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Captopril in acute myocardial infarction: Beneficial effects on infarct size and arrhythmias
Abstract
It is known from experiments that angiotensin converting enzyme (ACE) inhibitors can limit infarct size. We examined the effect in patients.
In a prospective, randomized, placebo-controlled double blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 hours and 18 hours from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex.
The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV) (p < 0.05). The number of ventricular premature beats at 24 hours from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred 7 times in the placebo group, but did not occur in the captopril group. The creatine kinase (CK) infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). The mean arterial pressure was reduced by 12 mmHg with captopril treatment.
The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.
... In this respect, our findings agree with those obtained with captopril (11,36,37) and ramipril (10), which also significantly reduced the incidence and duration of ventricular fibrillation in isolated rat hearts. In patients, early treatment with captopril (starting 2-18 hours after the onset of symptoms of infarction) also decreased the incidence of PVCs, pathological Q waves, and ventricular fibrillation (38). Ventricular fibrillation was not observed in the infarcted rats. ...
... Furthermore, histological examinations of hearts from untreated and treated rats showed complete transmural infarcts, as verified by staining with sirius red (Fig. 5). The ACE inhibitor captopril also reduces the incidence of pathological Q waves after coronary occlusion in rats (41) and humans (38); however, the effects of ACE inhibitors on infarct size are controversial. In this regard, some studies have found no difference between those treated with ACE inhibitors and untreated groups (3,42,43), whereas others have shown a reduction in infarct size (2). ...
Background: Various angiotensin-converting enzyme inhibitors are known to improve heart function and prolong survival in patients and animals after myocardial infarction. Because myocardial infarction is known to induce arrhythmias, this study tested the hypoth esis that early treatment with the angiotensin-converting enzyme inhibitor imidapril reduces mortality during acute myocardial infarction because of protective effects against arrhythmogenesis.
Methods and Results: Rats were randomly divided into four groups: sham control, myocar dial infarction, sham plus imidapril, and myocardial infarction plus imidapril. Myocardial infarction was produced by ligation of the left anterior descending coronary artery. Treated rats received imidapril (1 mg/kg/day) through a gastric tube beginning 1 hour after coronary occlusion; control rats received tap water. Electrocardiograms (ECGs) were recorded 1, 3, 7, and 21 days postocclusion. Infarct size and scar weight were determined at 21 days in the myocardial infarction groups with and without imidapril treatment. ECGs of untreated rats showed ST-segment changes, abnormal Q waves, premature ventricular complexes, and QTc prolongation 1-21 days after coronary occlusion. Total mortality in 21 days averaged 35% in untreated rats; mortality within 48 hours was 30%. On the other hand, imidapril-treated rats showed fewer ST-segment changes, fewer abnormal Q waves, and a decreased inci dence of premature ventricular complexes after coronary occlusion; the ST-segment and QTc interval returned to basal values within 1 week after occlusion. Imidapril treatment did not affect the ECG pattern in sham-treated control animals. Total mortality in the imidapril- treated group in 21 days after infarction was 22.5%; mortality within 48 hours was 20% (P < .05 compared with the untreated infarction group). Infarct size and scar weight caused by coronary occlusion did not differ in the untreated and imidapril-treated groups. Conclusions: Early treatment with imidapril markedly decreases mortality in rats after acute myocardial infarction. The lower mortality is not associated with a decrease in infarct size but is consistent with a protective effect of the drug against arrhythmogenesis.
... В экспериментах на животных ангиотензин II стимулировал развитие атеросклероза на фоне гиперхолестеринемии. Подавление активности РАС путем введения ИАПФ или антагонистов рецепторов ангиотензина II (АРА), напротив, препятствует развитию атеросклероза у животных [19][20][21][22]. ...
... Исследование было прекращено раньше времени из-за явного преиму-щества раннего назначения ИАПФ. Помимо уменьшения размеров ИМ, уменьшалась выраженность ремоделирования левого желудочка; его систолическая функция оказывается лучше, чем при более позднем назначении терапии [20][21][22]43]. Результаты мета-анализа, включавшего более 100000 больных, показали, что ИАПФ по сравнению с плацебо достоверно снижают смертность в течение 30 дней после острого ИМ (7,1% против 7,6%). ...
The role of angiotensin II in pathogenesis of cardiovascular diseases is discussed. Angiotensin II participates in development of acute myocardial infarction (MI) in patients with atherosclerosis. It contributes to inflammation of vessel intimae, oxidative stress, cells apoptosis, matrix remodeling, has pro-thrombosis action, promotes MI expansion and post-MI remodeling. Angiotensin converting enzyme (ACE) inhibitors reduce mortality and improve prognosis of patients with acute MI. In patients with ischemic heart disease including patients after MI ACE inhibitors reduce mortality, risk of repeated MI as well as improve quality of life.
... The results of the confounding factor analysis showed that there was no relationship between ACEI / ARB, beta-blockers and anticoagulant to GLS. In contrast to the results of this study, Bussmann et al. 31 giving intravenous captopril at a dose of 1.5 to 2 mg/hour for 18 hours were able to limit the extent of infarction. In this study, the administration of ACEI or ARB did not affect GLS values may be because subjects who received the therapy had a long ischemia time and patients who had just received 1 dose of ACEI or ARB and with inadequate doses. ...
Background: Coronary heart disease (CHD) is a problem that contributes to morbidity and mortality. Acute myocardial infarction with ST-Segment Elevation Myocardial Infarction (STEMI) is the most common manifestation of CHD. Cardiac muscle damage caused by STEMI is dynamic. The longer coronary is occluded, the area of infarction will be greater than cause biomechanical changes in the myocardium. Speckle Tracking Echocardiography (STE) through a longitudinal strain parameter is a technique of assessing myocardial deformation and predicting the infarct area immediately after reperfusion therapy. Method: This study was an analytic observational study with a cross-sectional method. Subjects were STEMI patients who were successfully reperfused and fulfilled the inclusion and exclusion criteria. Transthoracic echocardiography was performed within 12 hours after reperfusion. Strain analysis was done offline at the work station. A normality test was performed to determine the type of correlation test used. The influence of confounding factors was analyzed by bivariate and multivariate. A value of p <0.05 was said to be statistically significant. Results: There were 43 subjects, ischemia time and global longitudinal starin (GLS) were obtained. A normality test using Shapiro Wilk revealed that data distribution of the two variables was abnormal. The Spearman correlation test was used to assess the relationship between the two variables and found a negative correlation between the time of ischemia and GLS (r = -0.546; p = 0.000). Bivariate and multivariate analyses were performed to assess the influence of confounding factors. From the multivariate test, it was found that ischemia time was an independent factor influencing GLS value (p = 0.002). Conclusion: There is a negative correlation between ischemia time and left ventricular GLS in STEMI patients who were successfully reperfused (r = -0.546; p = 0.000).
... The possibility of the involvement of angiotensin II in the genesis of ventricular arrhythmias was explored by treatment of ischemic hearts upon either angiotensin converting enzyme inhibition or angiotensin II receptor blockade. In this regard, several angiotensin converting enzyme inhibitors including captopril, ramipril and imidapril, which prevent the formation of angiotensin II, have been reported to reduce various types of arrhythmias due to ischemic heart disease [61][62][63][64][65]. The data for the electrocardiographic changes at 21 days after myocardial infarction [66] in the untreated and imidapril-treated animals are shown in Table 5. ...
