic function [5,[7][8][9]. However, most of the data are derived from animal experimental studies [8][9][10][11]. To the best of our knowledge, this is the first study to describe the effects of severe accidental hypothermia and invasive ECMO rewarming on ventricular function in survivors. ...
Accidental hypothermia is a condition associated with significant morbidity and mortality. Hypothermia has been reported to affect left ventricular systolic and diastolic function. However, most of the data come from animal experimental studies.
The purpose of the present study was to assess the impact of severe accidental hypothermia on systolic and diastolic ventricular function in patients treated using veno-arterial extracorporeal membrane oxygenation (ECMO).
We prospectively assessed nine hypothermic patients (8 male, age 25-78 years) who were transferred to the Severe Accidental Hypothermia Center and treated with ECMO. Transthoracic echocardiography was performed on admission (in patients without cardiac arrest) and on discharge from ICU after achieving cardiovascular stability. Cardiorespiratory stability and full neurologic recovery was achieved in all patients.
Biomarkers of myocardial damage (CK, CKMB, hsTnT) were significantly elevated in all study patients. Admission echocardiography performed in patients in sinus rhythm, revealed moderate-severe bi-ventricular systolic dysfunction and moderate bi-ventricular diastolic dysfunction. Discharge echocardiography showed persistent mild bi-ventricular diastolic dysfunction, although systolic function of both ventricles returned to normal. Discharge echocardiography in patients admitted with cardiac arrest showed normal (5 patients) or moderately impaired (1 patient) global LV systolic function on discharge. However, mild or moderate LV diastolic dysfunction was observed in all 6 patients. Discharge RV systolic function was normal, whereas mild RV diastolic dysfunction was present in these patients.
After severe accidental hypothermia bi-ventricular diastolic dysfunction persists despite systolic function recovery in survivors treated with ECMO.
... It has complex and opposite effects on myocardial muscle and on its contractility depending on the patient's volume status and the level of sedation that the patient is under [8,17,22]. Under normal conditions, moderate hypothermia decreases the heart rate and increases myocardial contractility in sedated and normovolaemic patients [5,[10][11][12][13]23,24]. Arterial pressure remains stable or may increase slightly in most moderate hypothermic patients [2,23,[25][26][27][28]. ...
... It has complex and opposite effects on myocardial muscle and on its contractility depending on the patient's volume status and the level of sedation that the patient is under [8,17,22]. Under normal conditions, moderate hypothermia decreases the heart rate and increases myocardial contractility in sedated and normovolaemic patients [5,[10][11][12][13]23,24]. Arterial pressure remains stable or may increase slightly in most moderate hypothermic patients [2,23,[25][26][27][28]. It has been shown; however, that severe hypothermia decreases myocardial contractility [4,25,29,30]. ...
... Krause et al. reported an additive aspect of the negative effects of shock and hypothermia on the haemodynamic and haemostasis parameters in a porcine study. The decrease in cardiac output and the coagulopathy persist, even after the bleeding has stopped and volume expanders have been used in the hypothermic animals [18,[23][24][25]38,39]. Wladis et al. have also confirmed the aggravation of the hypokinetic situation from haemorrhagic shock during hypothermia in an experimental study on pigs. ...
L’hypothermie fait partie, avec l’acidose et la coagulopathie, de la triade létale aggravant le pronostic des traumatisés graves. Si l’hypothermie accidentelle est facile à reconnaître par une simple mesure, elle n’en reste pas moins délétère si elle n’est pas prévenue ou traitée dès la phase initiale de la prise en charge du patient. Elle est multifactorielle et est un facteur de risque de mortalité chez le traumatisé grave. Les conséquences de l’hypothermie sont multiples : elle modifie la contractilité myocardique et favorise les arythmies. Elle participe à la coagulopathie traumatique. Du point de vue immunologique, elle diminue la réponse inflammatoire et augmente le taux de pneumopathies chez le traumatisé. Elle diminue l’élimination des médicaments utilisés pour l’anesthésie et la sédation et perturbe l’interprétation des dosages biologiques en particulier, elle entraîne une surestimation de l’activité des facteurs de la coagulation. Cette mise au point se propose de détailler les conséquences physiopathologiques de l’hypothermie, ainsi que les principales recommandations récemment formulées sur ce thème.
... Only cooling induced by TLV prevented transmural infarction and provided cardioprotection Ristagno (2010) 20 Isolated ventricular myocytes exposed to normal perfusion or ischaemia-reperfusion in rats, cooled from 37 • C to 34 • C, 32 • C, and 30 • C Increased contractility Gotberg (2010) 23 Ischaemic cardiogenic shock pig model cooled to 33 • C Cardiac output increased slightly, HR decreased, SV increased, acute mortality reduced Baumgart (2010) 36 Mice cooled from 38 • C to 27 • C LV ejection fracture increased from 44% to 50% Post (2010) 18 Pigs at 33 • C Decrease in diastolic function Filseth (2010) 17 Pigs cooled to 25 • C for 1 h Reduced systolic but not diastolic ventricular function, (increase in troponin T levels during rewarming) Clinical observations in adult patients Moriyama (1996) 47 Hypothermia (33 • C) combined with intra-aortic balloon pump support to low cardiac output state after open heart surgery Better outcome Kuwagata (1999) 48 Patients with severe head injury with mild hypothermia (33.5-34.5 • C) for 48 h Attenuated peak velocity of LV posterior wall movement during systole and diastole Lewis (2002) 34 Five patients undergoing coronary artery bypass grafting, cooled to 33 • C Improvement in systolic function with HR = 80 bpm but contractility decreased when HR = 120 bpm Hovdenes (2007) 49 Out-of-hospital cardiac arrest −32 to 34 • C Better outcome Bergman (2010) 35 Out-of-hospital cardiac arrest, 32.5 • C for 24 h Cardiac output and MAP decreased despite increased vasopressors and inotropes Jacobshagen (2010) 21 Cardiac arrest survivors: mild hypothermia (∼35.4 • C) Stabilised haemodynamics LV: left ventricular; SV: stroke volume; HR: heart rate; MAP: mean arterial pressure. ...
... Only cooling induced by TLV prevented transmural infarction and provided cardioprotection Ristagno (2010) 20 Isolated ventricular myocytes exposed to normal perfusion or ischaemia-reperfusion in rats, cooled from 37 • C to 34 • C, 32 • C, and 30 • C Increased contractility Gotberg (2010) 23 Ischaemic cardiogenic shock pig model cooled to 33 • C Cardiac output increased slightly, HR decreased, SV increased, acute mortality reduced Baumgart (2010) 36 Mice cooled from 38 • C to 27 • C LV ejection fracture increased from 44% to 50% Post (2010) 18 Pigs at 33 • C Decrease in diastolic function Filseth (2010) 17 Pigs cooled to 25 • C for 1 h Reduced systolic but not diastolic ventricular function, (increase in troponin T levels during rewarming) Clinical observations in adult patients Moriyama (1996) 47 Hypothermia (33 • C) combined with intra-aortic balloon pump support to low cardiac output state after open heart surgery Better outcome Kuwagata (1999) 48 Patients with severe head injury with mild hypothermia (33.5-34.5 • C) for 48 h Attenuated peak velocity of LV posterior wall movement during systole and diastole Lewis (2002) 34 Five patients undergoing coronary artery bypass grafting, cooled to 33 • C Improvement in systolic function with HR = 80 bpm but contractility decreased when HR = 120 bpm Hovdenes (2007) 49 Out-of-hospital cardiac arrest −32 to 34 • C Better outcome Bergman (2010) 35 Out-of-hospital cardiac arrest, 32.5 • C for 24 h Cardiac output and MAP decreased despite increased vasopressors and inotropes Jacobshagen (2010) 21 Cardiac arrest survivors: mild hypothermia (∼35.4 • C) Stabilised haemodynamics LV: left ventricular; SV: stroke volume; HR: heart rate; MAP: mean arterial pressure. ...
... 7 A clinical investigation also revealed that MTH decreased ventricular contractility when HR was paced at 120 beats/min. 34 However, in patients after cardiac arrest, Bergman et al. observed that MTH was associated with decreased HR and cardiac function, such that inotropic agents were needed to ensure adequate tissue perfusion. 35 The present study also investigated the consequences of changes in cardiac function on tissue perfusion, as evaluated by oxygen consumption, lactate levels and direct visualization of microvascular flow. ...
Introduction: Therapeutic hypothermia (TH) can improve neurological outcome after cardiac arrest (CA); little is known about how cooling actually affects brain dynamics after resuscitation from CA.
... Moreover, animal studies have shown that, in myocardial infarction, hypothermia decreases oxygen consumption and in farct size [8]. Th e positive inotropic eff ect of mild therapeutic hypothermia measured by systolic func tion has also been demonstrated in in vivo studies [5,9 ] an d can be measured echocardiographically by the signifi cant increase in ejection fraction (EF) and the augmented contraction velocity measured by pulse contour analysis. However, as shown by Lewis et al., increasing the heartrate (HR) under hypothermic conditions has a neg ative impact on LV contractility [9]. ...
... Th e positive inotropic eff ect of mild therapeutic hypothermia measured by systolic func tion has also been demonstrated in in vivo studies [5,9 ] an d can be measured echocardiographically by the signifi cant increase in ejection fraction (EF) and the augmented contraction velocity measured by pulse contour analysis. However, as shown by Lewis et al., increasing the heartrate (HR) under hypothermic conditions has a neg ative impact on LV contractility [9]. Although systolic performance is clearly improved at all temperature steps investigated, pronounced hypothermia may impair diastolic function [10]. ...
... This can also cause ischaemia of the RV resulting from increased wall tension and oxygen demand, as well as decreased coronary perfusion from an under-filled LV (10). In addition to affecting coagulation, hypothermia also exerts a negative effect on heart contractility (11). At higher HRs, the maximum contraction may not be reached, further decreasing CO (11). ...
... In addition to affecting coagulation, hypothermia also exerts a negative effect on heart contractility (11). At higher HRs, the maximum contraction may not be reached, further decreasing CO (11). ...
... Currently, there is a lack of consensus regarding the effects of hypothermia upon cardiac contractile function. Some studies have reported that hypothermia elicits a positive inotropic response (21,32), whereas others have reported no change (4,6,7,21) or a negative influence upon contractility (4,6,8,13). ...
... However, as observed here and by others, the FFR at 37°C is attenuated in the failing human heart (9,16). Although the FFR is reportedly impaired during hypothermia (13,15), we observed a significant increase in both F max and (dF/dt) max when stimulation frequency went from 0.5 to 1.0 Hz at 33°C that did not increase further at lower temperatures or higher frequency (Fig. 2, B and C). That higher stimulation frequency increased (dF/dt) max more than the F max (~40 and~15%, respectively; Fig. 2, B and C) may result from a modest increase in F max accompanied by a more substantial reduction in the length of the CRC (see Fig. 4 and Table 3). ...
Targeted temperature management (TTM) is part of the standardized treatment for cardiac arrest patients. Hypothermia decreases cerebral oxygen consumption and induces bradycardia, thus, increasing the heart rate may be considered to maintain cardiac output. We hypothesized that increasing heart rate during hypothermia would impair diastolic function. Human left ventricular trabeculae obtained from explanted hearts of patients with terminal heart failure were stimulated at 0.5 Hz and contraction-relaxation cycles recorded. Maximal developed force (Fmax), maximal rate of development of force ((dF/dt)max), time to peak force (TPF), time to 80% relaxation (TR80) and relaxation time (RT=TR80-TPF) were measured at 37-33-31-29°C. At these temperatures, stimulation frequency was increased from 0.5 to 1.0 to 1.5 Hz. At 1.5 Hz, concentration-response curves for the beta-adrenergic receptor (β-AR) agonist isoproterenol were performed. Fmax, TPF and RT increased when temperature was lowered, whereas the (dF/dt)max decreased. At all temperatures, increasing stimulation frequency increased Fmax and (dF/dt)max, whereas TPF and RT decreased. At 31 and 29°C, resting tension increased at 1.5 Hz, which was ameliorated by β-AR stimulation. At all temperatures, maximal β-AR stimulation increased Fmax, (dF/dt)max and maximal systolic force, whereas resting tension decreased progressively with lowering temperature. β-AR stimulation reduced TPF and RT to the same extent at all temperatures, despite the more elongated contraction-relaxation cycle at lower temperatures. Diastolic dysfunction during hypothermia results from an elongation of the contraction-relaxation cycle which decreases the time for ventricular filling. Hypothermic bradycardia protects the heart from diastolic dysfunction and increasing the heart rate during hypothermia should be avoided.
... [5] The increase in heart rate artifi cially through administration of chronotropic drugs or pacing wire, leads to decrease in myocardial contractility. [9] Cardiac output ...
... The increase in heart rate artifi cially through the administration of chronotropic drugs or pacing wire, leads to decrease in myocardial contractility. [9] Atropine is ineffective in this condition. The risk of arrhythmia is low as long as the core temperature is above 30°C. ...
Targeted temperature management (TTM) in today's modern era, especially in intensive care units represents a promising multifaceted therapy for a variety of conditions. Though hypothermia is being used since Hippocratic era, the renewed interest of late has been since early 21 st century. There have been multiple advancements in this field and varieties of cooling devices are available at present. TTM requires careful titration of its depth, duration and rewarming as it is associated with side-effects. The purpose of this review is to find out the best evidence-based clinical practice criteria of therapeutic hypothermia in critical care settings. TTM is an unique therapeutic modality for salvaging neurological tissue viability in critically ill patients viz. Post-cardiac arrest, traumatic brain injury (TBI), meningitis, acute liver failure and stroke. TTM is standard of care in post-cardiac arrest situations; there has been a lot of controversy of late regarding temperature ranges to be used for the same. In patients with TBI, it reduces intracranial pressure, but has not shown any favorable neurologic outcome. Hypothermia is generally accepted treatment for hypoxic ischemic encephalopathy in newborns. The current available technology to induce and maintain hypothermia allows for precise temperature control. Future studies should focus on optimizing hypothermic treatment to full benefit of our patients and its application in other clinical scenarios.
