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ABSTRACT: Vascular leakage after ischemia-reperfusion (IR) is largely attributed to the destruction of the endothelial barrier and its associated negatively charged glycocalyx. In vitro, sevoflurane attenuates these changes. Therefore, we compared sevoflurane with propofol with regard to the protection of the glycocalyx and the release of negatively charged substances in vivo.
After surgical preparation under midazolam-fentanyl, nine pigs each received either propofol or sevoflurane. Ischemia of 90 min was induced by a balloon catheter in the thoracic aorta. After 120 min of reperfusion, the anesthetics were changed back to midazolam-fentanyl. Five animals, each without aortic occlusion, served as time controls. Blood electrolyte parameters were measured, from which the strong ion gap (SIG) was calculated. Serum heparan sulfate concentrations and immunohistology served as a marker of glycocalyx destruction.
Immediately after reperfusion, SIG increased significantly only in the propofol group (+6.7 mEq/l versus baseline; p < .05), remaining stable in sevoflurane and both time-controlled groups. Initially, heparan sulfate concentration increased comparably in both experimental groups, but after 120 min, it became stable in sevoflurane-anesthetized animals, while increasing further in the propofol group (p < .05).
Unmeasured anions, predictive of negative outcome in previous studies, did not increase significantly in sevoflurane-anesthetized animals. Additionally, there was less heparan sulfate shedding over time, signaling less destruction of the glycocalyx. Therefore, in this in-vivo situation, sevoflurane proves to be superior to propofol in protecting the endothelium from IR injury.
Journal of Investigative Surgery 06/2012; 25(3):162-8. · 1.09 Impact Factor
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ABSTRACT: Functional preload parameters such as stroke-volume variation (SVV) and pulse-pressure variation (PPV) are superior to filling pressures when assessing volume responsiveness in mechanically ventilated patients. This investigation studied their application in the setting of acute myocardial ischemia and reperfusion (I/R).
Experimental animal study in a university laboratory.
Twenty anesthetized and ventilated pigs.
A temporary reduction of preload was obtained by ventilation with a positive end-expiratory pressure of 10 cmH(2)O. Ischemia was induced by temporary occlusion of the left anterior descending coronary artery for 60 minutes and was followed by 30 minutes of reperfusion.
Animals were instrumented with an ultrasonic aortic flow probe to monitor stroke volume (SV) and SVV. Arterial pressure and PPV were recorded with a microtip catheter; left ventricular volume and pressure were registered by a conductance catheter. Respective hemodynamic measurements were made before, during, and after PEEP; before and after the induction of I/R. Eleven animals survived I/R and were analyzed. Before I/R, SVV (r = 0.87, p < 0.001) and PPV (r = 0.75, p < 0.05) during PEEP correlated significantly with relative changes in SV caused by the release of PEEP. Changes in SVV (r = 0.82, p < 0.01) and PPV (r = 0.67, p < 0.05) correlated significantly with relative changes in SV. After I/R, neither the relations between changes in SV to SVV or PPV during PEEP nor the relations between changes in SVV or PPV to changes in SV reached significance.
SVV and PPV did not reflect volume responsiveness in an experimental model of acute myocardial I/R.
Journal of cardiothoracic and vascular anesthesia 11/2010; 25(5):780-3. · 1.06 Impact Factor
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Dirk Bruegger, Gregor I Kemming,
Matthias Jacob,
Franz G Meisner,
Christoph J Wojtczyk,
Kristian B Packert,
Peter E Keipert,
N Simon Faithfull,
Oliver P Habler,
Bernhard F Becker,
Markus Rehm
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ABSTRACT: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis.
Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions.
During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), alpha-ketoglutarate (35.3 microEq/L), fumarate (6.2 microEq/L), sulfate (0.1 mEq/L), and urate (55.9 microEq/L) after shock induction.
Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.
Critical care (London, England) 02/2007; 11(6):R130. · 4.61 Impact Factor
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ABSTRACT: Intermittent positive pressure ventilation and positive end-expiratory pressure (PEEP) affect cardiac preload. Their effect is dependent on chest wall compliance. This study compares the effects of intermittent positive pressure ventilation and PEEP on stroke volume variation and central blood volume during open and closed chest conditions.
Fourteen anesthetized and mechanically ventilated pigs (25-40 kg) were studied. Central blood volume was assessed using global end-diastolic volume and right ventricular end-diastolic volume measured by thermodilution. Further, left and right ventricular stroke volume variations were determined with ultrasonic flow probes placed around the pulmonary artery and ascending aorta, respectively. Measurements were performed during mechanical ventilation without and with PEEP (15 cmH(2)O) in open and closed chest conditions.