Ventricular arrhythmias, mainly lethal arrhythmias, such as ventricular tachycardia and fibrillation, may lead to sudden cardiac death. These are triggered as a result of cardiac injury due to chronic ischemia, acute myocardial infarction and various stressful conditions associated with increased levels of circulating catecholamines and angiotensin II. Several mechanisms have been proposed to underlie electrical instability of the heart promoting ventricular arrhythmias; however, oxidative stress which adversely affects ion homeostasis due to changes in the ion channel structure and function, seems to play a critical role in eliciting different types of ventricular arrhythmias. Prevention or mitigation of the severity of ventricular arrhythmias due to antioxidants has been indicated as the fundamental contribution in the field of preventive cardiology; however, novel interventions have to be developed for greater effectiveness and specificity in attenuating the adverse effects of oxidative stress. In this review, we have attempted to discuss proarrhythmic effects of oxidative stress differing in time and concentration dependence and highlight a molecular and cellular concept how it alters cardiac cell automaticity and conduction velocity sensitizing the probability of ventricular arrhythmias with resultant sudden cardiac death due to ischemic heart disease and other stressful situations. It is concluded that pharmacological approaches targeting multiple mechanisms besides oxidative stress might be more effective in the treatment of ventricular arrhythmias than current antiarrhythmic therapy.
... For example, bradykinin is degraded by the angiotensin-converting enzyme (ACE) and administration of ACE inhibitors; increasing bradykinin levels have decreased both infarction size and arrhythmias in humans. 74 Receptor activation by triggers initiates intracellular pathways, presumably involving protein kinase C in the rat. 71,75 ATP-sensitive Kþ channels (K ATP ) channels, especially the mitochondrial ones, have been suggested as the end effector in IPC in many species, including rats, 76 potentially explaining the antiarrhythmic effect of K ATP channel openers. ...
A number of animal models have been designed in order to unravel the underlying mechanisms of acute ischemia-induced arrhythmias and to test compounds and interventions for antiarrhythmic therapy. This is important as acute myocardial infarction (AMI) continues to be the major cause of sudden cardiac death, and we are yet to discover safe and effective treatments of the lethal arrhythmias occurring in the acute setting. Animal models therefore continue to be relevant for our understanding and treatment of acute ischemic arrhythmias. This review discusses the applicability of the rat as a model for ventricular arrhythmias occurring during the acute phase of AMI. It provides a description of models developed, advantages and disadvantages of rats, as well as an overview of the most important interventions investigated and the relevance for human pathophysiology.
... Animal studies indicate that ACE-I therapy administered prior to experimental MI can result in both reduced myocardial infarct size and reduced incidence of reperfusion ventricular arrhythmias. [12][13][14][15][16][17] In our study, we retrospectively examined the outcome of MI in two separate cohorts of patients who either did or did not receive chronic ACE-I therapy prior to the index event. We sought to determine whether patients receiving prior ACE-I therapy showed any differences in clinical outcome compared with patients who did not receive it. ...
Angiotensin-converting enzyme inhibitor (ACE-I) therapy reduces complications of acute myocardial infarction (MI) even when the therapy is started very early after an acute event. This study sought to determine whether administration of ACE-I therapy prior to acute MI is related to subsequent patient morbidity and mortality.
Chart review of 318 consecutive patients admitted between September 1995 and December 1996 with a diagnosis of acute MI. Outcome data were compared between patient groups receiving ACE-I therapy prior to infarction and those who were not.
Sixty-four patients (20%) were receiving prior ACE-I therapy. They experienced smaller MIs, as determined by peak creatine kinase elevation (1066 +/- 134 vs. 1510 +/- 95 IU; p < 0.05), and fewer Q-wave infarctions (p < 0.05) than did patients who were not receiving prior treatment. The severity of coronary artery disease, defined by an angiographic score, was similar for the two groups. Mortality rates, including patients resuscitated from ventricular fibrillation, were similar within the first 72 hours of admission (3% vs. 2%; p = NS), but patients receiving prior ACE-I therapy showed a greater long-term in-hospital mortality rate (14% vs. 5%; p < 0.05) related to more heart failure deaths. Multivariate logistic regression analysis identified age, treatment with digoxin prior to acute MI, and left ventricular ejection fraction after infarction, but not ACE-I therapy taken prior to infarction, as significant independent predictors of mortality and combined morbidity and mortality.
In a group of patients experiencing an acute MI, those receiving prior ACE-I therapy were more likely to sustain fewer transmural MIs and smaller infarcts. Chronic ACE-I therapy may have cardioprotective effects during acute myocardial ischemia.
BACKGROUND: Angiotensin-converting enzyme inhibitor (ACE-I) therapy reduces complications of acute myocardial infarction (MI) even when the therapy is started very early after an acute event. This study sought to determine whether administration of ACE-I therapy prior to acute MI is related to subsequent patient morbidity and mortality.
Of 350 consecutive patients without previous symptoms of coronary artery disease, admitted to hospital with an acute myocardial infarction, 109 of them (31%) reported a history of previous hypertension. Hypertensive patients were older than their normotensive counterparts, more of them were females, and thrombolytic treatment was administered to significantly fewer. Blood pressure values at admission to hospital were higher in hypertensive patients; this difference was significant in hypertensive males. Altogether 44 out of 49 female (90%) and 42 out of 60 male hypertensive patients (70%) reported using antihypertensive medication. A previous history of hypertension did not change infarct size as assessed by peak enzyme levels, neither in the bivariate nor in the multivariate analysis. In contrast to this, the adjusted odds ratio for developing a non-Q-wave infarct was 2.51 (p = 0.003), i.e. the chance of developing a non-Q-wave infarct in hypertensives was increased by 151%. Thus, in spite of similar inf...
In patients with acute myocardial infarction, timely reperfusion is essential to limit infarct size. However, reperfusion also adds to myocardial injury. Brief episodes of ischaemia/reperfusion in the myocardium or on organ remote from the heart, before or shortly after sustained myocardial ischaemia effectively reduce infarct size, provided there is eventual reperfusion. Such conditioning phenomena have been established in many experimental studies and also translated to humans. The underlying signal transduction, that is the molecular identity of triggers, mediators and effectors, is not clear yet in detail, but several extracellular signalling molecules, such as adenosine, bradykinin and opioids, have been identified to contribute to cardioprotection by conditioning manoeuvres. Several trials have attempted the translation of cardioprotection by such autacoids into a clinical scenario of myocardial ischaemia and reperfusion. Adenosine and its selective agonists reduced infarct size in a few studies, but this benefit was not translated into improved clinical outcome. All studies with bradykinin or drugs which increase bradykinin's bioavailability reported reduced infarct size and some of them also improved clinical outcome. Synthetic opioid agonists did not result in a robust infarct size reduction, but this failure of translation may relate to the cardioprotective properties of the underlying anaesthesia per se or of the comparator drugs. The translation of findings in healthy, young animals with acute coronary occlusion/reperfusion to patients of older age, with a variety of co‐morbidities and co‐medications, suffering from different scenarios of myocardial ischaemia/reperfusion remains a challenge.
Linked Articles
This article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8
We describe a novel model of myocardial infarction (MI) in rats induced by percutaneous transthoracic low-energy laser-targeted photodynamic irradiation. The procedure does not require thoracotomy and represents a minimally invasive alternative to existing surgical models. Target cardiac area to be photodynamically-irradiated was triangualted from the thoracic X-ray scans. The acute phase of MI was histopathologically characterized by the presence of extensive vascular occlusion, hemorrhage, loss of transversal striations, neutrophilic infiltration and necrotic changes of cardiomyocytes. Consequently, damaged myocardium was replaced with fibrovascular and granulation tissue. The fibrotic scar in the infarcted area was detected by computer tomography imaging. Cardiac troponin I (cTnI), a specific marker of myocardial injury was significantly elevated at 6h (41±6 ng/mL, n=4, P<0.05 versus baseline), and returned to baseline after 72h. Triphenyltetrazolium chloride staining revealed transmural anterolateral infarcts targeting 25±3% of the left ventricle at day 1 with decrease to 20±3% at day 40 (n=6 for each group, P<0.01 versus day 1). Electrocardiography (ECG) showed significant ST-segment elevation in the acute phase with subsequent development of a pathological Q-wave and premature ventricular contractions in the chronic phase of MI. Vectorcardiogram analysis of spatio-temporal electrical signal transduction revealed changes in inscription direction, QRS loop morphology, and redistribution in quadrant areas. The photodynamically induced MI in n=51 rats was associated with 12% total mortality. Histological findings, ECG abnormalities, and elevated cTnI levels confirmed the photosensitizer-dependent induction of MI after laser irradiation. This novel rodent model of MI might provide a platform to evaluate new diagnostic or therapeutic interventions.