... However, a concomitant increase in duration of the cardiac action potential and time to maximal contraction, with increased left ventricular stiffness and prolonged relaxation time [20], may result in a reduced overall ability of the heart to perform work during mild hypothermia. This is particularly noticeable when HR is artificially increased during TH, which results in a decrease in contractility [21]. Indeed, it appears that the hypothermia-induced increase in myocardial contractility can only occur if HR is allowed to fall [21]. ...
... This is particularly noticeable when HR is artificially increased during TH, which results in a decrease in contractility [21]. Indeed, it appears that the hypothermia-induced increase in myocardial contractility can only occur if HR is allowed to fall [21]. Thus, studies suggest that left ventricular contractility and SV during mild hypothermia may be increased, unaffected or reduced, and this is likely to be due to a combination of the degree of hypothermia, anaesthetic regimen, and use of additional inotropic agents during TH. ...
... Secondary outcomes were intensive care unit (ICU) and 30-day mortality, severity of circulatory shock assessed by mean arterial pressure, serum lactate, fluid balance and the extended Sequential Organ Failure assessment (SOFA) score. Results: There was no significance difference between targeted temperature management at 33°C or 36°C on 180-day mortality [log-rank test, p = 0.17, hazard ratio 1. 33 ...
... could be determined for best cardiovascular performance in each individual patient [14]. Diastolic dysfunction is commonly reported as a negative consequence of a target temperature of 33°C [30,33,34]. The reduced heart rate, commonly observed during hypothermia, is thought to oppose the negative effect of reduced left ventricular relaxation but we did not observe a significant reduction in heart rate at 33°C in this study, which might be due to a lack of power [14,15,17,18,30,34]. ...
Purpose
We hypothesized that a targeted temperature of 33 °C as compared to that of 36 °C would increase survival and reduce the severity of circulatory shock in patients with shock on admission after out-of-hospital cardiac arrest (OHCA).
Methods
The recently published Target Temperature Management trial (TTM-trial) randomized 939 OHCA patients with no difference in outcome between groups and no difference in mortality at the end of the trial in a predefined subgroup of patients with shock at admission. Shock was defined as a systolic blood pressure of 30 min or the need of supportive measures to maintain a blood pressure ≥90 mmHg and/or clinical signs of end-organ hypoperfusion. In this post hoc analysis reported here, we further analyzed the 139 patients with shock at admission; all had been randomized to receive intervention at 33 °C (TTM33; n = 71) or 36 °C (TTM36; n = 68). Primary outcome was 180-day mortality. Secondary outcomes were intensive care unit (ICU) and 30-day mortality, severity of circulatory shock assessed by mean arterial pressure, serum lactate, fluid balance and the extended Sequential Organ Failure assessment (SOFA) score.
Results
There was no significance difference between targeted temperature management at 33 °C or 36 °C on 180-day mortality [log-rank test, p = 0.17, hazard ratio 1.33, 95 % confidence interval (CI) 0.88–1.98] or ICU mortality (61 vs. 44 %, p = 0.06; relative risk 1.37, 95 % CI 0.99–1.91). Serum lactate and the extended cardiovascular SOFA score were higher in the TTM33 group (p
... Las razones teóricas para su empleo son: disminuir la actividad metabólica y las demandas de oxígeno, evitar lesiones neurológicas en caso de fallo en el aporte de oxígeno, posibilitar la disminución del flujo de perfusión sanguínea y un menor retorno venoso a través de vasos bronquiales y colaterales no coronarios. (23,25,26) Se describen los siguientes grados según la temperatura rectal: 32 a 35,9º C, ligera; 28 a 32º C, moderada; 18 a 28º C, severa, y menor de 18º C, profunda. (19) La hipotermia no solo induce efectos adversos sobre el miocardio, a saber: edema celular, alteración de la estabilidad de las membranas celulares, de la entrega de oxígeno, su consumo y la generación de energía; sino que dificulta también las funciones metabólicas del glucógeno, así como las endocrinas, particularmente tiroideas, lo que provoca disminución de la contractilidad miocárdica y retardo en el inicio de la función mecánica cardiaca. ...
... (19) La hipotermia no solo induce efectos adversos sobre el miocardio, a saber: edema celular, alteración de la estabilidad de las membranas celulares, de la entrega de oxígeno, su consumo y la generación de energía; sino que dificulta también las funciones metabólicas del glucógeno, así como las endocrinas, particularmente tiroideas, lo que provoca disminución de la contractilidad miocárdica y retardo en el inicio de la función mecánica cardiaca. (6,7,14,(24)(25)(26) Al reducir las demandas metabólicas ayuda a proteger las células neuronales, pero empeora la regulación vasomotora y el aporte de oxígeno cerebral, altera el metabolismo energético e incrementa la presión intracraneal lo que induce daño celular tras la reperfusión. (27) No menos importante es tener presente que en pacientes pediátricos la hipotermia y hemodilución pueden descender el hematocrito por debajo de un punto crítico comprometiendo el aporte de oxígeno al cerebro. ...
La hipotermia durante la circulación extracorpórea es un método comúnmente utilizado en cirugía cardiovascular infantil, pero existen evidencias de que induce efectos nocivos. La normotermia como alternativa novedosa en cirugía pediátrica fue introducida por Lecompte en 1995 y actualmente nueve centros europeos acumulan una experiencia de 12 000 intervenciones durante los últimos 15 años. Los reportes clínicos muestran menor incidencia de complicaciones, disminución en el uso de inotrópicos, menores tiempos de circulación extracorpórea, de ventilación mecánica y de estadía en terapia intensiva al compararla con la hipotermia. Se realizó una revisión bibliográfica con el objetivo de identificar elementos fisiopatológicos durante la circulación extracorpórea en normotermia e hipotermia en la cirugía cardiovascular pediátrica, como marco teórico para introducir la normotermia como modalidad de primera elección. Se concluye que la normotermia es una técnica más fisiológica, capaz de proteger los diferentes órganos y sistemas de forma segura y eficaz.
... Myocardial stiffening associated with lower myocardial temperature might be responsible for increase in end-systolic and end-diastolic elastance. Meanwhile, increasing the heart rate by pacing has been shown to impair systolic function and also to worsen diastolic dysfunction (40). These results suggest mechanistic importance of prolonged systole for maintaining systolic function. ...
Therapeutic hypothermia has been used for treating brain injury after out-of-hospital cardiac arrest. Its potential benefit on minimizing myocardial ischemic injury has been explored, but clinical evidence has yet to confirm positive results in preclinical studies. Importantly, therapeutic hypothermia for myocardial infarction is unique in that it can be initiated prior to reperfusion, in contrast to its application for brain injury in resuscitated cardiac arrest patients. Recent advance in cooling technology allows more rapid cooling of the heart than ever and new clinical trials are designed to examine the efficacy of rapid therapeutic hypothermia for myocardial infarction. In this review, we summarize current knowledge regarding the effect of hypothermia on normal and ischemic hearts and discuss issues to be solved in order to realize its clinical application for treating acute myocardial infarction.
... The strengths of this study are the standardized definition of hypothermia ( ≤ 36.6°C) and the use of digital axillary temperature. In contrast, previous studies have used various cutoff points to define hypothermia [10,17], which allow for precise evaluation of the association with mortality [9]. However, changes in the definition of hypothermia can eliminate noticeable changes in mortality (e.g., using 36°C and comparing 35.9°C vs. 36.1°C, ...
Background:
Postoperative body temperature is closely associated with prognosis although there is limited research regarding this association at Postoperative intensive care unit (ICU) admission. Furthermore, no studies have used digital axillary thermometers to measure Postoperative body temperature. This study investigated the association between mortality and Postoperative temperature measured using a digital axillary thermometer within 10 minutes after ICU admission.
Methods:
This retrospective observational study evaluated data from adult patients admitted to an ICU after elective or emergency surgery. The primary outcome was 1-year mortality after ICU admission. Multivariable logistic regression analysis with restricted cubic splines was used to evaluate the association between temperature and outcomes.
Results:
We evaluated data from 5,868 patients admitted between January 1, 2013 and May 31, 2016, including 5,311 patients (90.5%) who underwent noncardiovascular surgery and 557 patients (9.5%) who underwent cardiovascular surgery. Deviation from the median temperature (36.6℃) was associated with increases in 1-year mortality (≤ 36.6℃: linear coefficient, -0.531; P<0.001 and ≥36.6℃: spline coefficient, 0.756; P<0.001). Similar statistically significant results were observed in the noncardiovascular surgery group, but not in the cardiovascular surgery group.
Conclusions:
An increase or decrease in body temperature (vs. 36.6℃) measured using digital axillary thermometers within 10 minutes of Postoperative ICU admission was associated with increased 1-year mortality. However, no significant association was observed after cardiovascular surgery. These results suggest that Postoperative temperature is associated with longterm mortality in patients admitted to the surgical ICU in the Postoperative period.
... The strengths of this study are the standardized definition of hypothermia (≤36.6ºC) and the use of digital axillary temperature. In contrast, previous studies have used various cutoff points to define hypothermia [10,17], which allow for precise evaluation of the association with mortality [9]. However, changes in the definition of hypothermia can eliminate noticeable changes in mortality (e.g., using 36ºC and comparing 35.9°C vs. 36.1°C, ...
... Studies have shown that CO in cooled neonates is approximately 2/3 of their normothermic baseline (78). Although myocardial contractility may be enhanced during TH due to an increased sensitivity to calcium, it may be counterbalanced by an increase in left ventricular wall stiffness, time to maximal contraction, and relaxation time (79,80). Within the context of these myocardial changes, the increased contractility may be most effective at the slower heart rate and chronotropic effect of vasoactive medications may not be beneficial but detrimental. ...
Asphyxiated neonates often have hypotension, shock, and poor tissue perfusion. Various “inotropic” medications are used to provide cardiovascular support to improve the blood pressure and to treat shock. However, there is incomplete literature on the examination of hemodynamic effects of these medications in asphyxiated neonates, especially in the realm of clinical studies (mostly in late preterm or term populations). Although the extrapolation of findings from animal studies and other clinical populations such as children and adults require caution, it seems appropriate that findings from carefully conducted pre-clinical studies are important in answering some of the fundamental knowledge gaps. Based on a literature search, this review discusses the current available information, from both clinical studies and animal models of neonatal asphyxia, on common medications used to provide hemodynamic support including dopamine, dobutamine, epinephrine, milrinone, norepinephrine, vasopressin, levosimendan, and hydrocortisone.
... Apart from surgery, neuraxial anesthesia used for cesarean delivery has also been demonstrated to impair normal autonomic thermoregulatory control, exacerbate inadvertent perioperative hypothermia and thereby may increase the risk of blood loss, hypotension and fluid requirement 7,8 . Finally, studies have shown that patients with warmer body temperatures tend to experience less acidosis, better cardiac contractility and lower incidence of hypotension 2,4 . We assumed that preventing hypothermia not only decreases the incidence of hypotension but also reduces the fluid and transfusion requirements. ...
Background/Aim: This study was undertaken to test whether warming IV fluids (37oC) results in lower incidence of hypotension, less ephedrine and transfusion requirement and lower fluid consumption than use of room-temperature fluids (22°C) in cesarean delivery patients undergoing spinal anesthesia. Materials and Methods: We studied 63 parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia. Parturients were allocated randomly as un-warmed fluid group (Group C, n=30) and warmed fluid group (Group W, n=30). Maternal body temperatures, the incidence of hypotension, ephedrine and transfusion requirements, total fluid volumes, and side effects were recorded. Results: Maternal body temperatures were significantly higher in the warmed group compared with the un-warmed group only at 15 min (p=0.02). There was no significant difference between the two groups in the incidence of hypotension (70% (21/30), 56.7% (17/30) in Group C and W respectively). Fluid requirement and ephedrine consumptions were similar between the two groups and no patient needed blood transfusion. Conclusion: In cesarean section patients undergoing spinal anesthesia, warming IV fluids (37°C) resulted in lower incidence of decreased core temperature but did not affect the incidence of maternal hypotension, ephedrine and transfusion requirement and volume consumption.
... In these invasive investigations, real-time pressure was measured using a micromanometer and volume was assessed using the conductance method. Conventional determination of the end-systolic P-V relationship from multiple P-V loops was performed at varying preload, and E es was calculated as the slope of this end-systolic P-V relationship (1,3,6,10,11,18,19,21,23,24,26,28,(31)(32)(33)(34). ...