With the chest closed mean arterial pressure, cardiac output, stroke volume, global end-diastolic volume, and right ventricular end-diastolic volume were significantly lower when compared to open chest conditions. Concomitantly, right ventricular, but not left ventricular stroke volume variation increased significantly. Applying PEEP led to a significant reduction of cardiac output, stroke volume and right ventricular end-diastolic volume, with a concomitant increase in left and right ventricular stroke volume variation both during open and closed chest conditions (all P-values<0.05).
We conclude that PEEP increases right and left ventricular stroke volume variation both during open and closed chest conditions. The concomitant reduction of right ventricular end-diastolic volume further indicates that PEEP has a preload reductive effect during open chest conditions, too.
European Journal of Cardio-Thoracic Surgery 07/2006; 30(1):90-5. · 2.55 Impact Factor
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ABSTRACT: The pre-ejection period (PEP) has recently been described as a potential parameter for monitoring cardiac preload. This study further investigated the influence of changes in intravascular volume status and the application of positive end-expiratory pressure (PEEP) on the pre-ejection period. In ten pigs, ECG, arterial pressure and stroke volume derived from an aortic flowprobe were registered. Global end-diastolic volume (GEDV) was measured by transcardiopulmonary thermodilution. Total blood volume (TBV) and intrathoracic blood volume (ITBV) were measured by the dye-dilution technique. Measurements were performed during normovolaemic conditions, after volume loading with haemodilution blood (20 ml kg(-1)) and following haemorrhage (30 ml kg(-1)) without PEEP and with PEEP (15 cm H(2)O) applied. Volume loading increased GEDV, ITBV, TBV and SV, whereas PEP remained constant. However, the changes were not significant (P > 0.05). Subsequent haemorrhage significantly decreased GEDV (from 436 to 308 ml), ITBV (from 729 to 452 ml), TBV (from 2,131 to 1,488 ml) (all P-values <0.05), and SV (from 20.7 ml to 14.3 ml, P < 0.001). However, PEP did not change significantly (from 73 to 82 ms, P > 0.05). No correlation between the changes in PEP and changes in any other variable was observed. It is concluded that PEP is not sensitive to the changes in intravascular volume status.
Physiological Measurement 12/2005; 26(6):1033-8. · 1.68 Impact Factor
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Gregor I Kemming,
Franz G Meisner,
Christoph J Wojtczyk,
Kristian B Packert,
Thomas Minor,
Manfred Thiel,
Jochen Tillmanns,
Jens Meier,
Daniel Bottino,
Peter E Keipert,
Simon Faithfull,
Oliver P Habler
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ABSTRACT: Perfluorocarbon (PFC) emulsions are intravascular oxygen therapeutics that temporarily enhance tissue oxygenation in dilutional anemia. However, PFC emulsions are not resuscitation fluids because PFCs only work optimally in the presence of high O2 partial pressure (hyperoxia); moreover, because they have no oncotic potential, dosing limitations prevent their use to permanently replace large hemorrhage volumes. Our objective was to clarify whether in the presence of hyperoxia a conventional colloid therapy supplemented by PFC is more efficacious than colloid alone. To answer this question, 22 anesthetized, ventilated dogs were hemorrhaged to a mean arterial pressure of 45 mmHg and were kept at this level until a metabolic O2 debt of 120 mL kg(-1) body weight had evolved. Hyperoxia was established and dogs were randomly allocated to receive colloid (6% HES, Hydroxy Ethyl Starch shed blood volume) or colloid together with Oxygent (perflubron emulsion, 60%, w/v; Alliance Pharmaceutical Corp., San Diego, CA; single dose, 4.5 mL kg(-1); i.e., 2.7 g PFC kg body weight) in a blinded fashion. Hemodynamic and O2 transport parameters, intestinal mucosal blood flow (microspheres), and O2 partial pressure (MDO-Electrode; Eschweiler, Kiel, Germany) were measured at baseline, in shock, and during 3 h post-therapy. In the presence of hyperoxia, Oxygent improved the amount of physically dissolved O2 in plasma and increased the contribution of physically dissolved O2 to global O2 delivery (P < 0.05) and thus whole body O2 consumption when compared with colloid alone (P < 0.05). As a result, Oxygent reduced intestinal mucosal hypoxia and global O2 debt within the first hour post-therapy (P < 0.05). We conclude that under hyperoxic conditions, fluid resuscitation supplemented by Oxygent was more efficacious than colloid and hyperoxia alone. PFC temporarily enhanced intestinal mucosal tissue oxygenation during resuscitation.