Objective: To investigate whether patients who are using angiotensin converting enzyme (ACE) inhibitors at the onset of infarction develop smaller infarcts, as assessed by peak enzyme levels, and to what extent this is associated with more non-Q-wave infarcts.
Design and Setting: Observational study set in coronary care units in Norway.
Patients: 752 patients discharged alive with an established diagnosis of acute myocardial infarction (AMI), of whom 410 were not given thrombolytic treatment at entry.
Methods: We obtained data from case records and by personally interviewing patients. In addition to premorbid status and clinical data, we obtained information on drugs used before entry to hospital. Infarct size (in patients not given thrombolytic treatment) and localisation were compared between users and non-users of ACE inhibitors, and subsequently subjected to multivariate analysis.
Results: A propensity towards non-Q-wave infarctions was seen in patients with a history of hypertension and angina pectoris and in those who had used aspirin (acetylsalicylic acid) before admission to hospital [adjusted odds ratios of 1.71 (p = 0.005), 1.54 (p = 0.020) and 1.82 (p= 0.004), respectively]. Non-Q-wave infarctions were not associated with the use of ACE inhibitors in multivariate analysis. In the multivariate analysis, the use of ACE inhibitors was associated with reduced peak plasma creatine kinase (CKmax) [730 U/L, p < 0.001] and lactate dehydrogenase (LDmax) [795 U/L, p = 0.044] levels, withsimilar effects of aspirin and calcium antagonists, against a mean level of 1056 U/L (CKmax) and 906 U/L (LDmax) in non-users of these drugs.
Conclusion: Intake of ACE inhibitors prior to an AMI may contribute to a reduction of infarct size.
The protective effect and mechanism of action of the angiotensin-converting enzyme inhibitor (ACE-I) captopril was investigated in organelles from ischemic myocardial cells in a canine coronary ligation model. Sarcoplasmic reticulum (SR) and mitochondrial fractions were extracted from ischemic and nonischemic myocardial cells from captopril- and saline-treated (control) hearts. Heart rate, cardiac output, and right ventricular systolic blood pressure were similar in the captopril-treated and control groups. Left ventricular systolic blood pressure (LVPs) decreased gradually to 89% of the baseline value after captopril administration, and to 78% of the baseline value after ligation. Ca-ATPase activity in the SR, the respiratory control ratio (RCR) in the mitochondria, and dinitrophenol (DNP)-stimulated ATPase activity were significantly higher in ischemic myocardium from the captopril-treated group than from the saline-treated (control) group. The SH group content of both organelles was higher in the captopril-treated group. Our results suggest that, in addition to their hemodynamic effects, ACE-I agents containing SH groups protect the myocardium from ischemic damage by preventing enzyme oxidation.
To examine the effects of early angiotensin-converting enzyme (ACE) inhibitor therapy after myocardial infarction on infarct expansion in an experimental rat model.
ACE inhibitor therapy within 24 h of acute myocardial infarction (AMI) reduces mortality by unknown mechanism(s).
Rats underwent permanent coronary artery occlusion. A treated group received enalapril (1.9+/-0.2 mg/kg) daily in drinking water beginning 2 h after coronary artery occlusion, a time too late to reduce infarct size. Rats were sacrificed 2 days or 2 weeks after myocardial infarction. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis.
Infarcts in the control group expanded between 2 days and 2 weeks after myocardial infarction (expansion index 0.7+/-0.1 versus 2.5+/-0.4, P< 0.05). However, infarct expansion remained unchanged in the enalapril group between 2 days and 2 weeks after myocardial infarction (expansion index 0.8+/-0.1 versus 1.3+/-0.1, NS). Two weeks after myocardial infarction, the enalapril group had fewer expanded infarcts than the control group (expansion index 1.3+/-0.1 versus 2.5+/-0.4, P< 0.05). While left ventricular volume increased in the control group between 2 days and 2 weeks after myocardial infarction (0.17+/-0.01 ml versus 0.36+/-0.03 ml, P< 0.05), it remained constant in the enalapril group (0.22+/-0.02 ml versus 0.25+/-0.03 ml, NS). Two weeks after myocardial infarction, the left ventricles were larger in the control group than in the enalapril group (0.36+/-0.03 ml versus 0.25+/-0.03 ml, P< 0.05).
Treatment with enalapril initiated 2 h after AMI prevented left ventricular dilation by limiting infarct expansion. This may explain the mechanism by which ACE inhibitor therapy started within 24 h of an AMI improves survival 5-6 weeks after infarction.
Estimate the effect of angiotensin converting enzyme (ACE) inhibitors on the risk of sudden cardiac death (SCD) following myocardial infarction (MI).
Trials in post-MI patients have shown that ACE inhibitor therapy reduces mortality. However, the effect on SCD as a mechanism has not been clarified.
Trials of ACE inhibitor therapy following MI reported between January, 1978 and August, 1997 were identified. Studies were included if they met the following criteria: 1) randomized comparison of ACE inhibitor to placebo within 14 days of MI; 2) study duration/blinded follow-up of > or =6 weeks; 3) the number of deaths and modes of death were reported or could be obtained from the investigators.
We identified 374 candidate articles, of which 15 met the inclusion criteria. The 15 trials included 15,104 patients, 2,356 of whom died. Most (87%) fatalities were cardiovascular and 900 were SCDs. A significant reduction in SCD risk or a trend towards this was observed in all of the larger (N > 500) trials. Overall, ACE inhibitor therapy resulted in significant reductions in risk of death (random effects odds ratio [OR] = 0.83; 95% confidence interval [CI] 0.71-0.97), cardiovascular death (OR = 0.82; 95% CI 0.69-0.97) and SCD (OR = 0.80; 95% CI 0.70-0.92).
This analysis is consistent with prior reports showing that ACE inhibitors decrease the risk of death following a recent MI by reducing cardiovascular mortality. Moreover, this analysis suggests that a reduction in SCD risk with ACE inhibitors is an important component of this survival benefit.
Individually, both late reperfusion and early angiotensin converting enzyme (ACE) inhibitor treatment prevent infarct expansion after acute myocardial infarction.
To examine the effect and mechanism of early post-myocardial infarction ACE inhibitor treatment, when used in combination with late coronary artery reperfusion, on infarct expansion.
Sprague-Dawley rats underwent 8 h of coronary occlusion followed by permanent reperfusion. The treatment group received enalapril, started 1 h after coronary occlusion and continued for 13 days. A control group received placebo. Two weeks after acute myocardial infarction, hemodynamic, morphometric and histologic analyses were performed.
Hemodynamic parameters were similar in both groups (P = NS). Infarct size was similar in the ACE inhibitor and placebo treatment groups (44 +/- 4% compared with 39 +/- 4%, P = NS). Septal thickness was also similar in the two groups (2.8 +/- 0.3 mm compared with 2.7 +/- 0.3 mm, P = NS). The ACE inhibitor-treated group had thicker infarcts than those in the placebo-treated group (0.93 +/- 0.07 mm compared with 0.76 +/- 0.04 mm, P < 0.05) and these infarcts were less expanded (expansion index 1.17 +/- 0.12 compared with 1.57 +/- 0.12, P < 0.05). ACE inhibitor treatment was associated with hypertrophy of viable myocytes within the scar compared with placebo treatment (cell diameter 11.1 +/- 0.5 microns compared with 8.9 +/- 0.4 microns, P < 0.01).