End-systolic left ventricular (LV) elastance (Ees) has been previously calculated and validated inva-sively using LV pressure-volume (P-V) loops. Noninvasive methods have been proposed, but clinical application remains complex. The aims of the present study were to 1) estimate Ees according to modeling of the LV P-V curve during ejection (“ejection P-V curve” method) and validate our method with existing published LV P-V loop data and 2) test the clinical applicability of noninvasively detecting a difference in Ees between normotensive and hypertensive subjects. On the basis of the ejection P-V curve and a linear relationship between elastance and time during ejection, we used a nonlinear least-squares method to fit the pressure waveform. We then computed the slope and intercept of time-varying elastance as well as the volume intercept (V0). As a validation, 22 P-V loops obtained from previous invasive studies were digitized and analyzed using the ejection P-V curve method. To test clinical applicability, ejection P-V curves were obtained from 33 hypertensive subjects and 32 normotensive subjects with carotid tonometry and real-time three-dimensional echocardiography during the same procedure. A good univariate relationship (r² = 0.92, P ☓ 0.005) and good limits of agreement were found between the invasive calculation of Ees and our new proposed ejection P-V curve method. In hypertensive patients, an increase in arterial elastance (Ea) was compensated by a parallel increase in Ees without change in Ea/Ees. In addition, the clinical reproducibility of our method was similar to that of another noninvasive method. In conclusion, Ees and V0 can be estimated noninvasively from modeling of the P-V curve during ejection. This approach was found to be reproducible and sensitive enough to detect an expected increase in LV contractility in hypertensive patients. Because of its noninvasive nature, this methodology may have clinical implications in various disease states. NEW & NOTEWORTHY The use of real-time three-dimensional echocardiography-derived left ventricular volumes in conjunction with carotid tonometry was found to be reproducible and sensitive enough to detect expected differences in left ventricular elastance in arterial hypertension. Because of its noninvasive nature, this methodology may have clinical implications in various disease states.
... In the intact pig however, cooling induce a reduction of cardiac contractile function and SV [33]. Lewis and colleagues showed that the inotropic effect of increasing heart rate during normothermic conditions in man, is lost at a core temperature of 33°C [71], independent of pharmacologic interventions. Consequently, hypothermia-induced changes in physiology, not related to ligand-receptor kinetics, could also be involved in altered pharmacodynamics of β-adrenoceptor agonists during hypothermic conditions. ...
Rewarming from accidental hypothermia is often complicated by hypothermia-induced cardiac dysfunction, calling for immediate pharmacologic intervention. Studies show that although cardiac pharmacologic support is applied when rewarming these patients, a lack of updated treatment recommendations exist. Mainly due to lack of clinical and experimental data, neither of the international guidelines includes information about pharmacologic cardiac support at temperatures below 30 °C. However, core temperature of accidental hypothermia patients is often reduced below 30 °C. Few human studies exploring effects of adrenergic drugs during hypothermia have been published, and therefore prevailing information is collected from pre-clinical studies. The most prominent finding in these studies is an apparent depressive effect of adrenaline on cardiac function when used in doses which elevate cardiac output during normothermia. Also noradrenaline and isoprenaline largely lacked positive cardiac effects during hypothermia, while dopamine is a more promising drug for supporting cardiac function during rewarming. Data and information from these studies are in support of the prevailing notion; not to use adrenergic drugs at core temperatures below 30 °C.
... It can decrease the oxygen consumption of the tissue, delay the adenosine triphosphate (ATP) consumption when tissue is ischemia [11] . The mild hypothermia can improve the organization of ischemia hypoxia tolerance [12] , side effect as its influence on blood coagulation function and so on. But in our study, we did not observe any complication of clinical relevance associated with mild hypothermia, especially bleeding, thrombosis, arterial or pulmonary embolism and no adverse haemodynamic events. ...
ABSTRACT Objective: To summarize the effect of mild hypothermia on function of the organs in patients with multiple organ dysfunction syndrome after cardiopulmonary bypass surgery. Methods: The patients were randomly divided into two groups, northermia group (n=71) and hypothermia group (n=89). We immediately began cooling the hypothermia group when test results showed multiple organ dysfunction syndrome, meanwhile all patients of two groups were drawn blood to test blood gas, liver and kidney function, blood coagulation function, and evaluated the cardiac function using echocardiography from 12 to 36 hours. We compared the difference of intra-aortic balloon pump, extracorporeal membrane oxygenation rate and mortality within one month after intensive care unit admission. Results: Among the 160 patients, 36 died, 10 (11.24%) patients were from the hypothermia group and 26 (36.6%) from the northermia group (P
... The cardioprotective effect is not limited to its recognized reduction of infarct size, but also results in conservation of post-ischaemic contractile function, prevention of no-reflow or microvascular obstruction, and ultimately attenuation of left ventricular remodeling [43]. However, hypothermia depresses myocardial contraction and slows conduction [25], leading to serious cardiac output, rate, and rhythm disturbances which may be manifested as hypertension, bradycardia, premature ventricular contractions, or ventricular fibrillation. The metabolism of cardioprotective effect is dramatically reduced [39], and acidosis and cellular calcium and sodium overload are dramatically attenuated because contractile activity is arrested along with most enzymatic activity [2]. ...
Hypothermia has positive and negative consequences on the body. Hypothermia depresses myocardial contraction, conduction, and metabolic rate in the heart. However, little is known about the underlying molecular mechanisms. Herein, we compared the gene expression of human adult ventricular cardiomyocytes (AC16) under hypothermia to find differences between different temperatures, and elucidate the candidate genes that may play important roles in the response to hypothermia. A total of 2413 differentially expressed genes (DEGs) were identified by microarray hybridization, which provided abundant data for further analysis. Gene Ontology (GO) enrichment analysis revealed that genes related to transcription, and protein and lipid metabolism were significantly enriched. KEGG analysis showed that DEGs were significantly enriched in TGF-β pathway and cytokine-cytokine receptor interaction, which may play important roles in changes affected by hypothermia. A set of transcription factors (TFs) (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333, ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key nodes, which mapped the signal of hypothermia to transcriptome. The identified DEGs, pathways and predicted TFs could facilitate further investigations of the detailed molecular mechanisms.
... 4 However, hemodynamic instability is common in comatose OHCA survivors, because of post-cardiac arrest syndrome, and may be exacerbated by induction of TTM. 5 Previous studies have suggested that systemic vascular resistance increases with TTM, while cardiac output decreases in parallel with the heart rate. 6 However, other studies in patients with vasopressor-dependency after cardiac arrest showed that induction of TTM was not associated with a decrease in mean arterial pressure or increase in vasopressor requirement, and TTM was not associated with total cumulative vasopressor index (CVI), survival, or a good outcome. 7,8 However, these studies investigated the relationship between TTM and vasopressor requirements in the management of OHCA with cardiogenic shock, in which vasopressors are needed to increase myocardial contractility. ...
Objective
We investigated whether patients with out-of-hospital cardiac arrest (OHCA) due to an acute myocardial infarction without cardiogenic shock required higher doses of vasopressors with low targeted temperature management (TTM) after return of spontaneous circulation.
Methods
We included consecutive comatose patients resuscitated from OHCA between January 2011 and December 2013. Patients with return of spontaneous circulation, regional wall motion abnormality on echocardiography, and coronary artery stenosis of ≥70% on percutaneous coronary artery angiography were enrolled. These patients received 36°C TTM or 33°C TTM following approval of TTM by patients’ next-of-kin (36°C and 33°C TTM groups, respectively). The cumulative vasopressor index was compared between groups.
Results
During induction phase, dose of vasopressors did not differ between groups. In the maintenance phase, the norepinephrine dose was 0.37±0.57 and 0.26±0.91 µg·kg⁻¹·min⁻¹ in the 33°C and 36°C TTM groups, respectively (P<0.01). During the rewarming phase, the norepinephrine and dopamine doses were 0.49±0.60 and 9.67±9.60 mcg·kg⁻¹·min⁻¹ in the 33°C TTM group and 0.14±0.46 and 3.13±7.19 mcg·kg⁻¹·min⁻¹ in the 36°C TTM group, respectively (P<0.01). The median cumulative vasopressor index was 8 (interquartile range, 3 to 8) and 4 (interquartile range, 0 to 8) in the 33°C and 36°C TTM groups, respectively (P=0.03).
Conclusion
In this study, patients with OHCA due to acute myocardial infarction without cardiogenic shock had an elevated vasopressor requirement with 33°C TTM compared to 36°C TTM during the maintenance and rewarming phases.
... Hypothermia results in a not only decreased metabolic rate but also lower cardiac output, mainly due to decreased HR from slowed depolarization in the sinus node. As HR decreases, myocardial contractility increases, and conversely, when HR is increased with positive chronotropic agents or a pacemaker, contractility decreases (16,17). The authors postulate that patients with severe hypoxic-ischemic brain injuries may have a blunted parasympathetic response to hypothermia when compared with those with milder insults (6). ...
... The results showed an impaired contractility when the HR was artificially sustained during hypothermia, demonstrating that an elevated HR during hypothermia has a negative effect on contractility in humans. 69 In parallel, the decrease in body temperature is accompanied by an upsurge of catecholamine release into the blood stream. This increases the stroke volume (SV), leading to an initial improvement in cardiac output (CO). ...
Targeted temperature management has been originally used to reduce neurological injury and improve outcome in patients after out-of-hospital cardiac arrest. Myocardial infarction remains a major cause of death in the world and several investigators are studying the effect of mild therapeutic hypothermia during an acute cardiac ischemic injury. A search on MEDLINE, Scopus and EMBASE databases was conducted to obtain data regarding the cardioprotective properties of therapeutic hypothermia. Preclinical studies have shown that therapeutic hypothermia provides a cardioprotective effect in animals. The proposed pathways for the cardioprotective effects of therapeutic hypothermia include stabilization of mitochondrial permeability, production of nitric oxide, equilibration of reactive oxygen species, and calcium channels homeostasis. Clinical trials in humans have yielded controversial results. Current trials are therefore seeking to combine therapeutic hypothermia with other treatment modalities in order to improve the outcomes of patients with acute ischemic injury. This article provides a review of the hypothermia effects on the cardiovascular system, from the basic science of physiological changes in the human body and molecular mechanisms of cardioprotection to the bench of clinical trials with therapeutic hypothermia in patients with acute ischemic injury.
... Besides, some studies suggest that the relation between heart rate and cardiac output inverses with hypothermia and that allowing mild TH to reduce heart rate could actually improve myocardial contractility. This is explained because hypothermia worsens diastolic function in the myocardium, and this is partially balanced by bradycardia [24,25] . External pacing or administration of chronotropic drugs is not recommended during TH to increase cardiac output [16] . ...
To assess the safety of therapeutic hypothermia (TH) concerning arrhythmias we analyzed serial electrocardiograms (ECG) during TH.
All patients recovered from a cardiac arrest with Glasgow < 9 at admission were treated with induced mild TH to 32-34 °C. TH was obtained with cool fluid infusion or a specific intravascular device. Twelve-lead ECG before, during, and after TH, as well as ECG telemetry data was recorded in all patients. From a total of 54 patients admitted with cardiac arrest during the study period, 47 patients had the 3 ECG and telemetry data available. ECG analysis was blinded and performed with manual caliper by two independent cardiologists from blinded copies of original ECG, recorded at 25 mm/s and 10 mm/mV. Coronary care unit staff analyzed ECG telemetry for rhythm disturbances. Variables measured in ECG were rhythm, RR, PR, QT and corrected QT (QTc by Bazett formula, measured in lead v2) intervals, QRS duration, presence of Osborn's J wave and U wave, as well as ST segment displacement and T wave amplitude in leads II, v2 and v5.
Heart rate went down an average of 19 bpm during hypothermia and increased again 16 bpm with rewarming (P < 0.0005, both). There was a non-significant prolongation of the PR interval during TH and a significant decrease with rewarming (P = 0.041). QRS duration significantly prolonged (P = 0.041) with TH and shortened back (P < 0.005) with rewarming. QTc interval presented a mean prolongation of 58 ms (P < 0.005) during TH and a significant shortening with rewarming of 22.2 ms (P = 0.017). Osborn or J wave was found in 21.3% of the patients. New arrhythmias occurred in 38.3% of the patients. Most frequent arrhythmia was non-sustained ventricular tachycardia (19.1%), followed by severe bradycardia or paced rhythm (10.6%), accelerated nodal rhythm (8.5%) and atrial fibrillation (6.4%). No life threatening arrhythmias (sustained ventricular tachycardia, polymorphic ventricular tachycardia or ventricular fibrillation) occurred during TH.
A 38.3% of patients had cardiac arrhythmias during TH but without life-threatening arrhythmias. A concern may rise when inducing TH to patients with long QT syndrome.
... Hypothermia is an integral part of cardiac surgery, and postoperative patients frequently are mildly hypothermic despite rewarming on cardiopulmonary bypass (CPB). Clinical [11] and experimental [12] studies in relation to CPB have demonstrated reduced cardiac performance during mild hypothermia which was particularly pronounced at increased heart rates. However, there are also opposite findings demonstrating improved left ventricular function after CPB in experimental animals [13]. ...
Systolic left ventricular function during therapeutic hypothermia is found both to improve and to decline. We hypothesized that this discrepancy would depend on the heart rate and the variables used to assess systolic function.
In 16 pigs, cardiac performance was assessed by measurements of invasive pressures and thermodilution cardiac output and with 2D strain echocardiography. Left ventricle (LV) volumes, ejection fraction (EF), transmitral flow, and circumferential and longitudinal systolic strain were measured. Miniaturized ultrasonic transducers were attached to the epicardium of the LV to obtain M-mode images, systolic thickening, and diastolic thinning velocities and to determine LV pressure-wall dimension relationships. Preload recruitable stroke work (PRSW) was calculated. Measurements were performed at 38 and 33°C at spontaneous and paced heart rates, successively increased in steps of 20 up to the toleration limit. Effects of temperature and heart rate were compared in a mixed model analysis.