Shock 10/2005; 24(3):245-54. · 2.85 Impact Factor
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ABSTRACT: Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs.
Twenty-two pigs (29 [23, 31] kg body weight [first, third interquartile]; tracheostomy) were anesthetized and mechanically ventilated. In the endotoxin (n = 8) and perfluorohexan groups (n = 7), we administered endotoxin of Escherichia coli 111:B4, 1 mg.kg . h for 1 h and 10 microg.kg.h for 5 h in consecutive order. In the perfluorohexan group, inhalation of the test drug was started 2 h 30 min after the start of the intravenous endotoxin and terminated after 30 min. In a control group (n=7), animals were instrumented and observed over time without further intervention. Oxygenation function was assessed from oxygen partial pressures (Po2, blood gases) and calculated shunt fraction. Respiratory compliance was calculated from airway pressure and tidal volume. Measurements were performed before and every hour during endotoxin infusion.
After 6 h of endotoxin, gas exchange and pulmonary compliance were deteriorated in the endotoxin group (Pao2: 184 [114, 289] vs. 638 [615, 658] mmHg, pulmonary shunt fraction: 30 [23, 38] vs. 4 [3, 6]%, respiratory compliance: 12 [11, 14] vs. 22 [19, 23] ml/mbar; P < 0.05, endotoxin vs. control). Inhalation of vaporized perfluorohexan did not improve Pao 2 (107 [60, 221] mmHg), pulmonary shunt fraction (32 [26, 58]%), or respiratory compliance (14 [10, 17] ml/mbar) when compared with intravenous endotoxin (not significant, perfluorohexan vs. endotoxin).
Inhalation of vaporized perfluorohexan does not improve pulmonary gas exchange or respiratory compliance in endotoxin-induced porcine lung injury.
Anesthesiology 09/2005; 103(3):585-94. · 5.36 Impact Factor
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ABSTRACT: Background: Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs.
Anesthesiology 08/2005; 103(3):585-594. · 5.36 Impact Factor
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ABSTRACT: Ventilation with 100% oxygen (Fio(2) 1.0; hyperoxic ventilation; HV) as an alternative to red blood cell transfusion enables survival in otherwise lethal normovolemic anemia. The aim of the present study was to investigate whether HV as a supplement to fluid infusion therapy could also restore adequate tissue oxygenation and prevent death in otherwise lethal hemorrhagic shock. In 14 anesthetized pigs ventilated on room air (Fio(2) 0.21), hemorrhagic shock was induced by controlled withdrawal of blood (target mean arterial pressure 35-40 mmHg) and maintained for 1 h. Subsequently, the animals were partially fluid-resuscitated (i.e., replacement of lost plasma volume) either with hydroxyethyl starch (6% HES, 200/0.5) alone (G 0.21) or with HES supplemented by HV (G 1.0). After completion of partial fluid resuscitation, all animals were followed up for the next 6 h. Five of seven animals of G 0.21 died within the 6-h observation period (i.e., 6-h mortality 71%). Death was preceded by a continuous increase of the serum concentrations of arterial lactate and persistent tissue hypoxia. In contrast to that, all animals of G 1.0 survived the 6-h observation period without lactic acidosis and with improved tissue oxygenation (i.e., 6-h mortality 0%; G 0.21 versus G 1.0 P < 0.05). In anesthetized pigs submitted to lethal hemorrhagic shock, the supplementation of partial fluid resuscitation with HV improved tissue oxygenation and enabled survival for 6 h.
Shock 09/2004; 22(3):240-7. · 2.85 Impact Factor
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Gregor I Kemming,
Joanne B Messick,
Georg Enders,
Mihaly Boros,
Baerbel Lorenz,
Silvia Muenzing,
Hille Kisch-Wedel,
Werner Mueller,
Agnes Hahmann-Mueller,
Konrad Messmer,
Eckart Thein
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ABSTRACT: Mycoplasma haemocanis (formerly Haemobartonella canis) is a red blood cell parasite that causes disease mainly in immunosuppressed and splenectomized dogs. Clinical outbreak of the disease resulted in failure of a large experimental project. We aimed to identify whether M. haemocanis has increased prevalence in kennel-raised dogs. In a prospective study, we compared the prevalence of M. haemocanis in whole blood (anti-coagulated by use of EDTA) collected from pet dogs (University of Illinois, Urbana Champaign, Ill.; n = 60) with that in blood from dogs raised in three distinct kennels in western Europe (WE; n = 23), eastern Europe (EE; n = 20), and North America (NA; n = 20). Screening included antibody testing and microscopy of blood smears. The presence of M. haemocanis was identified using a polymerase chain reaction (PCR) assay for specific DNA of the organism. None of the pet dogs (0%) was test positive for M. haemocanis DNA. Mycoplasma haemocanis was found in dogs tested at all of the kennels. Infection rate in the three kennels was 30, 35, and 87%, respectively (all P < 0.001 versus control, chi2-test). Latent infection with M. haemocanis was not a single observation in kennel-raised dogs. Prevalence may be higher than that in a pet dog population. The potential exists for these latent infections to adversely affect or confound research results.