Early post-myocardial infarction ACE inhibitor treatment enhances the benefits of late coronary reperfusion on infarct expansion. The benefits may be related to hypertrophy of still-viable myocytes within the infarcted zone.
Of 350 consecutive patients without previous symptoms of coronary artery disease, admitted to hospital with an acute myocardial infarction, 109 of them (31%) reported a history of previous hypertension. Hypertensive patients were older than their normotensive counterparts, more of them were females, and thrombolytic treatment was administered to significantly fewer. Blood pressure values at admission to hospital were higher in hypertensive patients; this difference was significant in hypertensive males. Altogether 44 out of 49 female (90%) and 42 out of 60 male hypertensive patients (70%) reported using antihypertensive medication. A previous history of hypertension did not change infarct size as assessed by peak enzyme levels, neither in the bivariate nor in the multivariate analysis. In contrast to this, the adjusted odds ratio for developing a non-Q-wave infarct was 2.51 (p=0.003), i.e. the chance of developing a non-Q-wave infarct in hypertensives was increased by 151%. Thus, in spite of similar infarct size in normotensive and hypertensive patients, a relative smaller proportion of the probably hypertrophied left ventricular wall developed necrosis in the hypertensive population. The propensity towards non-Q-wave infarctions may contribute to the observed less use of fibrinolytic drug treatment in the presently observed patients with hypertension.
The development of angiotensin-converting enzyme inhibitors (ACE inhibitors) has been one of the most remarkable stories in the treatment of cardiovascular diseases. Angiotensin converting enzyme inhibitors have several acute and sustained hemodynamic effects that are beneficial in the presence of left ventricular (LV) dysfunction. They increase cardiac output and stroke volume and reduce systemic vascular resistance as well as pulmonary capillary wedge pressure. The hemodynamic benefits are associated with improvement in the signs and symptoms of congestive heart failure (CHF) as well as decreased mortality, regardless of the severity of CHF. In patients with asymptomatic LV dysfunction, therapy with ACE inhibitors prevented the development of CHF and reduced hospitalization and cardiovascular death. They also increase survival when administered early after an acute myocardial infarction (MI). Most recently, ACE inhibition was associated with improved clinical outcomes in a broad spectrum of high-risk patients with preserved LV function. The mechanism of ACE inhibitors benefits is multifactorial and includes prevention of progressive LV remodeling, prevention of sudden death and arrhythmogenicity and structural stability of the atherosclerotic process. Evidence suggests that ACE inhibitors are underutilized in patients with cardiovascular diseases. Efforts should be directed to prescribe ACE inhibitors to appropriate patients in target doses. It is reasonable to believe that ACE inhibitors have a class effect in the management of LV dysfunction with or without CHF and acute MI. Whether the same is true for ACE inhibitors in the prevention of ischemic events is not known yet.
This review summarizes physiology of circulating and local renin-angiotensin system (RAS), enzymatic properties and mechanism of action of angiotensin I converting enzyme inhibitors (ACEIs) on RAS, and implications of ACEIs in anesthetic management of patients treated with these drugs. ACEIs, through their effect on RAS, may improve cardiovascular functions, pulmonary dynamics, and body fluid homeostasis. Thus, ACEIs have become an integral part of management of patients with hypertension, congestive heart failure (CHF) and chronic renal disease. ACEIs, due to differences in their chemical structure, exert different pharmacological actions and can have protective or occasional damaging effects on different organs. The anesthesiologists are commonly involved in the management of patients treated with ACEIs. Thus, the role of ACEIs and their possible interaction with anesthetic agents must be an integral part of clinical decision-making during anesthesia Hemodynamic variation during anesthesia is mainly related to specific effects of anesthetic agents on sympathetic nervous system. Those with preoperative fasting, volume depletion and extended sympathetic blockade can have reduced vascular capacitance resulting in decreased venous return, reduced cardiac output and severe arterial hypotension. Angiotensin II (ANG2) a potent vasoconstrictor may counterbalance such hypotensive effect. During ACE inhibition ANG2 cannot counterbalance this hypotension. Thus, induction of anesthesia may cause severe hypotension in hypovolemic patients specifically in those receiving diuretics as a complement to ACEIs. Recent advances in RAS and the pharmacology of ACEIs have identified some predisposing factors and risks associated with anesthesia in patients treated with ACEIs. Practitioners should be vigilant, and readily have vasopressors, necessary fluids and other resuscitative measures for treatment of unexpected hemodynamic instability during anesthesia and surgery.
This study was designed to develop a method for quantitative assessment of infarct size in the conscious animal based on serial changes of serum creatine phosphokinase (CPK) activity. From 11 experiments in which myocardial CPK was injected intravenously in conscious dogs, the average CPK distribution space and average CPK fractional disappearance rate from serum were found to be 11.4% of body weight and 0.48% min respectively. In other experiments, myocardial infarction was produced in 22 conscious dogs by constriction of a left coronary artery snare and serum CPK activity was determined at frequent intervals for 24 hr. Since myocardial CPK depletion reflects infarct size, infarct size was determined directly by analysis of myocardial CPK content in the same animals 24 hr after coronary artery occlusion. CPK released from the infarct was determined from observed changes in serum CPK activity analyzed according to a model taking into account the fraction of CPK released from an infarct and the rates of appearance and disappearance of CPK activity from serum. Infarct size was calculated on the basis of observed changes in serum CPK and compared to infarct size determined directly by analysis of myocardial CPK depletion. Agreement was close and results from all experiments fit the equation: [infarct size (g) determined from serum CPK] = 1.13 x [infarct size (g) determined from myocardial CPK] - 1.3, r = 0.96, n = 22. The method described is useful for accurate assessment of infarct size in the conscious animal and for detection of modification of infarct size produced by pharmacologic interventions.
To determine whether plasma renin activity in addition to catecholamines could be used as risk indicators, these parameters were measured in 19 patients with acute myocardial infarction. During the course of hospitalization, five patients developed ventricular fibrillation and three, cardiogenic shock. On admission, heart rate, plasma norepinephrine, epinephrine, and renin levels of these eight patients were significantly higher than those of the other patients with uncomplicated course. Peak creatine kinase MB activity was positively related to initial plasma renin activity (r = 0.62, p less than 0.01). Thus, the patients with the highest sympathetic activity following an acute myocardial infarction also had the highest plasma renin levels. They seem particularly prone to develop large infarcts and life-threatening complications.
The anti-ischemic effect of midterm treatment with captopril (four weeks) was investigated in 12 hypertensive patients with coronary artery disease. All patients underwent exercise stress tests at the end of one week of treatment with hydrochlorothiazide and at the end of four weeks of treatment with captopril associated with hydrochlorothiazide. Captopril reduced the S-T depression measured at the same maximal rate/pressure product and the occurrence of effort-induced chest pain, but did not change systolic pressure, heart rate, maximal rate/pressure product, total workload sustained, or total working time. Captopril may be useful in the treatment of hypertensive patients with coronary artery disease.
This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.