Hypothermia reduced heart rate from 87 ± 10 (SD) to 76 ± 11 beats/min without any changes in LV stroke volume, end-diastolic volume, EF, strain values, or PRSW. Systolic wall thickening velocity (S') and early diastolic wall thinning velocity decreased by approximately 30%, making systolic duration longer through a prolonged and slow contraction and changing the diastolic filling pattern from predominantly early towards late. Pacing reduced diastolic duration much more during hypo- than during normothermia, and combined with slow myocardial relaxation, incomplete relaxation occurred with all pacing rates. Pacing did not affect S' or PRSW at physiological heart rates, but stroke volume, end-diastolic volume, and strain were reduced as a consequence of reduced diastolic filling and much more accentuated during hypothermia. At the ultimate tolerable heart rate during hypothermia, S' decreased, probably as a consequence of myocardial hypoperfusion due to sustained ventricular contraction throughout a very short diastole.
Systolic function was maintained at physiological heart rates during therapeutic hypothermia. Reduced tolerance to increases in heart rate was caused by lack of ventricular filling due to diastolic dysfunction and shorter diastolic duration.
... [8] Hypothermia-induced reduction in cardiac output and heart rate are interdependent [8] and often offset by a reduction in metabolic rates, which in turn reduces the body's metabolic demand. [60] Cold diuresis resulting from peripheral vasoconstriction and elevated venous return, however, may constitute a challenge when maintaining blood volume and should be effectively managed to avoid a precipitous drop in blood pressure and increase in vascular viscosity. [8] These are generally associated with the early stages of hypothermia induction (i.e. the induction phase), but are not normally serious complications, except when they are accompanied by shivering. ...
Prognosis following out-of-hospital cardiac arrest is generally poor, which is mostly due to the severity of neuronal damage. Recently, the use of therapeutic hypothermia has gradually occupied an important role in managing neuronal injuries in some cases of cardiac arrests. Some of the clinical trials conducted in comatose post-resuscitation cardiac arrest patients within the last decade have shown induced hypothermia to be effective in facilitating neuronal function recovery. This method has since been adopted in a number of guidelines and protocols as the standard method of treatment in carefully selected patient groups. Patient inclusion criteria ensure that hypothermia-associated complications are kept to a minimum while at the same time maximizing the treatment benefits. In the present work, we have examined different aspects in the use of therapeutic hypothermia as a means of managing comatose patients following cardiac arrest.
... However, the effect of temperature on myocardial contractility is not fully elucidated, and previous results reported that myocardial contractility may vary according to heart rate. 19 Our results suggested that reduced myocardial contractility played a minor role in decreasing cardiac output as neither LVEF nor s′ as markers of myocardial contractility differed between TTM groups, and importantly adjustment for heart rate did not change these results. Improvement in systolic function with improved myocardial contractility with diastolic function being negatively affected during hypothermia has been reported in an animal model using conductance catheter. ...
Background
Either deep hypothermia with circulatory arrest or hypothermic perfusion with antegrade selective cerebral perfusion is used during the Norwood procedure for hypoplastic left heart syndrome. Normothermic perfusion has been described for pediatric patients. The aim of this study was to compare the early outcomes of patients undergoing the Norwood procedure with antegrade selective cerebral perfusion under hypothermia with the procedure under normothermia.
Methods
From 2005 to 2020, 117 consecutive patients with hypoplastic left heart syndrome underwent the Norwood procedure: 68 (58.2%) under hypothermia and 49 (41.8%) under normothermia. Antegrade selective cerebral perfusion flow was adjusted to maintain right radial arterial pressure above 50 mm Hg, and a flow rate of 40 to 50 mL kg ⁻¹ min ⁻¹ . Baseline characteristics, operative data, and postoperative outcomes including lactate recovery time were compared.
Results
The baseline characteristics and cardiovascular diagnosis were similar in both groups. The normothermic group had a significantly shorter bypass time (in minutes) of 90.31 (±31.60) versus 123.63 (±25.33), a cross-clamp time of 45.24 (±16.35) versus 81.93 (±16.34), and an antegrade selective cerebral perfusion time of 25.61 (±13.84) versus 47.30 (±14.35) ( P < .001). There were no statistically significant differences in the immediate postoperative course, or in terms of in-hospital mortality, which totaled 9 (18.4%) in the normothermic group, and 10 (14.9%) in the hypothermic group ( P = .81).
Conclusion
The normothermic Norwood procedure with selective cerebral perfusion is feasible and safe in terms of in-hospital mortality and short-term outcomes. It is comparable to the standard hypothermic Norwood with selective cerebral perfusion.
Background:
Liver transplant centers vary in approach to intraoperative vascular accesses, monitoring of cardiac function and temperature management. Evidence is limited regarding impact of selected modalities on postoperative outcomes.
Objectives:
To review the literature and provide expert panel recommendations on optimal intraoperative arterial BP, CVP and vascular accesses, monitoring of cardiac function and intraoperative temperature management regarding immediate and short-term outcomes after OLT.
Methods:
Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Recommendations made for: 1. Vascular accesses, arterial BP and CVP monitoring 2. Cardiac function monitoring and 3. Intraoperative temperature management (CRD42021239908).
Results:
Of 2619 articles screened 16 were included. Studies were small, retrospective, and observational. Vascular access studies demonstrated low rates of insertion complications. TEE studies demonstrated low rates of esophageal hemorrhage. One study found lower hospital-LOS and 30-day mortality in patients monitored with both PAC and TEE. Other monitoring studies were heterogenous in design and outcomes. Temperature studies showed increased blood transfusion and ventilation times in hypothermic groups.
Conclusions:
Recommendations were made for; routine arterial and CVP monitoring as a minimum standard of practice, consideration of discrepancy between peripheral and central arterial BP in patients with hemodynamic instability and high vasopressor requirements, and routine use of high flow cannulae whilst monitoring for extravasation and hematoma formation. Availability and expertise in PAC and/or TEE monitoring is strongly recommended particularly in hemodynamic instability, portopulmonary HT and/or cardiac dysfunction. TEE use is recommended as an acceptable risk in patients with treated esophageal varices and is an effective diagnostic tool for emergency cardiovascular collapse. Maintenance of intraoperative normothermia is strongly recommended. This article is protected by copyright. All rights reserved.
Objectives:
Targeted temperature management (32-36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts.
Design:
Prospective clinical study, from June 2015 to May 2018.
Setting:
Cardiothoracic surgery operation room, Oslo University Hospital.
Patients:
Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included.
Interventions:
Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36°C, 32°C prior to graft-replacement, and at 36°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions.
Measurements and main results:
Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ± 170 to 1,156 ± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ± 0.07 and 0.57 ± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ± 0.05 and 0.47 ± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored.
Conclusions:
In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming.
Therapeutic hypothermia has been used for millennia, but more recently, targeted temperature management has caught physician’s interest as the main neuroprotective strategy for cardiac arrest patients who remain comatose after return of spontaneous circulation. Randomized clinical trials have shown benefits in neurologic and mortality outcomes when lowering body’s core temperature to mild-to-moderate ranges of hypothermia, in conjunction with strict hyperthermia prevention measurements. The International Liaison Committee on Resuscitation recommends in their current guidelines to use a target temperature between 32 °C and 36 °C, for at least 24 h, in post-cardiac arrest patients, regardless of their initial rhythm (shockable vs. non-shockable). Therapeutic hypothermia consists of three well-defined phases: induction, maintenance, and rewarming. Each of these phases has very specific physiologic and clinical considerations for optimal patient management. The optimal dose, the induction and maintenance method, and the temperature monitoring technique remain unclear and are the focus of future research. Despite the overwhelmingly positive data regarding the benefits of therapeutic hypothermia, this technique remains underused. Clinicians should be familiar with this therapeutic intervention.
Introduction:
Targeted temperature management (TTM) is a well-accepted neuro-protective intervention in the management of comatose survivors of cardiac arrest (CA). However, the impact of TTM on cardiac performance has not been adequately evaluated.
Methods:
We reviewed data on consecutive CA survivors undergoing TTM at a quaternary cardiac intensive care unit between January 2015 and June 2017. Enrollment was restricted to cases with invasive hemodynamics (iHDs) at TTM initiation, every 8 h at target temperature (32-34 °C) and at completion of rewarming (>36 °C), unless precluded by mortality. Cardiac index and cardiac index-derived variables were adjusted for a decreased oxygen consumption during hypothermia. We assessed the serial impact of cooling on iHDs and cardiac performance utilizing longitudinal data analysis accounting for the effects of time as surrogate for the expected change from the post arrest syndrome and instituted treatments. A Frank-Starling construct was used to evaluate changes in cardiac contractility.
Results:
We evaluated the effects of cooling on iHDs and cardiac performance in 46 CA survivors. Heart rate decreased with cooling (p < 0.001), to return to baseline after rewarming (p = 0.6). Mean arterial pressure and pulmonary wedge pressure decreased by cooling (p < 0.001 for both), with sustained improvement after rewarming (p < 0.001 for both). Systemic vascular resistance was unaffected by hypothermia (p > 0.05). Left stroke work index increased with cooling (p < 0.001), with return to baseline after rewarming (p = 0.6). Cooling was associated with a left-upward shift in the Frank-Starling curve indicative of increased contractility.
Conclusion:
Mild hypothermia in CA survivors appears associated to positive changes in iHDs and cardiac performance, including a potential increase in cardiac contractility. Larger studies are needed to conclusively confirm these findings.
A 3-year-10-month-old female neutered Dachshund was presented for investigation of acute onset paraparesis. Magnetic resonance imaging showed an intervertebral disc extrusion, therefore a dorsal hemilaminectomy was performed. While under general anaesthesia, the patient became hypothermic (33.1 °C) and severely bradycardic, with a concurrent severe decrease in blood pressure. Initial management of the bradycardia included glycopyrrolate at a dose rate of 10 μg/kg, administered twice, however the patient was unresponsive to this. Active warming was initiated and the patient's body temperature slowly increased. A single dose of atropine was administered, following which the patient's bradycardia resolved. It is likely that once the patient's temperature increased, all the vasoactive substances were able to take effect. This suggests that the bradycardia was probably, in part, due to the hypothermia, although other factors may have contributed.
Deep hypothermia for the operative correction of congenital cardiac lesions protects hypoperfused organs, mostly because of its effect on lowering metabolic demand and oxygen requirement. Deleterious cerebral and extracranial side effects of deep hypothermia itself calls for a reexamination of the therapeutic value of hypothermia, and has led to the development of alternative perfusion strategies. Here we describe the potential advantages of milder hypothermia over deep hypothermia and our method of a practical and reproducible implementation of multisite perfusion under mild hypothermia (32°C).
Hypothermia can inadvertently occur in patients undergoing non-cardiac surgery leading to an increase in surgical site infections, coagulopathy, and shivering with an increased oxygen demand. The definition of hypothermia is presented, as well as the physiologic impact on various organs. During cardiopulmonary bypass in cardiac surgery it is also used for neuroprotection, with special attention paid to temperature monitoring site, rewarming, and the avoidance of hyperthermia. The neuroprotective effects of therapeutic hypothermia after cardiac arrest are also discussed in this chapter.
Background Accumulating evidence indicates that target temperature management (TTM) is benefi cial in patients resuscitated after cardiac arrest since it appears to improve neurological outcome. However, the optimal cooling method (surface vs intravascular) has not yet been specifi ed. Substantial heart disease is present in most of these patients and therefore haemodynamic eff ects of cooling need to be considered very carefully. We analysed the haemodynamic response to TTM in patients treated with surface versus intravascular cooling following out-of-hospital cardiac arrest.
Methods and results In this observational study 63 consecutive subjects presenting to the hospital after successful resuscitation following of out-of-hospital cardiac arrest received an intravascular (40 patients) or external cooling device (23 patients) to induce TTM. While with intravascular cooling the target temperature of 33°C was reached after 159 minutes, the minimum temperature achieved with surface cooling was about 35°C after 437 minutes. Haemodynamic parameters were recorded in a 4-hour rhythm for the fi rst 12 hours after induction of hypothermia. Generally, TTM of 33°C resulted in a higher systemic vascular resistance index (749 vs 467 dyn*sec/cm5/m²; P= 0.04) but also in a marked reduction of heart rate (67.70 vs 100.00 bpm; P < 0.001), a higher mixed venous oxygen saturation (76 vs 68%; P= 0.016), and a higher stroke volume index (45 vs 33 ml/m²; P= 0.036). TTM additionally resulted in a higher cardiac power index (0.55 vs 0.46 Watt/m²; P= 0.024).
Conclusion TTM of 33°C compared to 35°C exerts benefi cial haemodynamic eff ects and might be viewed as an adjunct inotropic therapy avoiding the undesired side eff ects of vasoactive substances.
Aim:
To evaluate post-cardiac arrest myocardial dysfunction during prolonged targeted temperature management (TTM) compared with standard TTM in comatose out-of-hospital cardiac arrest (OHCA) survivors.
Methods:
A randomised, controlled trial comparing myocardial function after TTM at 33 ±1°C for 48h compared with 24h. A total of 105 OHCA patients were computer-randomised to 24h (n=50) or 48h (n=55) of TTM. Transthoracic echocardiography was performed after 24h, 48h and 72h. Echocardiographic parameters were evaluated by an investigator who was blinded to randomisation. The primary endpoint was peak systolic mitral annular velocity (Ś) measured as the difference in the period from 24h to 72h. The model was adjusted for age, primary rhythm and heart rate. The secondary outcomes were global peak longitudinal strain, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE) and the diastolic measures e' and E/e'.
Results:
The mean difference of S' was significantly increased in the 48h group compared with the 24h group: -1.14cm/sec (-1.83; -0.45), p=0.001. This difference was consistent after adjusting the data (p=0.008). However, there were no significant changes between the study groups with respect to the adjusted secondary outcomes of global peak longitudinal strain (p=0.07), LVEF (p=0.31), TAPSE (p=0.91), e' (p=0.26) and E/e' (p=0.18).