Comparative medicine 09/2004; 54(4):404-9. · 1.05 Impact Factor
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ABSTRACT: Acute normovolemic hemodilution reduces the circulating erythrocyte mass and, thus, the hemoglobin concentration. After extreme acute normovolemic hemodilution to the critical hemoglobin concentration (Hbcrit), oxygen demand of the tissues is no longer met by oxygen supply, and death occurs with increasing oxygen debt. The aim of the current study was to investigate whether ventilation with 100% oxygen (fraction of inspired oxygen [FiO2] = 1.0; hyperoxic ventilation) initiated at Hbcrit could restore adequate tissue oxygenation and prevent death.
Fourteen anesthetized pigs ventilated with room air (FiO2 = 0.21) were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual Hbcrit was reached. Hbcrit was defined as the onset of oxygen supply dependency of oxygen consumption and was identified with indirect calorimetry. For the next 6 h, animals were either ventilated with an FiO2 of 0.21 (n = 7) or an FiO2 of 1.0 (n = 7).
All animals in the 0.21 FiO2 group died within the first 3 h at Hbcrit (i.e., 6-h mortality 100%). Death was preceded by an increase of serum concentrations of lactate and catecholamines. In contrast to that, six of the seven animals of the 1.0 FiO2 group survived the complete 6-h observation period without lactacidosis and increased serum catecholamines (i.e., 6-h mortality 14%; FiO2 0.21 vs. FiO2 1.0, P < or = 0.05). After 6 h at Hbcrit, the FiO2 was reduced from 1.0 to 0.21, and five of the six animals died within the next 3 h.
In anesthetized pigs submitted to lethal anemia, hyperoxic ventilation enabled survival for 6 h without signs of circulatory failure.
Anesthesiology 02/2004; 100(1):70-6. · 5.36 Impact Factor
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ABSTRACT: Background: Gastric tonometry is intended to reveal alterations in splanchnic perfusion and oxygenation. Based on the tonometric measurement of gastric mucosal partial pressure of carbon dioxide (pCO2) and the simultaneous determination of arterial blood gas parameters (bicarbonate concentration [HCO3-], pH and pCO2), several parameters can be calculated. Aims: To identify the most suitable tonometric parameter [gastric mucosal pH (pHi), intramucosal pCO2 (piCO2), the difference between tonometric and arterial pCO2 concentrations (pCO2 gap), [H+] gap] that reliably reflects gastric hypoperfusion and hypoxia during severe haemorrhagic shock. Design: Randomised, controlled experimental study. Methods: An artificial stenosis of the left anterior descending coronary artery (LAD) was induced. Subsequently, the animals were haemorrhaged to a mean arterial pressure of 45 mmHg, which was maintained for 60 min. Measurements and main results: Tonometric measurements were performed in 17 land-race pigs before and after induction of LAD stenosis and after haemorrhagic shock. P values obtained using the Wilcoxon signed-rank testing were used to compare the level of significance for the tonometric parameters and the corresponding arterial blood gas values [arterial pCO2 (paCO2), [HCO3-], arterial pH (pHa)]. While induction of critical coronary stenosis did not provoke any changes, all parameters changed significantly during haemorrhagic shock. The lowest P value was found for pHi (P=0.00013) followed by [H+ gap] (P=0.0005). P values higher by a factor of ten were found for pCO2 gap (P=0.00119) and were highest for piCO2 (P=0.00562). P values of the corresponding arterial blood gas parameters were lower by a factor of ten than the P value of piCO2. Conclusion: pHi, pCO2 gap and [H+] gap are considerably influenced by changes of systemic arterial blood gas values. This is demonstrated by lower P values of the corresponding arterial blood gas values in comparison with piCO2. Therefore pHi, pCO2 gap and [H+] gap seem to indicate more likely systemic changes, whereas piCO2 appears to reflect disturbances of regional gastric tissue perfusion and oxygenation more reliably than any other derived tonometric parameter.
Langenbeck s Archives of Surgery 01/2001; 386(5):333-338. · 1.81 Impact Factor