In einer Doppelblindstudie wurde der Einfluß des β-Rezeptorenblockers Metoprolol auf die Infarktgröße und die während der Akutphase auftretenden Infarktschübe untersucht. Von 51 Patienten, die innerhalb der ersten 24 Stunden nach Beginn der akuten Symptomatik stationär aufgenommen wurden, erhielten 25 Metoprolol (initial 0,1 mg/kg Körpergewicht als Kurzinfusion, zwei Stunden später 100 mg per os, danach alle 12 Stunden die gleiche Dosis), 26 Placebo. Die Infusion begann in der β-Blockergruppe im Mittel 9 h 55 min ± 5 h nach Infarktbeginn (in der Placebogruppe 12 h ± 6 h 20 min). Als Kriterium der Infarktgröße dienten der Verlauf der Serumkurve des MB-Isoenzyms der Kreatinkinase (MBCK) sowie die mit 48 präkordialen Ableitungen ermittelten Q- und R-Zackenamplituden und ST-Streckenanhebungen. Mit Hilfe dieser Parameter wurde eine Infarktäusdehnung bei sieben Patienten der Placebogruppe und bei fünf der β-Blockergruppe gesehen. Ein positiver Trend zugunsten der Metoprololtherapie gegenüber der Placebogabe war im Hinblick auf die ST-Streckenanhebung, die Entwicklung von Q-Zacken, die Reduktion von R-Zacken und die Menge der ins Serum ausgeschwemmten MBCK nachweisbar. Bei Kombination der Q-Zackenausbildung und R-Zackenreduktion war das Signifikanzniveau mit P = 0,05 gerade erreicht. Außer einem Patienten mit einer initial relativen Sinusbradykardie tolerierten alle übrigen die β-Blockerbehandlung ohne Komplikationen. In jeder Gruppe starb in der postakuten Phase bis zum 14. Tag ein Patient plötzlich und unerwartet. Die Ergebnisse zeigen, daß eine β-Blockertherapie auch zu einem relativ späten Zeitpunkt nach Infarktbeginn noch einen günstigen Effekt auf die Infarktgröße und den Verlauf des Infarktes hat.
The role of sudden changes of arterial permeability to circulating macromolecules was investigated in relation to their possible role in the initiation of vascular disease.This study suggests that circulating platelets may play important roles not only in the initiation of mural thrombi, but in the maintenance of abnormal vascular permeability leading to overt vascular lesions. At the same time, it provides a working hypothesis for the study of the pathogenesis of accelerated vascular disease often found in some forms of arterial hypertension and/or intravascular thrombosis.
The ability of large doses of exogenous angiotensin II to cause widespread multifocal microscopic myocardial necrosis in the rabbit has been confirmed. Angiotensin II also consistently produced acute renal failure with, less consistently, renal tubular necrosis. Norepinephrine infusions caused histologically indistinguishable myocardial lesions, but did not detectably affect renal function or histology. Severe renal failure, induced by bilateral nephrectomy (with or without concurrent glycerol administration) was not associated with similar cardiac lesions. Acute renal failure of comparable or greater severity to that induced by angiotensin II was produced by intramuscular cephaloridine, and was not associated with cardiac lesions. Rabbits infused with saline intravenously or "sham"-operated by simply opening and closing the peritoneal cavity did not develop renal failure and showed no cardiac or renal lesions histologically. Myocardial lesions, apparently identical to those seen in the rabbits, were observed postmortem in three patients known to have had high circulating levels of angiotensin II before death, although in all three cases alternative explanations are possible. Unexplained arrhythmia, cardiac arrest, and central chest pain without clear cardiographic or serum enzyme evidence of myocardial infarction occurred in two other subjects with very high plasma levels of angiotensin II. These attacks ceased after bilateral nephrectomy and a consequent fall in plasma angiotensin II. The cardiac attacks in these five patients all occurred during or shortly after procedures, such as sodium-depleting dialysis, renal artery surgery, or diazoxide administration, known to cause increase in plasma concentrations of renin and angiotensin II.
Plasma catecholamine levels were determined in 26 cases of uncomplicated myocardial infarction within 24 hours of onset of acute chest pain. Blood samples were collected at time of entry and at 4-hour intervals during the 48 hours following admission. Average values of plasma catecholamines within 1 hour of onset of pain were 0.87 ng./ml +/- 0.21 and remained elevated during the first 24 hours period. A gradual fall in catecholamine values was observed during the second 24-hour period. Catecholamines were higher in patients with sinus tachycardia and lower in patients with sinus bradycardia, and were higher in patients with anterior or anterolateral infarction. Catecholamine values were significantly higher when determined while patients presented ventricular ectopic beats or ventricular tachycardia. Sinus tachycardia, ventricular arrhythmias, and elevated plasma catecholamine values may be considered indicators of pain, anxiety, and/or left ventricular dysfunction without necessarily being causally related between themselves.
The value of the electrocardiogram in assessing infarct size was studied using serial estimates of the MB isomer of creatine kinase (CK MB) in plasma, serial 35 lead praecordial maps in 28 patients with anterior myocardial infarction, and serial 12 lead electrocardiograms in 17 patients with inferior myocardial infarction. In patients with anterior infarcts, sigma ST, sigma R, sigma Q, sigma R/(Q+S), and the number of sites with ST elevation more than 2 mm or with QS waves, were obtained from each map. Correlation between both maximum sigma Q and maximum sigma ST with cumulative CK MB was highly significant. There was also a significant correlation between sigma R and sigma R/(Q+S) with cumulative CK MB. There was no significant correlation between maximum number of sites with ST elevation or with Q or QS waves and cumulative CK MB. Maximum sigma ST and number of sites with ST elevation predicted maximum sigma Q and number of sites with QS or Q waves at a time when infarction was not complete. In patients with inferior infarcts, there was a significant correlation between maximum sigma Q and maximum sigma ST in leads II, III, and a VF, and cumulative CK MB. This study shows that all the waves in the electrocardiogram are useful in assessing infarct size. The fact that maximum sigma ST predicts final sigma Q may be used to assess the efficacy of interventions designed to salvage ischaemic myocardium.
In 50 patients with proven acute myocardial infarction (AMI), left ventricular hemodynamics (pulmonary end-diastolic pressure [PAEDP]; cardiac index [CI]; stroke volume index [SVI]; and SVI/PAEDP were related to the size of the acute infarct. Acute infarct mass was calculated from serial determinations of serum creatine phosphokinase (CPK) every two hours, using a computer program. In 15 cases postmortem measurement of acute infarct size after staining with Nitro-BT was made and correlated with calculated infarct size. Correlation in this limited number of cases was good with a mean difference of 7 g. Acute infarct mass in 38 survivors was 46 +/- 5 g and was significantly smaller (P less than 0.05) than in the 12 nonsurvivors (76 +/- 12 g.) PAEDP in surviving patients was significantly lower (17 +/- 1 mm Hg) and SVI (36 ml/m2) and SVI/PAEDP (2.4 ml/m2/mm Hg) significantly higher than in the nonsurvivors (PAEDP: 24 mm Hg; SVI: 23 ml/m2; SVI/PAEDP: 0.86 ml/m2/mm Hg) (P less than 0.001 for all differences). Similar significant differences were observed between patients not in shock and those in cardiogenic shock. Although in 39 patients, in whom the infarction was their first, infarct mass was larger (58 +/- 6 g) than in 11 patients with repeat infarctions (37 +/- 8 g), left ventricular hemodynamics were slightly more impaired in reinfarctions (PAEDP: 21 +/- 3 mm Hg; CI:2.60 L/min/m2) than in first infarctions (PAEDP: 18 +/- 1 mm Hg; CI:2.82 L/min/m2). The occurrence of cardiogenic shock was a strong predictor of death; however, the wide scatter of the data for the parameters cardiac index, PAEDP, and acute acute infarct mass precluded their usefulness, when taken individually, in predicting survival. When a relationship between hemodynamics and infarct size was looked for, four constellations of individual patients were identified. These groups were defined by PAEDPs of above or below 18 mm Hg and infarct sizes above or below 65 g. Class A patients (N = 22) had a small infarct (29 +/- 4 g) and good pump function (PAEDP: 13 mm Hg; SVI: 40 ml/m2; SVI/PAEDP: 3.27 ml/m2/mm Hg); prognosis was good for these patients. In class B (N = 13) the infarct was large (96 +/- 8 g) and pump function markedly impaired (PAEDP: 26 mm Hg; SVI: 24 ml/m2; SVI/PAEDP: 0.98 ml/m2/mm Hg); 54% of these patients died. Five patients in class C had, in the presence of a large infarct (84 g), only a slightly elevated PAEDP of 17 mm Hg and an almost normal SVI of 37 ml/m2. In contrast, the ten class D patients had an infarct size (34 g) similar to that in class A, but high PAEDP (23 mm Hg) and moderately reduced SVI (31 ml/m2). In this group a high incidence of reinfarctions (six out of ten) occurred. It is concluded that infarct mass calculated from serial CPK analysis, as a single parameter, cannot be used to predict mortality or development of cardiogenic shock in an individual patient.