Conclusion:
Prolonged TTM at 33°C of 48h compared with 24h in comatose OHCA survivors may improve the recovery of post-cardiac arrest left myocardial dysfunction demonstrated by the echocardiographic outcome, S'. ClinicalTrials.gov identifier: NCT02066753.
Objective:
To review current knowledge surrounding the effects, treatment, and prognosis of hypothermia in people, dogs, and cats, as well as the application of therapeutic hypothermia in clinical medicine.
Etiology:
Hypothermia may be a primary or secondary condition, and may be due to environmental exposure, illness, medications, anesthesia, or trauma. Hypothermia has been applied therapeutically in human medicine for a variety of conditions, including postcardiac arrest. In veterinary medicine, the technique has been applied in cardiac surgeries requiring bypass and in a patient with intractable seizures.
Diagnosis:
Hypothermia can be diagnosed based on presenting temperature or clinical signs, and appropriate diagnosis may require nontraditional thermometers.
Therapy:
Rewarming is the primary treatment for accidental hypothermia, with intensity ranging from passive surface rewarming to extracorporeal rewarming. The goal is to return the core temperature to a level that restores normal physiologic function of all body processes. Other supportive therapies such as intravenous fluids are typically indicated, and if cardiopulmonary arrest is present, prolonged resuscitation may be required. In cases of secondary hypothermia, reversal of the underlying cause is important.
Prognosis:
There are few prognostic indicators in human and veterinary patients with hypothermia. Even the most severely affected individuals, including those presenting in cardiopulmonary arrest, have potential for complete recovery with appropriate therapy. Therapeutic hypothermia has been shown to improve outcome in people following cardiac arrest. Further studies are needed to examine this application in veterinary medicine, as well as appropriate therapy and prognosis for cases of spontaneous hypothermia.
Background: The ascertainment of brain death (the irreversible, total loss of brain function) gives the physician the opportunity to limit or stop further treatment. Alternatively, if the brain-dead individual is an organ donor, the mode of treatment can be changed from patient-centered to donation-centered. Consensus-derived recommendations for the organ-protective treatment of brain-dead organ donors are not yet available in Germany.
Methods: This review is based on pertinent publications retrieved by a
selective search in PubMed, and on the authors clinical experience.
Results: Brain death causes major pathophysiological changes, including an increase in catecholamine levels and a sudden drop in the concentration of multiple hormones, among them antidiuretic hormone, cortisol, insulin, and tri- and tetraiodothyronine. These changes affect the function of all organ systems, as well as the hemodynamic state and the regulation of body temperature. The use of standardized donor management protocols might well increase the rate of transplanted organs per donor and improve the quality of the transplanted organs. In addition, the administration of methylprednisolone, desmopressin, and vasopressin could be a useful supplement to treatment in some cases. Randomized controlled trials have not yet demonstrated either improved organ function or prolonged survival of the transplant recipients.
Conclusion: The evidence base for organ-protective intensive care is weak; most of the available evidence is on the level of expert opinion. There is good reason to believe, however, that the continuation of intensive care, in the sense of early donor management, can make organ transplantation more successful both by increasing the number of transplantable organs and by improving organ quality.
Atherosclerotic heart disease is the leading cause of death in developed nations. Manifestations include myocardial ischemia or infarction. In addition, some patients develop cardiovascular insufficiency, with the additional risk of systemic ischemia. Hypothermia has been shown to protect tissues during ischemia and thus may have clinical benefit in patients with cardiovascular disorders. This chapter will explore the potential therapeutic role for hypothermia in regional and global myocardial ischemia, as well as systemic ischemia secondary to heart failure.
Background:
Accumulating evidence indicates that target temperature management (TTM) is beneficial in patients resuscitated after cardiac arrest since it appears to improve neurological outcome. However, the optimal cooling method (surface vs. intravascular) has not yet been specified. Substantial heart disease is present in most of these patients and therefore haemodynamic effects of cooling need to be considered very carefully. We analysed the haemodynamic response to TTM in patients treated with surface versus intravascular cooling following out-of-hospital cardiac arrest.
Methods and results:
In this observational study 63 consecutive subjects presenting to the hospital after successful resuscitation following of out-of-hospital cardiac arrest received an intravascular (40 patients) or external cooling device (23 patients) to induce TTM. While with intravascular cooling the target temperature of 33 degrees C was reached after 159 minutes, the minimum temperature achieved with surface cooling was about 35 degrees C after 437 minutes. Haemodynamic parameters were recorded in a 4-hour rhythm for the first 12 hours after induction of hypothermia. Generally, TTM of 33 degrees C resulted in a higher systemic vascular resistance index (749 vs. 467 dyn*sec/cms/m2; P= 0.04) but also in a marked reduction of heart rate (67.70 vs. 100.00 bpm; P < 0.001), a higher mixed venous oxygen saturation (76 vs. 68%; P = 0.016), and a higher stroke volume index (45 vs. 33 mI/m2; P = 0.036). TTM additionally resulted in a higher cardiac power index (0.55 vs. 0.46 Watt/m2; P = 0.024).
Conclusion:
TTM of 33 degrees C compared to 35 degrees C exerts beneficial haemodynamic effects and might be viewed as an adjunct inotropic therapy avoiding the undesired side effects of vasoactive substances.
Zur Betrachtung der Hämodynamik unter milder therapeutischer Hypothermie bei cardiogenem Schock wurden 40 Patienten, die zuvor mindestens fünf Minuten cardio-pulmonal reanimiert werden mussten, in die Studie eingeschlossen. Nach der Akutversorgung erfolgte die Kühlung auf 33°C Körpertemperatur. Die Studie umfasste 12 Frauen (30%) und 28 Männer (70%) mit einem Durchschnittsalter von 65 Jahren. 26 Patienten (66%) verstarben innerhalb von 90 Tagen. Dabei überlebten 12 der 21 Patienten unter 70 Jahren (57%), hingegen nur zwei der 19 älteren Erkrankten (11%). Von den 14 Überlebenden entwickelten 13 ein gutes und nur ein Patient ein schlechtes neurologisches Outcome. Die Messung der Gefäßdurchmesser und Blutflussgeschwindigkeiten mittels Duplexsonographie erfolgte in HT und NT in den Aa. subclaviae, Aa. carotides internae und Aa. vertebrales jeweils beidseits sowie in A. brachialis, A. radialis, A. femoralis und A. dorsalis pedis nur auf einer Körperseite. Daraus wurden die Gefäßinnenfläche A sowie die maximale Volumenstromstärke I in Systole und Enddiastole berechnet. In HT zeigte sich ein kleineres Lumen in A. brachialis, A. radialis, A. subclavia rechts und A. vertebralis links. Die maximale systolische Blutflussgeschwindigkeit Vms war in A. dorsalis pedis und A. carotis interna rechts in HT niedriger. Auch herrschte eine signifikant geringere maximale enddiastolische Blutflussgeschwindigkeit während HT in der A. dorsalis pedis sowie in beiden Aa. carotides internae. Die Volumenstromstärke I zeigte im Vergleich mit der Blutflussgeschwindigkeit V in deutlich mehr Gefäßen einen signifikant niedrigeren Wert in HT. In der Systole waren dies die A. brachialis, A. radialis, A. dorsalis pedis und A. vertebralis links sowie beide Aa. subclaviae und beide inneren Carotiden. Zum Zeitpunkt der Enddiastole war I signifikant niedriger in A. brachialis, A. dorsalis pedis sowie in beiden inneren Carotiden. Eine Beeinflussung von Ims und Imed durch das Patientenalter oder hypotone Zustände in HT bzw. NT zeigte sich nicht.
Aufgrund der beobachteten Gefäßinnenflächen wäre anzunehmen, dass die HT vor allem in den peripheren Arterien eine Gefäßkonstriktion mit erhöhtem Gefäßwiderstand bedingt. Auch die verringerten systolischen und diastolischen Geschwindigkeiten in der A. dorsalis pedis könnten auf Zentralisierungsvorgänge während HT zurückzuführen sein. Es zeigte sich aber aufgrund der gemessenen Blutflussgeschwindigkeiten in beiden inneren Carotiden, dass bei 33°C auch eine verlangsamte Blutflussgeschwindigkeit zum Gehirn erfolgt. Daher ist anhand der Volumenstromstärken in den vier hirnversorgenden und den peripheren Arterien festzu-stellen, dass in HT ein insgesamt geringerer Fluss herrschte als in NT. Somit scheint in HT keine Zentralisierung zugunsten des Gehirns stattzufinden. Jedoch kann anhand der Studie mangels Bestimmung des systemischen vaskulären Widerstands und des Herzzeitvolumens nicht abschließend geklärt werden, in wieweit die globale Perfusionsabnahme cardialer, vaskulärer oder hypovolämischer Ursache ist.
L’hypothermie définie par une température inférieure ou égale à 35°C est fréquemment rencontrée en réanimation. Elle peut être soit accidentelle, soit thérapeutique et semble alors jouer un rôle de protection dans certains processus d’ischémie-reperfusion. L’hypothermie a de multiples conséquences cardiaques et vasculaires, incluant une bradycardie succédant à une tachycardie première, une conservation initiale de la contractilité myocardique en cas d’hypothermie légère à modérée, avec une stabilité ou une baisse de l’index cardiaque s’accentuant dans les hypothermies plus profondes. Il existe également une diminution des besoins métaboliques myocardiques et globaux, avec augmentation de la SvO2 rendant la balance délivrance/consommation en oxygène stable ou favorable, malgré l’hypoxie et l’hypocapnie usuelles. L’hypothermie induit enfin une augmentation des résistances vasculaires périphériques, malgré une diminution de la réponse aux catécholamines, et une tendance à l’hypovolémie essentiellement liée à la diurèse induite par le froid.
La plupart de ces éléments, associés à une possible cardioprotection spécifique, paraissent favorables à l’hypothermie. Cependant, l’hypothermie est également associée à des risques, notamment rythmiques (fibrillation atriale initialement, puis ventriculaire en dessous de 30–32℃), métaboliques (hydro-électrolytique, pharmacocinétique), ainsi qu’à des perturbations de la coagulation pouvant parfois induire des conséquences cardiovasculaires délétères. La profondeur précise du contrôle thermique — incluant l’hypothermie légère — est actuellement débattue dans l’arrêt cardiaque et l’anoxie néonatale. L’hypothermie thérapeutique reste une voie de recherche prometteuse dans le traitement de l’état de choc cardiogénique et la revascularisation de l’infarctus du myocarde.
It has been suggested that the increased incidence of ventricular arrhythmias recognized below 30°C might be catecholamine mediated. Elevated catecholamine concentrations have been reported in experimentally induced hypothermia in animals. Plasma concentrations of epinephrine and norepinephrine were measured during profound hypothermia and total circulatory arrest in infants under one year of age undergoing surgical correction of congenital cardiac defects. There was no significant change in either epinephrine or norepinephrine levels during surface cooling to 28° C. Circulatory arrest and exsanguination at 18° C were not associated with a rise in catecholamine levels. However, there was a striking rise in the levels of both epinephrine and norepinephrine with the recommencement of bypass and rewarming. The mean plasma norepinephrine concentration rose from 466 pg/ml (SE ± 81) at circulatory arrest to 4543 pg/ml (SE ± 2058) on rewarming bypass (p
The mechanical responses (active and resting tension, dP/dt, TPT) and ionic exchange characteristics (Ca(++), K(+), Na(+)) which follow upon a variation in temperature, rate, and [K(+)](o) were studied in the rabbit papillary muscle and arterially perfused rabbit interventricular setpum. Abrupt changes in temperature provided a means of separating the contributions of rate of development (intensity) of active state and duration of active state to total active tension development (approximated by isometric tension). Threefold changes in duration of active state with proportional changes in active tension can be induced without evidence for alteration of Ca(++), K(+), or Na(+) exchange. Abrupt cooling produced a moderate ( approximately 15%) increase of dP/dt which suggests an augmentation of active state intensity. Evidence is presented to suggest that this increase of dP/dt is based upon an increase in membrane Ca(++) concentration which occurs secondary to inhibition of active Na(+) transport. The alterations in ionic exchange and active state produced by variation of temperature are discussed in terms of a five-component control system.
~,1247R. T. Tregear and ~. B. Marston 1Agricultural Research Council Unit of Muscle Mechanism and InsectPhysiology, Department of Zoology, University of Oxford, Oxford, EnglandINTRODUCTIONThis review treats the central issues in present-day research on the problemof contraction itself. In the first section we give a brief account of the severalschools of experimental study that have dominated the field over the lasthalf century and show how they have given rise to the crossbddge theory.In the second we describe more fully the logic of the present form of thetheory and the way in which different experimental modes interact toproduce this logic. The final section contains a brief commentary on theprobable developments in the near future. Because our article is fitted tovery strict limits on length, we have omitted much detail from the evidence.Many detailed reviews of particular aspects of the contractile process haveappeared in the last few years and may be used to add ttesh to our bare bones(17, 35, 40, 52, 72, 74, 77, 79, 82).PAST"Muscle, which is the instrument of voluntary movement ... becomesthicker, shortens and gathers itself together and so draws to itself and movesthe part to which it is attached" [Vesalius, 1543 (63)]. How it does so hasbecome a lot dearer in the last forty years, and is now almost a propersubject of molecular biology; the terms we use are approaching a descriptionof events during contraction at atomic resolution and millisecond timescale, but they are not there yet.The steady-state mechanics of active muscle were described in the firsthalf of the century in terms of the twin relations between force and either~Present address~ICI Pharmaceuticals, Mereside, Alderley Park, Macclestield, Cheshire,England7230066-4278/79/0301-0723 $01.00www.annualreviews.org/aronline Annual Reviews
We investigated the effects of hypothermia (25 degrees C) on the chronotropic and inotropic effects of zatebradine (a blocker of hyperpolarization-activated inward current, I(f)), E-4031 (a blocker of the rapid type of the delayed rectifier K+ current, I(Kr)) and verapamil, and on the positive cardiac responses to isoproterenol after treatment with zatebradine and E-4031 in isolated, blood-perfused dog atria. Hypothermia shifted the dose-response curves to the right for the negative chronotropic and inotropic effects of verapamil and for the negative chronotropic and positive inotropic effects of zatebradine, but not for the negative chronotropic and positive inotropic effects of E-4031. Hypothermia attenuated the positive chronotropic response to isoproterenol or Bay k 8644 (an L type Ca2+ channel agonist) and was attenuated more than the inotropic one. Zatebradine selectively inhibited the positive chronotropic response to isoproterenol at a normal temperature, but in hypothermia, it inhibited neither the chronotropic nor inotropic responses. E-4031 did not affect the positive responses to isoproterenol. These results suggest that verapamil and zatebradine but not E-4031 influence the atrial rate and contractile force much less in hypothermia than in normothermia and that the I(f) and inward Ca2+ current are sensitive to hypothermia in the heart.
We investigated the effects of myocardial temperature on left ventricular (LV) mechanoenergetics in the excised, cross-circulated canine heart. We used the framework of the LV contractility (E(max))-pressure-volume area (PVA; a measure of total mechanical energy)-myocardial oxygen consumption (VO(2)) relationship. We have shown this framework to be useful to integrative analysis of the mechanoenergetics of a beating heart. In isovolumic contractions at a constant pacing rate, increasing myocardial temperature from 30 to 40 degrees C depressed E(max) and increased the oxygen cost of E(max), which was enhanced by dobutamine, in a linear manner. However, the slope of the VO(2)-PVA relation (reciprocal of contractile efficiency) and its VO(2) intercept remained constant. Q(10) values of E(max), the oxygen cost of E(max), and the oxygen cost of PVA were 0.4, 2.1 and 1.0, respectively, around normothermia. We conclude that the temperature-dependent processes of cross-bridge cycling and Ca(2+) handling integratively depress E(max) and augment its oxygen cost without affecting the oxygen cost of PVA as myocardial temperature increases by 10 degrees C around normothermia.
The mechanical responses (active and resting tension, dP/dt, TPT) and ionic exchange characteristics (Ca⁺⁺, K⁺, Na⁺) which follow upon a variation in temperature, rate, and [K⁺]o were studied in the rabbit papillary muscle and arterially perfused rabbit interventricular setpum. Abrupt changes in temperature provided a means of separating the contributions of rate of development (intensity) of active state and duration of active state to total active tension development (approximated by isometric tension). Threefold changes in duration of active state with proportional changes in active tension can be induced without evidence for alteration of Ca⁺⁺, K⁺, or Na⁺ exchange. Abrupt cooling produced a moderate (∼15%) increase of dP/dt which suggests an augmentation of active state intensity. Evidence is presented to suggest that this increase of dP/dt is based upon an increase in membrane Ca⁺⁺ concentration which occurs secondary to inhibition of active Na⁺ transport. The alterations in ionic exchange and active state produced by variation of temperature are discussed in terms of a five-component control system.
Lowering myocardial temperature increases contractile force, presumably by increasing intracellular calcium content. To study the mechanisms behind this, we compared the effects of some known inotropic interventions with hypothermia on mechanical restitution and post-rest contractile force in isolated guinea-pig papillary muscles. In four groups (n = 6 per group), the effects of: (1) reducing the ability for Na/Ca exchange to extrude Ca2+ (a) by increasing [Na+]i with ouabain or (b) by increasing [Ca2+]o; and (2) activation of calcium channels with Bay-K 8644, were compared with lowering temperature from 37 to 27-degrees-C. Normally (at 37-degrees-C and 2 mm CaCl2), mechanical restitution could be described by a rapid recovery phase with a time constant between 180 and 220 ms, followed by a slowly decaying phase with a time constant between 5000 and 8000 ms and post-rest contractions (1-10 min rest) were markedly depressed compared to steady-state contractions. Steady-state developed force was markedly increased at 27-degrees-C, after 1 muM ouabain, 6 mm CaCl2 or 0.1 muM Bay-K 8644. At 27-degrees-C the rapid recovery phase of restitution was delayed while the slowly decaying phase was not affected. Ouabain and increased [Ca2+]o caused elevation of the slowly decaying phase of restitution and markedly attenuated the post-rest depression of developed force, which may be attributed to a reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger. Hypothermia and Bay-K 8644 on the other hand, augmented this post-rest depression. Hence, this study suggests that increased Ca2+ influx due to delayed inactivation of calcium channels may account for the increased developed force during hypothermia rather than reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger.
We assessed the linearity and slope of the left ventricular end-systolic pressure (PES)-volume (VES) relation over a wide range of contractile states in conscious dogs. The animals were instrumented to determine left ventricular volume from ultrasonic left ventricular internal dimensions and measure left ventricular pressure with a micromanometer. Studies were performed 1-2 weeks after instrumentation while the animals were conscious. Contractile state was increased by incremental infusion of dobutamine (0, 2, 4, 6, and 8 micrograms/kg/min i.v.) and decreased by verapamil (10 mg i.v.) given after autonomic blockade. The 44 +/- 11 mm Hg (mean +/- SD) portion of the PES-VES relation generated by bicaval occlusion demonstrated a slight but consistent nonlinearity, apparent as a concavity toward the volume axis. This nonlinearity, present at all inotropic states, did not prevent the PES-VES relation from being well approximated by a straight line (r = 0.984 +/- 0.020, SEE = 2.1 +/- 1.4 mm Hg); furthermore, the slope of the PES-VES line provided a sensitive index of contractile state, progressively increasing with incremental doses of dobutamine and decreasing in response to verapamil. The volume-axis intercept of the linear approximation of the PES-VES relation was 2.9 +/- 3.3 ml less (p less than 0.05) than the volume-axis intercept of the nonlinear quadratic fit. Thus, the linear PES-VES relation, whose slope is sensitive to a wide variety of inotropic states, is a reasonable and useful description of the left ventricle in the range of PES-VES points that can be produced by bicaval occlusion in the conscious dog. However, linear extrapolation of the relation beyond the range of data points may not be accurate.
Although cardiopulmonary bypass support has been increasingly used for high risk coronary angioplasty, few data exist regarding its effects on left ventricular function. Accordingly, in 20 patients changes in left ventricular size, afterload and myocardial function were assessed by continuous hemodynamic monitoring and simultaneous two-dimensional echocardiography during cardiopulmonary bypass-supported high risk angioplasty.The cross-sectional left ventricular area during bypass support remained unchanged during diastole, whereas during systole it decreased (from 29.6 ± 11.4 to 27.6 ± 10.4 cm2, p < 0.05). Global left ventricular function expressed as fractional area change remained unchanged from baseline to bypass support but decreased during balloon inflation (from 0.27 ± 0.11 to 0.17 ± 0.09, p < 0.001). The end-systolic meridional wall stress decreased during bypass support (from 141 ± 75 to 110 ± 58 × 103 dynes/cm2, p < 0.02). Regional myocardial function was assessed by a wall motion score (0 = normal, 1 = hypokinesia, 2 = akinesia and 3 = dyskinesia). Regions supplied by a stenotic (≥ 50% diameter) vessel deteriorated during bypass support (score from 0.9 ± 0.8 to 1.06 ± 0.8, p < 0.01), whereas regions supplied by a nonslenotic vessel did not. Regions supplied by the target vessel deteriorated further during balloon inflation (score from 0.7 ± 0.6 to 1.7 ± 0.75, p < 0.001).Thus, although left ventricular size and global function remain unchanged and afterload decreases during bypass support, myocardial dysfunction in regions supplied by a stenotic vessel may occur. Furthermore, regional and global left ventricular dysfunction still occur with angioplasty balloon inflation during cardiopulmonary bypass support.
In six patients undergoing coronary vein graft operations under cardiopulmonary bypass and hypothermia, the temperatures of
arterial and mixed-venous blood, nasopharynx, oesophagus, liver, rectum, deltoid and vastus lateralis muscles and 10 skin
sites were recorded. Whole-body oxygen consumption was measured before cooling and twice during hypothermia. On average, a
patient lost 1000 kJ of heat by the end of hypothermia, of which 84% was lost to the heat-exchanger and pump circuit. Evaporative
and convective loss amounted to 380 kJ, while the patient's metabolism supplied 220 kJ. During rewarming, the pump returned
670 kJ to the patient. Nasopharyngeal temperature reflected accurately venous, oesophageal and hepatic temperatures in the
steady state; however, it was slow to reflect changes. Compared with other sites, muscle remains warmer during hypothermia
and cooler after rewarming.
Post-operative low cardiac output states remain a major cause of mortality following cardiac surgery in infants and children. Since 1979 we have used moderate induced whole-body hypothermia in the management of low-output states refractory to conventional modes of therapy. This is based not only upon the relationship between body temperature and oxygen consumption, but also on experimental work showing a beneficial effect of cooling upon myocardial contractility, particularly when there is pre-existing impairment of ventricular function. Between July 1986 and June 1990, 20 children with refractory low-output states were cooled by means of a thermostatically controlled water blanket to a rectal temperature of 32-33 degrees C. The median age was 12 months (1 week-11 years) with a median weight of 6 kg (3.5-33 kg). Ten children survived to leave hospital while a further two made a haemodynamic recovery. There was a marked reduction in heart rate (P < 0.001). The mean arterial pressure rose (P = 0.037) while there was a fall in mean atrial pressure (P < 0.001). There was a significant improvement in the urine output (P = 0.002). A fall in the platelet count (P < 0.001) was not accompanied by any change in the white cell count (P = 0.15). Although it is impossible to say whether cooling influenced the outcome in any of these children, it was usually effective in stabilising their clinical condition. The technique is simple and has a sound theoretical basis.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate the controversial effects of hypothermia on cardiac contractile performance, we have carried out ventricular volume-loading experiments in 23 perfused, paced (2 Hz), isolated rat hearts, contracting isovolumically at various temperatures. A water-filled, unstressed latex balloon was inserted into the left ventricle and its volume was controlled with a microsyringe. Left ventricular pressure (LVP), its first derivative (dP/dt) and coronary flow were recorded. One group of hearts (n = 7) were perfused at 37 degrees C over 2 h. Another group of hearts (n = 16) were cooled in a stepwise manner from 37 degrees C to 21 degrees C, with 10-min perfusion at each of seven different temperatures, and then rewarmed to 37 degrees C. Emax, an index of contractility, calculated as the slope of the regression line of the end-systolic pressure-volume relationship, was found to increase as temperature fell (3.9, 4.6, 4.9, 5.5, 5.5, 6.2, and 6.3 cm H2O/microliters at 37 degrees, 34 degrees, 31 degrees, 29 degrees, 27 degrees, 24 degrees and 21 degrees C, respectively) while it remained constant over the 2-h perfusion in the normothermic perfusion group. By contrast, peak positive dP/dt/peak-developed pressure (+dP/dt/DP) progressively decreased during cooling without any change in the normothermic perfusion group. The results indicate that hypothermia can be designated as a positive inotropic intervention in terms of force-generation (Emax) but as a negative inotropic intervention in terms of shortening velocity of contractile element in Hill's model (+dP/dt/DP).
A significant release of lactate instead of uptake was observed during the first 10 min of cardiopulmonary bypass preceding aorto-coronary bypass surgery in human patients. To clarify these findings in more detail, myocardial lactate and oxygen metabolism was studied in healthy dog hearts subjected to a protocol similar to the clinical situation. In one group (n = 11) normothermia at 34°C was used with an empty beating heart, and in the other group (n = 11) hypothermia with ventricular fibrillation was applied.
Within the first 10 min of bypass no significant changes in high energy phosphates were observed in myocardial biopsies. However, a marked decrease in mean aortic blood pressure and a simultaneous lowering in oxygen consumption was observed in both groups after instalment of bypass. An initial shift from lactate uptake to lactate release occurred while on bypass in the normothermia group. After 10 min of bypass, lactate uptake was restored in hearts of both groups. Therefore, the lactate release during the initial phase of bypass in patients originates both from the instalment of the bypass and from (local) inadequate perfusion, which is most likely to be due to stenosed coronary arteries.
Knowledge of the effects of cardiopulmonary bypass on the myocardium and on cardiac function is limited. We therefore studied changes in haemodynamics and myocardial metabolism during the initial phase of cardiopulmonary bypass in two patient groups. In one group "normothermia" (34 degrees C) was used while on bypass, with an empty beating heart; in the other group hypothermia (range 27-33 degrees C) with ventricular fibrillation was used. Mean aortic pressure and myocardial oxygen consumption decreased significantly in both groups after instalment of CPB. The arterial-coronary sinus differences in lactate changed to negative values within 5 min of the start of bypass, indicating release instead of uptake of lactate. This release was maintained during the observation period and increased significantly in the hypothermic patient group when the ventricles were fibrillating. Therefore in patients undergoing aorto-coronary bypass surgery, detrimental changes in the myocardium must be anticipated during the initial phase of cardiopulmonary bypass prior to aortic cross clamping.