A modified method for the measurement of total creatine phosphokinase release from venous blood samples taken four-hourly after myocardial infarction has been used in 43 patients admitted to a Coronary Care Unit. The fractional decay rate (Kd) of enzyme activity has been measured by a standardized method in each patient, and accuracy of the calculation of total enzyme release has been improved by allowance for individual variations in decay rate, and discarding of data from which decay rates cannot be measured within confidence limits of less than plus or minus 15 per cent. Total enzyme release was greater in cases of transmural infarction than in patients with subendocardial infarction, and showed a good positive correlation with clinical indices of the extent of myocardial damage. As noted by previous workers, this method allows for the measurement of the rate as well as the extent of enzyme release, and so should prove useful in the clinical evaluation of therapeutic agents which might accelerate or retard the rate of myocardial necrosis in patients with acute myocardial infarction.
The existence of independently functioning local renin-angiotensin systems in a number of tissues has been firmly established by biochemical and functional evidence and, most recently, by the demonstration of genetic messages for components of the renin-angiotensin systems, such as renin and angiotensinogen, in several organs. In this review, local renin-angiotensin systems in the heart and vascular walls are described and the contribution of a local inhibition of converting enzymes to the cardiovascular actions of converting enzyme inhibitors is discussed. Most of the studies cited support the hypothesis that an inhibition of cardiac converting enzyme may be involved in the beneficial hemodynamic and metabolic actions of converting enzyme inhibitors in cardiovascular disease, such as hypertension and congestive heart failure, independent of the circulating renin-angiotensin system. Local effects on cardiac converting enzyme may contribute to the ability of converting enzyme inhibitors to reduce cardiac hypertrophy. Similarly, local converting enzyme inhibition in the vascular wall may not only constitute a mechanism involved in the antihypertensive effects of converting enzyme inhibitors, but may also contribute to the regression of hypertension-induced vascular hypertrophy. In addition to reduced local angiotensin II generation, converting enzyme inhibition may engender a potentiation of the local effects of kinins. This mechanism may be more important to the cardiovascular actions of converting enzyme inhibitors than initially thought.
We previously reported concentration-dependent protection of captopril against ischemia-reperfusion injury in the isolated rat heart. In order to study these effects in vivo, we developed a closed-chest pig model. Reversible occlusion of the left coronary artery was achieved with a PTCA catheter during one hour. Captopril (C) i.v. was given in two different concentrations (0.6 mg/kg/10 min + 0.3 mg/kg/2 hr and 6 mg/kg/10 min + 3.0 mg/kg/2 hr) during the experiments to 11 and 10 pigs, respectively, versus 12 controls, who received only saline. Due to malignant ventricular arrhythmias, nine pigs died during ischemia. At the end of the reperfusion period of two hours, eight pigs were alive in each group. In the C-treated pigs, maximum creatine kinase after two hours of reperfusion was significantly lowered to 6,337 +/- 709 U/L in the high dose group versus 8,285 +/- 851 U/L in the low dose group and 9,635 +/- 1,115 U/L in the saline group. A reduction of local inosine overflow in the coronary sinus was seen. Maximum noradrenaline overflow after 5 min reperfusion diminished dose-dependently to 695 +/- 284 and 3,129 +/- 1,728 pg/ml in the C treated groups versus 4,693 +/- 2,277 pg/ml in the saline group. Mean arterial blood pressure and cardiac output decreased significantly during ischemia and reperfusion, but no significant differences occurred between the treated and untreated groups. Reperfusion arrhythmias, mainly accelerated idioventricular rhythm disturbances, were comparable among the three groups. We conclude that in vivo administration of C reduces myocardial damage upon reperfusion after one hour of ischemia in a dose-dependent way.(ABSTRACT TRUNCATED AT 250 WORDS)
The protective effect of angiotensin-converting enzyme inhibitors (ACEI) on myocardial ischemia and reperfusion damage was estimated in rat hearts, both in vivo and in vitro. Enalapril 2.5 mg/kg ip pretreatment at 24 and 5 h before coronary occlusion, significantly blunted the rise of CPK (445 +/- 151 vs 649 +/- 244 mu/ml, P less than 0.05) and improved electrocardiogram (ECG) 8 h after coronary occlusion. In global ischemia and reperfusion ex vivo, enalapril improved contractility (0.9 +/- 0.2 vs 0.3 +/- 0.3 g, P less than 0.05) and coronary flow (15.6 +/- 3.3 vs 11.9 +/- 3.1 ml/min/g, P less than 0.05), shortened significantly the duration of reperfusion arrhythmia (3.1 +/- 2.7 vs 9.7 +/- 8.1 min, P less than 0.05). In Langendorffs heart, captopril remarkably preserved force of contraction (2.1 +/- 0.4 vs 1.4 +/- 0.4 g, P less than 0.01) and coronary flow (2.7 +/- 0.5 vs 3.6 +/- 0.9 ml/min/g, P less than 0.05) in segmental infarction deteriorated by angiotensin I. Captopril 10(-5) M infusion reduced the release of CPK (435 +/- 112 vs 640 +/- 123 mu/min coronary flow, P less than 0.05). This action was almost completely abolished by pretreating and infusing with indomethacin. As a positive control, prostacyclin 5 X 10(-7) M infusion further reduced the release of CPK to 330 +/- 77 mu/min. It is concluded that angiotensin-converting enzyme inhibitor can protect both myocardial ischemia and reperfusion damage in rat hearts. The mechanism of protection was ascribed to reduced production of angiotensin II by ACE inhibition and increased prostacyclin release in the myocardium.
To elucidate the role of bradykinin in the cardiac actions of angiotensin converting enzyme (ACE) inhibitors, experiments were performed in isolated ischaemic hearts from guinea pigs and rats treated with the ACE inhibitor ramipril and the bradykinin-antagonist D-Arg[Hyp2,Thi5,8,D-Phe7]BK. In guinea pig hearts bradykinin increased coronary flow. Single oral pretreatment with ramipril (10 mg/kg) potentiated but perfusion with the bradykinin antagonist abolished this effect. In ischaemic working rat heart preparations perfusion with ramiprilat (2.58 x 10(-7) mol/l) or single oral pretreatment with ramipril (1 mg/kg) protected the heart from the ventricular fibrillations that invariably occurred upon reperfusion after ischaemia. Lactate dehydrogenase and creatine kinase activities, as well as lactate formation, were decreased in the venous effluent of pretreated hearts. Moreover, ACE inhibition in the heart improved cardiodynamic and metabolic parameters; left ventricular pressure, (dp/dt)max and coronary flow were increased and myocardial tissue levels of glycogen, ATP and creatine phosphate were elevated. A comparable array of changes was seen when rat hearts were perfused with bradykinin (1 x 10(-10) mol/l), which reduced enzymatic activities in the perfusate and improved the metabolic parameters in the myocardium. These cardioprotective effects produced by both the ACE inhibitor ramipril and bradykinin were completely abolished when the bradykinin-antagonist (1 x 10(-5) mol/l) was added to the perfusate. They were only partially attenuated when indomethacin (1 x 10(-6) mol/l) was perfused. Higher concentrations of bradykinin (1 x 10(-7) mol/l) or ramiprilat (2.58 x 10(-5) mol/l) overcame the actions of the bradykinin-antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
The angiotensin-converting enzyme inhibitors, captopril, enalapril and perindopril, exert antiarrhythmic effects on early post-infarction arrhythmias in anaesthetized rats. These studies support the hypothesis that converting enzyme inhibitors could have a "cardioprotective" effect, but the doses used are probably "high" in relation to those therapeutically applicable to man.
Enalaprilic acid (MK-422), the biologically active diacid of the converting enzyme inhibitor enalapril, was studied in myocardial ischemia (MI). Acute left coronary artery ligation was produced in 62 male Sprague-Dawley rats, and infarct size was determined by left ventricular free wall (LVFW) creatine kinase (CK) activity. Administration of enalaprilic acid (2 mg/kg) 2 minutes and 24 hours after MI significantly blunted the reduction in LVFW CK activity at 48 hours after ligation, when compared to the MI rats given vehicle (6.4 +/- 0.5 vs 4.7 +/- 0.2 IU/mg protein, respectively; p less than 0.01). The percentage of LVFW spared was significantly (p less than 0.01) increased from 28 +/- 2% to 45 +/- 5% by MK-422. MK-422 also significantly blunted the loss of LVFW CK activity 48 hours after a coronary ligation (10 minutes) followed by reperfusion, when compared to vehicle (10.1 +/- 0.6 vs 8.3 +/- 0.6 IU/mg protein, respectively; p less than 0.05). This represents a significant increase in the percentage of LVFW spared, 65 +/- 5% vs 85 +/- 6% (p less than 0.05). These data indicate a significant protective action afforded by MK-422 in two different protocols of ischemic damage to the myocardium and suggest a role for the renin-angiotensin system in the extension of ischemic damage.
The effect of captopril on inducible sustained ventricular tachycardia (VT) one week after myocardial infarction was studied in 6 Yorkshire swine. In 24 pigs, controlled myocardial infarction (MI) was produced by reversible occlusion of the left anterior descending artery during 60 minutes using an inflatable balloon catheter. Four animals died during this procedure and another 4 during the first week. After 7 days, programmed electrical stimulation (PES) was performed in the surviving animals. Seven animals showed inducible VT, which could not be terminated in one. Subsequently, intravenous captopril (0.6-1.2 mg/kg) was administered as a rapid bolus injection. PES was repeated after 5 minutes and VT was no longer inducible in all 6 pigs (P less than 0.05). Right ventricular refractoriness decreased from 253 to 228 ms (n.s.). Blood pressure and heart rate were not significantly changed. We conclude that captopril can protect the heart against PES-induced VT late after MI. It is suggested that inhibition of angiotensin II and subsequent inhibition of noradrenaline may be responsible for this effect.
Many vasodilators have been tried as antianginal agents, but the reflex increase in sympathetic tone produced by these drugs necessitate their use with caution in patients with angina. In the first part of this study, captopril was given to 14 patients with angina and systolic arterial pressures of greater than 120 mm Hg. Over the short term, captopril decreased arterial blood pressure (from 110 +/- 18 to 98 +/- 18 mm Hg, p less than .01) without increasing heart rate (75 +/- 15 vs 74 +/- 15 beats/min), arterial concentrations of epinephrine (0.38 +/- 0.28 vs 0.34 +/- 0.25 nM) or norepinephrine (2.7 +/- 2.1 vs 2.8 +/- 2.1 nM), or transmyocardial norepinephrine balance (216 +/- 254 vs 146 +/- 170 p mol/min). Captopril decreased average myocardial oxygen consumption (9.7 +/- 4.1 to 8.2 +/- 2.7 ml/min, p less than .01). Given over the long term (mean 5.5 months), captopril decreased the severity of angina from NYHA classification 3.0 +/- 0.8 to 1.6 +/- 0.8. In the second part of this study, captopril was given in a prospective, randomized, double-blind, placebo-controlled study to 21 patients with stable exercise-induced angina and systolic arterial pressures greater than 120 mm Hg. Captopril increased exercise time (309 +/- 137 vs 374 +/- 142 sec, p less than .05) without changing anginal threshold (rate-pressure product 17.0 +/- 6.0 vs 17.1 +/- 5.6 X 10(-3)). We conclude that captopril decreases mean arterial pressure without causing a reflex increase in myocardial sympathetic tone.(ABSTRACT TRUNCATED AT 250 WORDS)
The antihypertensive and anti-ischaemic effects of methyldopa and captopril were compared in 12 hypertensive patients with coronary artery disease. The antihypertensive effect of alpha-methyldopa (A) and captopril (C) were significant and similar. On the other hand, while methyldopa did not increase the product of systolic pressure and heart rate and did decrease the effort-induced S-T segment depression, C increased the double product (DP) and decreased the ischaemic S-T changes. Captopril might be useful in the treatment of hypertensive patients with coronary artery disease.
Levels of serum cortisol, plasma free fatty acids (FFA), and urinary catecholamines were collected in 31 patients with acute myocardial infarction on the day of admission to the coronary care unit (samples obtained from 15 patients with diseases other than myocardial infarction were considered as controls). These values were correlated with the presence or subsequent development of left ventricular failure, arrhythmias, shock, or death. Sixteen of 17 infarction patients without the above complications had cortisol levels less than 20 µg%; 10 of 12 patients with complications had higher cortisol levels. All of the infarction patients without complications had plasma FFA levels less than 1100 µEq/liter, while six of nine patients with complications had levels of 1100 µEq/liter or higher. Fourteen of 16 patients without complications had urinary catecholamines less than 12.5 µg%, while seven of 10 patients with complications had levels greater than this. Of interest were a few patients without complications on admission, but with elevated cortisol or FFA levels, who developed complications on the following day. The results of the present study suggest that the generalized metabolic stress of acute myocardial infarction results in elevations of cortisol, FFA, and catecholamines as measurable biochemical indicators and/or predictors of the severity of the infarction.
Captopril, the first orally effective converting enzyme inhibitor, was administered to 14 patients with chronic heart failure for 6 week periods, in a double-blind crossover comparison with placebo. Captopril improved symptoms and exercise performance, while left ventricular internal dimensions were reduced. The fall in blood pressure induced by captopril was well tolerated. Glomerular filtration rate was reduced and effective renal plasma flow increased on captopril. No decline in body weight or total body sodium was seen, suggesting that a natriuresis had not occurred. Serum and total body potassium rose. Ventricular arrhythmias declined.
Acute left anterior descending coronary artery occlusion was produced in 21 conscious, chronically instrumented dogs. Forty minutes after coronary occlusion, nine dogs were given i.v. teprotide, 25 micrograms/kg/min, followed by oral doses of captopril, 10 mg/kg every 8 hours for 24 hours. The remaining 12 dogs served as saline-infused controls. In all dogs, acute coronary occlusion increased plasma renin activity and peripheral vascular resistance and reduced cardiac output, but did not change mean aortic blood pressure significantly. Teprotide significantly (p less than 0.05) decreased peripheral vascular resistance (from 3804 +/- 1158 to 2876 +/- 816 dy-sec-cm-5) (+/- SD) and mean aortic pressure (from 117 +/- 12 to 107 +/- 15 mm Hg), and increased cardiac output (from 2.63 +/- 0.67 to 3.12 +/- 0.74 l/min). Teprotide also produced a relative increase in flow to the renal and splanchnic circulations compared with the saline-treated controls. There were, however, no differences in segmental systolic shortening, blood flow in the normal or ischemic myocardium, or infarct size. These results indicate that the renin-angiotensin system may play an important role in dogs with acute coronary occlusion and that blockade of this system lowers systemic blood pressure and improves cardiac output. However, direct effects of renin-angiotensin system blockade on the myocardium are lacking; there were no changes in myocardial blood flow, myocardial mechanics or infarct size.