A new method of assessing left ventricular (LV) systolic function without terminating assisted circulation (AC) was investigated using a LV volume catheter (conductance catheter) in canine cardiopulmonary bypass (CPB) (Group 1, n = 7) and left heart bypass (LHB) (Group 2, n = 5) models. The hearts were subjected to either 20 min of global ischemia (IS), with a subsequent 80 min of reperfusion under CPB, or regional IS under LHB. Instantaneous LV pressure-volume data acquisitions were repeated during transient (15 sec) acute volume loading without terminating bypass. The relationship between the stroke work (SW), determined as the area of the pressure-volume loop, and the end-diastolic volume (EDV), were highly linear at every study point (mean: r = 0.956-0.986 in Group 1, r = 0.974-0.987 in Group 2). The slopes of SW and EDV (preload recruitable stroke work: PRSW) significantly decreased after IS, in both Group 1 and Group 2. In conclusion, measurement of PRSW without terminating bypass seemed to be useful in evaluating LV systolic function in patients under AC.
Postoperative cardiac patients frequently are mildly hypothermic, yet the influence of hypothermia on left ventricular (LV) contractility has received little attention. To study the possible effects of mild hypothermia on LV function, six pigs were placed on partial right ventricular bypass, the hearts were electrically paced to control heart rate, and myocardial temperature was varied between 34 degrees and 38 degrees C. Using two pairs of orthogonally oriented sonomicrometer crystals in the left anterior descending (LAD) and left circumflex (LCX) distributions, we estimated regional work (the area within LV pressure-area loops) over a range of LV preloads. Diastolic function was assessed by measurement of the time constant of LV pressure decay during isovolumic relaxation. Regional work data were expressed as percentages of baseline (38 degrees C and end-diastolic pressure of 10 mm Hg). To control for preload variations, regional work and time constants were calculated from beats with end-diastolic areas within 0.1% of baseline. Regional work (mean +/- SEM) declined from 85.1 +/- 6.7% at 38 degrees C to 31.9 +/- 4.4% at 34 degrees C. Time constants were prolonged from 44.8 +/- 2.5 msec at 38 degrees C to 61.6 +/- 2.7 msec at 34 degrees C. These data demonstrate a marked depression of LV contractility, even at mild levels of hypothermia that may be encountered clinically after cardiac operations.
The conductance catheter is a promising new instrument for continuously measuring left ventricular (LV) volume. Absolute LV volume (V[t]) is related to uncorrected conductance volume, B(t), according to the equation: V(t) = (1/alpha)(B(t) - alpha Vc). The alpha Vc factor represents parallel-conductance volume due to conducting material outside the LV blood pool, and may be estimated by transiently changing blood conductivity using a bolus injection of hypertonic saline. alpha is the slope in the relation between B(t) and true LV volume. We tested the assumption that alpha Vc and alpha are constant over a range of hemodynamic conditions. We performed multiple hypertonic saline alpha Vc determinations in seven intact dogs during control conditions and subsequent temporary balloon occlusions of inferior vena cava (IVCO), aorta (AO), and pulmonary artery (PAO). We also compared B(t) with simultaneous biplane angiographic LV volume during similar control and intervention conditions. The saline-derived alpha Vc was 76 +/- 2 ml during control and fell significantly by -7 +/- 2 ml during IVCO (p less than 0.001) but not during AO or PAO. According to multiple linear regression analyses, the strongest predictor of saline-derived alpha Vc was uncorrected end-systolic Bes, with a sensitivity coefficient of 0.60 +/- 0.06 ml/ml (p less than 0.001). Angiographically derived alpha Vc showed a similar dependence on Bes, with a coefficient of 0.77 +/- 0.14 ml/ml (p less than 0.001). Angiographically determined alpha also showed significant variation with hemodynamic interventions, largely reflecting an underlying dependence on alpha Vc. The variation in alpha Vc and alpha with LV size may stem from nonlinearity in the B(t)-V(t) relation. Although the conductance catheter provides a useful measure of relative LV volume, measurement of absolute LV volume over a wide hemodynamic range using constant alpha Vc and alpha factors is unrealistic. This result calls into question the current use of this technique for the measurement of the absolute end-systolic--pressure-volume relation.
Although in situ end-systolic pressure-volume relations (ESPVRs) are approximately linear throughout a limited load range, they often yield seemingly "negative" volume axis intercepts (V0) and V0 shifts with inotropic interventions. We tested whether or not these findings could stem from in situ ESPVR nonlinearity, and we examined the physiologic meaning and limitations of linearized ESPVR variables frequently used for assessing contractile state. Continuous left ventricular pressures and volumes were obtained by micromanometer and conductance (volume) catheters in six open-chest dogs. Left ventricular loading was varied throughout a wide range by rapid left atrial hemorrhage into a reservoir. Propranolol and verapamil were administered to reduce inotropic state, with heart rate maintained by atrioventricular sequential pacing. ESPVRs were fit to nonlinear [Pes = a(Ves-V'0)2 + b(Ves-V'0)] and linear (Pes = Ees (Ves-V0)] models. Contractile state was assessed by the slope of the ESPVR at V'0 (b, of nonlinear model) and by two other ESPVR model-independent measures: the slope of the dP/dtmax and end-diastolic volume relation, and the slope of the stroke work and end-diastolic volume relation. ESPVR was frequently curvilinear, and a significant correlation existed between the extent of nonlinearity (a) and contractile state. Volume intercepts derived from linear fits to the high load ESPVR range were mostly negative and were dependent on changes in Ees. V0 estimates derived from the low load portion were positive and relatively insensitive to Ees. Thus, in situ ESPVR displays contractility-dependent curvilinearity. The contractility range throughout which ESPVRs are essentially linear is typical for isolated hearts, but the range represents low values for in situ ventricles. Despite curvilinearity, Ees determined in situ throughout limited load ranges can accurately assess inotropic state; however, comparisons between ESPVRs should consider potential nonlinearity, and if possible, they should be made within similar end-systolic pressure ranges.
Determination of left ventricular pressure-volume relationships in situ ideally requires both a method for easy measurement of multiple pressure-volume loops and a rapid and reversible means of altering load. We report a technique, previously used in animals, that combines conductance catheter volumes and rapid inferior vena caval occlusion to permit routine measurement of calibrated P-V relationships in man for the first time. An 8F volume catheter with a 3F micromanometer tipped pressure catheter placed through its lumen was advanced to the left ventricular apex through a femoral artery. A thermodilution output catheter was placed through a 9F femoral venous sheath and later replaced with an IVC balloon occlusion catheter, through which a 2.5F bipolar wire was advanced for atrial pacing. A specialized data system facilitated collection, editing, and data analysis at the time of cardiac catheterization. Absolute volume calibration required cardiac output measurement and injection of hypertonic saline. IVC occlusion decreased peak left ventricular pressure by 42 +/- 17 (SD) (P less than .001) mm Hg in 15 patients. Endsystolic pressure-volume relationships (ESPVR) were determined with 5-8 cardiac cycles with an average of r2 of 0.94 +/- 0.05 and were generally reproducible. The slope of the ESPVR demonstrated consistency among a group of normal patients (n = 6), and was significantly lower than the slope derived from a group of patients with ventricular hypertrophy (n = 9). We conclude that left ventricular pressure-volume relationships can be easily and repeatedly determined as part of a routine cardiac catheterization in man.
We studied the effects of cardiac cooling by 7 +/- 2 degrees C (SD) from 36 degrees C on both contractility index (Emax) and the relation between O2 consumption per beat (VO2) and systolic pressure-volume area (PVA) of the left ventricle in the excised cross-circulated dog heart preparation. PVA represents the total mechanical energy generated by a contraction. The VO2-PVA relation divides measured VO2 into unloaded VO2 and excess VO2. The slope of the VO2-PVA relation represents inversely the efficiency of the contractile machinery to convert chemical energy from the excess VO2 to total mechanical energy. Cooling is known to decrease myosin ATPase activity (Q10 of 2-3), which in turn is expected to increase the chemomechanical efficiency of cross bridges. Therefore, we expected an increase in the efficiency and hence a decreased slope of the VO2-PVA relation with cooling. The cooling increased Emax by 46 +/- 13% and the time to Emax by 45 +/- 27%. Pacing rate was constant or had to be slightly decreased to avoid arrhythmias with cooling. We found that neither the slope of the VO2-PVA relation nor unloaded VO2 significantly (p greater than 0.05) changed with the cooling. This result contradicts the expected increase in the efficiency with cooling. We conclude that cardiac cooling by 7 degrees C from 36 degrees C does not increase the efficiency of the contractile machinery in excised cross-circulated dog left ventricle.
We assessed the linearity and slope of the left ventricular end-systolic pressure (PES)-volume (VES) relation over a wide range of contractile states in conscious dogs. The animals were instrumented to determine left ventricular volume from ultrasonic left ventricular internal dimensions and measure left ventricular pressure with a micromanometer. Studies were performed 1-2 weeks after instrumentation while the animals were conscious. Contractile state was increased by incremental infusion of dobutamine (0, 2, 4, 6, and 8 micrograms/kg/min i.v.) and decreased by verapamil (10 mg i.v.) given after autonomic blockade. The 44 +/- 11 mm Hg (mean +/- SD) portion of the PES-VES relation generated by bicaval occlusion demonstrated a slight but consistent nonlinearity, apparent as a concavity toward the volume axis. This nonlinearity, present at all inotropic states, did not prevent the PES-VES relation from being well approximated by a straight line (r = 0.984 +/- 0.020, SEE = 2.1 +/- 1.4 mm Hg); furthermore, the slope of the PES-VES line provided a sensitive index of contractile state, progressively increasing with incremental doses of dobutamine and decreasing in response to verapamil. The volume-axis intercept of the linear approximation of the PES-VES relation was 2.9 +/- 3.3 ml less (p less than 0.05) than the volume-axis intercept of the nonlinear quadratic fit. Thus, the linear PES-VES relation, whose slope is sensitive to a wide variety of inotropic states, is a reasonable and useful description of the left ventricle in the range of PES-VES points that can be produced by bicaval occlusion in the conscious dog. However, linear extrapolation of the relation beyond the range of data points may not be accurate.
We evaluated the accuracy of the recently reported technique of estimating intraventricular volume by measurement of intracavitary electrical conductance in six isolated, ejecting, canine left ventricles. Left ventricular volumes were measured directly by a previously validated servosystem that employed an electroconductive balloon placed in the left ventricular cavity. The volume measured continuously by the balloon method (Vbal) was compared with that estimated by the conductance method (Vcath). For this test, the hearts were made to eject and fill physiologically by the use of a previously described computer-simulated arterial loading system. Complex ejection and filling patterns were created by stimulating the atrium mechanically, which resulted in irregular arrhythmatic contractions spanning a wide range of volumes. We found that there was a highly linear relationship (r2 = .982 +/- .014) between Vbal and Vcath: Vcath = 0.82 (+/- .05) Vbal + 26.7 (+/- 11.8) ml. Despite the wide variation in the offset term of this relationship among the different hearts, the offset within a given heart was predicted within 3.5 ml by a previously detailed "dilution" method that is applicable to the heart in situ within a closed thorax. Thus, since the offset term is obtainable in situ, the conductance method provides a signal that is proportional to the actual volume. To determine whether right ventricular volume influenced the accuracy of left ventricular measurement, we compared the relationship between Vcath and Vbal obtained with right ventricular volumes of 0 and 30 ml. Increasing the right ventricular volume shifted the relationship upward by less than 3 ml in the working range.(ABSTRACT TRUNCATED AT 250 WORDS)
It has previously been shown that in the normally ejecting canine left ventricle E(t), the time varying ratio of instantaneous pressure, P(t), to instantaneous volume, V(t), is little affected by end diastolic volume or aortic pressure. This study on an excised, supported canine heart preparation indicates that the thesis on E(t) is also valid for either totally isovolumic or auxobaric beats. Intraventricular volume was measured more accurately than it was in the previous study by a new volumetric system. Regression analysis of the data showed that the instantaneous pressure volume relationship could be approximated by the equation P(t) = E(t) [V(t) - V(d)], where V(d) is an empirical constant, over a wide range of intraventricular volume. Similar E(t) curves were obtained from both isovolumic and auxobaric beats for a given contractile state. When the contractile state of the preparation was enhanced by a constant rate infusion (0.2 μg/min) of norepinephrine or isoproterenol into the coronary artery, the peak magnitude of E(t) increased 63% from 3.6 mm Hg/ml and the time to peak E(t) shortened 10% from 175 msec. It is concluded that the present investigation substantiates an earlier study which established a link between E(t) and the contractile state of the heart.
An eight-electrode conductance catheter previously developed by us and used to determine stroke volume in dogs was applied in human beings and dogs to measure absolute left ventricular volume quantitatively. For calibration we developed the formula V(t) = (1/alpha)(L2/sigma b)G(t) - Vc, where V(t) is time-varying left ventricular volume, alpha is a dimensionless constant, L is the electrode separation, sigma b is the conductivity of blood obtained by a sampling cuvette, and G(t) is the measured conductance within the left ventricular cavity. Vc is a correction term caused by the parallel conductance of structures surrounding the cavity and is measured in two ways. The first method, applicable in the anesthetized animal, consists of temporary reduction of volume to zero by suction. The second method uses a transient change in sigma b by injection of a small bolus of hypertonic saline (dogs) or 10 ml of cold glucose (humans) into the pulmonary artery. The validity of the formula was previously established for the isolated postmortem canine heart. The predicted linearity, slope constant alpha, and accuracy of Vc for the left ventricle in vivo were investigated by comparing the conductance volume data with results from independent methods: electromagnetic blood flow measurement for stroke volume and indicator dilution technique for ejection fraction (dogs), thermal dilution for cardiac output (12 patients), and single-plane cineventriculography for V(t) (five patients). In all comparisons, linear regression showed high correlation (from r = .82 [n = 46] to r = .988 [n = 20]) while alpha, with one exception, ranged from 0.75 to 1.07 and the error in Vc ranged from 0.5% to 16.5% (mean 7%). After positioning of the catheter, no arrhythmias were observed. It is concluded that the conductance catheter provides a reliable and simple method to measure left ventricular volume, giving an on-line, time-varying signal that is easily calibrated. Together with left ventricular pressure obtained through the catheter lumen, the instrument may be used for instantaneous display of pressure-volume loops to facilitate assessment of left ventricular pump performance.
It has been suggested that the increased incidence of ventricular arrhythmias recognized below 30 degrees C might be catecholamine mediated. Elevate catecholamine concentrations have been reported in experimentally induced hypothermia in animals. Plasma concentrations of epinephrine and norepinephrine were measured during profound hypothermia and total circulatory arrest in infants under one year of age undergoing surgical correction of congenital cardiac defects. There was no significant change in either epinephrine or norepinephrine levels during surface cooling to 28 degrees C. Circulatory arrest and exsanguination at 18 degrees C were not associated with a rise in catecholamine levels. However, there was a striking rise in the levels of both epinephrine and norepinephrine with the recommencement of bypass and rewarming. The mean plasma norepinephrine concentration rose from 466 pg/ml (SE +/- 81) at circulatory arrest to 4543 pg/ml (SE +/- 2058) on rewarming bypass (p less than 0.02), while the mean plasma epinephrine concentration rose from 218 pg/ml (SE +/- 54) at circulatory arrest to 3724 pg/ml (SE +/- 1064) on rewarming bypass (p less than 0.02). The plasma catecholamine concentrations fell once cardiopulmonary bypass was discontinued, when the infant's temperature was 37 degrees C. It would, therefore, appear unlikely that the ventricular irritability recognized below 30 degrees C is due to catecholamine excess. The accumulation of catecholamines and/or metabolic products in the infants during circulatory arrest with their subsequent release into the circulation during rewarming may account for the elevation of catecholamine levels during rewarming bypass.
Lowering myocardial temperature increases contractile force, presumably by increasing intracellular calcium content. To study the mechanisms behind this, we compared the effects of some known inotropic interventions with hypothermia on mechanical restitution and post-rest contractile force in isolated guinea-pig papillary muscles. In four groups (n = 6 per group), the effects of: (1) reducing the ability for Na/Ca exchange to extrude Ca2+ (a) by increasing [Na+]i with ouabain or (b) by increasing [Ca2+]o; and (2) activation of calcium channels with Bay-K 8644, were compared with lowering temperature from 37 to 27 degrees C. Normally (at 37 degrees C and 2 mM CaCl2), mechanical restitution could be described by a rapid recovery phase with a time constant between 180 and 220 ms, followed by a slowly decaying phase with a time constant between 5000 and 8000 ms and post-rest contractions (1-10 min rest) were markedly depressed compared to steady-state contractions. Steady-state developed force was markedly increased at 27 degrees C, after 1 microM ouabain, 6 mM CaCl2 or 0.1 microM Bay-K 8644. At 27 degrees C the rapid recovery phase of restitution was delayed while the slowly decaying phase was not affected. Ouabain and increased [Ca2+]o caused elevation of the slowly decaying phase of restitution and markedly attenuated the post-rest depression of developed force, which may be attributed to a reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger. Hypothermia and Bay-K 8644 on the other hand, augmented this post-rest depression. Hence, this study suggests that increased Ca2+ influx due to delayed inactivation of calcium channels may account for the increased developed force during hypothermia rather than reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger.
We studied the effects of mild hypothermia on cardiac contractility in isolated rabbit hearts perfused with Krebs-Henseleit solution according to the technique of Langendorff. Isovolumetric left ventricular pressure (LVP) was measured with a fluid-filled balloon. Hearts were paced after induction of atrioventricular block. At low heart rates ( < 30 bpm) mild hypothermia (cooling to 30 degrees C) induced a 32% increase in LVp (146.5 +/- 10 mm Hg at 30 degrees C vs 110.7 +/- 13 mm Hg at 37 degrees C) but this positive inotropic response was progressively lost by increasing heart rate. At pacing rates > or = 90 bpm, lower systolic LVP, higher diastolic LVP, and lower positive and negative LV dP/dt were obtained in hypothermic (93 +/- 12 mm Hg, 55 +/- 18 mm Hg, 584 +/- 137 mm Hg/s, and 323 +/- 57 mm Hg/s at 210 bpm, respectively) compared to normothermic hearts (123 +/- 4 mm Hg, 10 +/- 4 mm Hg, 1705 +/- 145.5 mm Hg/s, and 1155 +/- 78 mm Hg/s at 210 bpm, respectively.) The duration of mechanical diastole was reduced or suppressed in these hearts. Exposure to the beta-adrenoreceptor agonist, isoproterenol, improved this diastolic dysfunction during hypothermia and pacing at high rates, suggesting that the sarcoplasmic reticulum Ca2+ uptake might be involved. Our data are also consistent with an increase in myofilament Ca2+ sensitivity that is opposed by isoproterenol during hypothermia.
The relative contributions of the different Ca transport systems involved in cardiac relaxation were evaluated at 25 and 35 degrees C in isolated rabbit, ferret, and cat ventricular myocytes during twitches, caffeine-induced contractures in normal Tyrode solution, and caffeine-induced contractures in Na- and Ca-free solution. The time course of intracellular [Ca] decline these contractions in rabbit ventricular myocytes allowed estimates of the relative contributions of the sarcoplasmic reticulum (SR) Ca pump, Na/Ca exchange, sarcolemmal Ca pump, and the mitochondrial calcium uniporter (with the latter two considered together as "slow mechanisms"). The percent contributions of the SR Ca pump, the Na/Ca exchange, and the slow mechanisms were 70, 27 and 3% at 25 degrees C and 74, 23, and 3% at 35 degrees C. Warming from 25 to 35 degrees C decreases twitch contractions in rabbit and ferret myocytes and caffeine-induced contractures in normal Tyrode solution and Na- and Ca-free solution in all species. In contrast, in cat myocytes warming increased twitches, possibly because of a stronger effect of temperature on Ca influx. We conclude that increased temperature accelerates all of the Ca transport systems involved in relaxation. Despite large changes in each Ca transport system with warming, the relative contributions during relaxation remain similar at physiological temperature.
To evaluate the effectiveness of mild hypothermia in postcardiac surgical patients with severe heart failure in spite of conventional medical therapy and the use of intra-aortic balloon pumping (IABP).
Prospective, clinical study.
Teaching hospital.
10 postcardiac surgical patients with severe heart failure despite the use of IABP with massive doses of catecholamine.
Patients underwent mild hypothermia produced by surface cooling (to approximately 34.5 degrees C). Hemodynamic criteria for the induction of hypothermia included a cardiac index (CI) of less than 2.2 L/min/m2 with a pulmonary capillary wedge pressure (PCWP) of up to 18 mmHg despite the use of IABP with massive doses of catecholamine.
After control measurements had been taken at normal core body temperature (37 degrees C), patients were cooled to approximately 34.5 degrees C (using a cooling blanket and gastric lavage with cold water) to decrease tissue oxygen (O2) demand. Patients showed significant improvements in CI (1.9 +/- 0.3 to 2.2 +/- 0.3 L/min/m2), mixed venous O2 saturation, (SvO2; 55 +/- 7 to 64 +/- 6%), and urine output (2.1 +/- 1.1 to 3.4 +/- 2.2 ml/kg/hr). Patients were rewarmed while SvO2 was being monitored. The duration of the hypothermia was 38 +/- 41 hours. Oxygen delivery increased in 8 of the 10 patients, the mean value (+/- SD) for the group rising from 309 +/- 65 ml/min/m2 to 358 +/- 57 ml/min/m2 as temperature was reduced from 36.7 +/- 0.4 degrees C to 34.7 +/- 0.3 degrees C. All patients were successfully weaned from IABP at 140 +/- 107 hours after admission to the intensive care unit.
Mild hypothermia is a simple and useful procedure for improving the circulation of postcardiac surgical patients with severe heart failure despite the use of IABP.
The development of the conductance catheter method has enabled continuous measurement of intraventricular volume in vivo, thus making assessment of pump performance of the heart in vivo possible using pressure-volume analysis. However, this method has not been validated under conditions where pump rate, conductance, viscosity, and temperature of the fluid in the heart chamber is changed as happens in cardiac surgery. To validate the method, pressure-volume data were measured by conductance catheter in a physical model of the human left ventricle. The volume, salinity, viscosity, and temperature of the fluid inside the model were rigorously controlled. The measured pressure-volume data were compared with the actual values to assess the accuracy and dependence of the conductance-measured volumes on salinity, viscosity, temperature, and pump rate. Conductance-measured volumes were not significantly different over a range of heart rates extending from 60 to 100 beats/min, and they were not significantly different over a salinity range of 0.2 to 2 normal saline, a viscosity range of 2.7 to 3.5 centipoise, or over a temperature range of 20 degrees C to 39 degrees C. The percentage errors between actual stroke volumes and conductance-derived volumes were of the order of 10% on average. Our data shows that for a broad range of conditions normally encountered during cardiac surgery, there is no dependence of conductance-measured volume on heart rate, viscosity, temperature, or salinity, provided the correct value of fluid resistivity is used.
We analyzed actomyosin cross-bridge kinetics in human atrial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in atrial than in ventricular human myocardium and lower in failing than in non-failing left ventricular human myocardium. beta-Adrenergic stimulation increased the minimum stiffness frequency by 18 +/- 3% (p < 0.05). Cross-bridge kinetics are temperature-dependent, with a Q10 of at least 2.7.
Dynamic stiffness measurements have revealed acute and chronic alterations of actomyosin cross-bridge kinetics in cardiac muscles of a variety of different animal species. We studied dynamic stiffness in right atrial and left ventricular preparations of non-failing and failing human hearts and tested the influence of the temperature and beta-adrenergic stimulation on cross-bridge kinetics.
Muscle strips were prepared from right atria and left ventricles from human non-failing and failing hearts. After withdrawal of calcium, steady contracture tension was induced by the addition of 1.5 mM barium chloride. Sinusoidal length oscillations of 1% muscle length were applied, with a frequency spectrum of between 0.1 and 60 Hz. Dynamic stiffness was calculated from the length change and the corresponding force response amplitude. The specific minimum stiffness frequency, which indicates the interaction between cross-bridge recruitment and cross-bridge cycling dynamics, was analyzed for each condition: (1) The minimum stiffness frequency was 0.78 +/- 0.04 Hz in left ventricular myocardium and 2.80 +/- 0.31 Hz in right atrial myocardium (p < 0.01) at 27 degrees C. (2) The minimum stiffness frequency was 41% higher in non-failing compared to failing left ventricular human myocardium. (3) Over a wide range of experimental temperatures, the minimum stiffness frequency changed, with a Q10 of at least 2.7. (4) beta-Adrenergic stimulation significantly (p < 0.05) increased the minimum stiffness to 18 +/- 3% higher frequencies and significantly (p < 0.05) lowered contracture tension by 7 +/- 1%.
The contractility of human heart muscle is not only regulated by excitation-contraction coupling but also by modulation of intrinsic properties of the actomyosin system. Acute and chronic alterations of cross-bridge kinetics have been demonstrated, which play a significant role in the physiology and pathophysiology of the human heart.
Defects in myocyte contraction and relaxation are key features of human heart failure. Sodium/calcium exchanger-mediated contribution to contraction and relaxation were separated from other mechanisms [L-type calcium current, sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase] based on voltage, temperature, and selective blockers. Rod-shaped left ventricular myocytes were isolated from failed human explants (n = 29) via perfusion with collagenase-containing Krebs solution. Action potentials using perforated patch and contractions using an edge detector were recorded at 0.5-1.5 Hz in Tyrode solution at 25 degrees C and 37 degrees C. Contraction duration was dependent on action potential (AP) duration at 37 degrees C but not at 25 degrees C, suggesting the role of the exchanger in relaxation and linking myocyte relaxation to the repolarization phase of the AP. Voltage-clamp experiments from -50 to +10 mV for 1,500 ms in Tyrode or Na(+)- and K(+)-free solutions after conditioning pulses triggered biphasic contractions that included a rapid SR-mediated component and a slower voltage-dependent exchanger-mediated component. We used thapsigargin to block the SR, which eliminated the rapid component, and we used an exchanger blocker, Kanebo 7943, which eliminated the slow component. The exchanger was shown to contribute to contraction through reverse-mode exchange, as well as to play a key role in relaxation of human ventricular myocytes.
The effects of hypothermia on ventricular contractility were studied in intact dogs, directly, by attachment of a strain gauge arch to the myocardium and indirectly, by observation of left and right atrial, pulmonary and femoral arterial pressures. Marked increments in heart contractile force and reduction in the rates of contraction and relaxation occurred in all experiments during cooling. Myocardial depression occurred in several experiments, but only at temperatures near 20°C, and in the presence of extreme bradycardia. Total sympathetic block produced by epidural injections of 0.45% procaine solution and large doses of hexamethonium did not prevent development of the increments in heart contractile force, but did further decrease the rates of contraction and relaxation at low body temperatures. Epinephrine administration resulted in pronounced increments in heart contractile force and increases in rates of contraction and relaxation, often in the absence of chronotropic effects. No relationship was found between occurrence of ventricular arrhythmias and magnitude of heart contractile force. Spontaneous occurrence of fused contractions, with apparent summation and incomplete tetanus was observed in several experiments at low body temperatures.
The inotropic consequences of cooling
- Fukunami