Enalapril, a new potent orally active angiotensin-converting enzyme inhibitor, was studied in cats subjected to acute myocardial ischemia. Enalapril, administered intravenously (2 mg/kg, plus 2 mg/kg/h) 30 min after ligation of the left coronary artery, significantly reduced the pressure-rate index, an indicator of myocardial oxygen demand. This was confirmed in isolated cat papillary muscles where enalapril reduced contractile force by 5-10%. During myocardial ischemia, enalapril reversed the elevated S-T segment of the electrocardiogram toward normal 2 h after the onset of ischemia. Moreover, enalapril significantly blunted the increases in circulating creatine kinase (CK) activity, as well as significantly prevented the loss in myocardial CK activity. These changes correlated with reduced myocardial loss of compounds containing free amino-nitrogen. Enalapril effectively acted as a converting enzyme inhibitor over the 5-hour course of the observation period. However, enalapril also acted as an angiotensin antagonist in isolated coronary arteries, a finding that may help explain its efficacy in myocardial ischemia. Enalapril did not appear to stabilize the membranes of cat liver lysosomes, and thus probably does not protect the ischemic myocardium by lysosomal stabilization.
The effects of angiotensin-converting enzyme inhibitor (CEI) SQ14225 on infarct size and regional myocardial blood flow were studied in 21 anesthetized dogs subjected to 6 hours of coronary occlusion. An area of myocardium at risk of necrosis was determined in vivo after 15 minutes of coronary occlusion but before CEI treatment (AR1) using an autoradiographic technique and after treatment after 6 hours of coronary occlusion (AR2) using a fluorescent dye technique. An in vitro area at risk (AR3), which measures coronary bed size, was determined by injecting Monastral dye postmortem. Infarct size was determined by planimetry of unstained myocardium after incubating heart slices in triphenyltetrazolium chloride. Regional myocardial blood flow (RMBF) was measured by injecting tracer microspheres simultaneously with measurements of AR1 and AR2. In 11 saline-treated control dogs (group A), infarct size averaged 93 ± 8% of AR1, 96 ± 2% of AR2 and 75 ± 6% of AR3, respectively. In 10 dogs treated with CEI (0.25 mg/kg/hour) between 30 minutes and 6 hours after coronary occlusion (group B), infarct size was smaller and averaged 68 AR3 (p < 0.05). RMBF in the ischemic zone remained constant in group A but increased by 62 ± 26% in group B (p < 0.025). In group B, mean arterial pressure decreased from 115 ± 6 to 7 mm Hg (p < 0.025) between 30 minutes and 6 hours after coronary occlusion and left atrial pressure decreased from 9.0 ± 1.8 to 5.7 ± 0.8 mm Hg (p < 0.0025). These measurements did not change in group A. Thus, CEI is potent in reducing infarct size in the dog after coronary occlusion. It may act by increasing collateral flow to the ischemic zone and reducing afterload.
To determine whether the renin-angiotensin-aldosterone system is stimulated in myocardial infarction, plasma renin activity and serum aldosterone were measured by radioimmunoassay in 95 patients with acute infarction. Urinary catecholamines, and sodium and potassium levels in blood and urine were also determined. Plasma renin activity and aldosterone were insignificantly increased in mild myocardial infarction as compared to a reference group comprising patients with angina pectoris. In patients with a complicated course, however, they were greatly augmented.
A close correlation was found between urine catecholamines and plasma renin activity and between urine noradrenaline and aldosterone. Aldosterone values were highly correlated with the urine potassium/sodium ratio.
Enzymatic estimates of myocardial infarct size based on plasma levels of MB creatine kinase (MB-CK) were compared with anatomic infarct size in 49 human hearts obtained at autopsy. The patients studied had been enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study program within 18 hr of the onset of acute infarction and were treated at one of five participating hospitals. Infarct size was estimated from serial measurements of plasma MB-CK made at the core laboratory for CK analysis. Hearts obtained at autopsy were studied independently by the core pathology laboratory without knowledge of the MB-CK levels or clinical results. Data from the two laboratories were compared at the data coordinating center. Of 49 hearts, 12 were excluded either because anatomic infarct size could not be established or because the infarct occurring at the time of enrollment in the MILIS study could not be distinguished with certainty from other infarcts. Of the remaining 37 hearts, peak MB-CK level was available in 36, but samples sufficient for estimation of infarct size were available in only 25. The overall correlation coefficient (Spearman) was .87 for these 25 hearts, indicating that enzymatic estimates of infarct size correlate closely with anatomic measurements. The results indicate that CK estimates of myocardial infarct size represent a valid clinical end point for assessing myocardial infarct size, and the effect of therapy thereon, in groups of treated and control patients.
This study correlated the location and size of posterolateral myocardial infarcts (MIs) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral MIs and no confounding factors of ventricular hypertrophy or bundle branch block in their ECG. Left ventricular anatomic MI size ranged from 1 to 46%. No patient had a greater than or equal to 0.04-second Q wave in any electrocardiographic lead and only 55% had a 0.03-second Q wave. A 29-point, simplified QRS scoring system consisting of 37 weighted criteria was applied to the ECG. Points were scored by the ECG in 85% of the patients (range 1 to 8 points). MI was indicated by a wide variety of QRS criteria; 19 of the 37 criteria from 8 different electrocardiographic leads were met. The correlation coefficient between MI size measured anatomically and that estimated by the QRS score was 0.72. Each point represented approximately 4% MI of the left ventricular wall.
The effect of i.v. nitroglycerin administration on indexes of infarct size was examined in 31 patients with acute myocardial infarction. Serial creatine kinase (CK) and CK-MB isoenzyme determinations were used to calculate infarct size. Twenty-nine patients served as controls. Two subgroups of the study group were formed to evaluate differences between early and late intervention. In the first group (n = 22), continuous infusion of nitroglycerin over 48 hours was initiated within 8 hours (mean 4.5 hours) after the onset of symptoms. Peak CK activity for the nitroglycerin-treated patients (n = 9) in this subgroup was 544 U/1 vs 871 U/1 for the controls (n = 13) (p less than 0.05). The rate of CK release was reduced from 79 to 33 U/1.hr (58%), as was total CK and CK-MB release (p less than 0.02). Calculated infarct size was 69 gEq in the controls and 48 gEq in patients receiving nitroglycerin (CK-MB: 69 vs 43 gEq, p less than 0.05). In the late intervention subgroup, nitroglycerin therapy was begun more than 8 hours (mean 12.8 hours) after the onset of symptoms. Here, too, use of the agent was associated with lower peak CK and CK-MB levels as well as a reduction in calculated infarct size (p less than 0.05). Hemodynamic measurements, recorded every 4 hours, showed that nitroglycerin also reduced left ventricular filling pressure significantly and cardiac output increased. Blood pressure fell slightly, and systemic vascular resistance declined. The results indicate that i.v. nitroglycerin reduces CK and CK-MB release and thus calculated infarct size in both early and late intervention.
Nitroglycerin and nitrates have long been contraindi‐cated in the treatment of acute myocardial infarction because of the possibility of an undesirable decrease in arterial blood pressure and the induction of cardiogenic shock. Nowadays nitroglycerin seems to be indicated at least in subgroups of patients with acute myocardial infarction. Intravenous nitroglycerin reduce left ventricular filling pressure up to 40% within several minutes. The effect is most pronounced if filling pressure is elevated. There is no decrease in arterial pressure with low dosage nitroglycerin and a 10 % decrease with higher dosages. Cardiac output and stroke volume were found to increase following nitroglycerin application in patients with left ventricular failure. This may be due to the improved regional ventricular function in areas with decreased coronary flow. A slight, but significant decrease in cardiac output was found in patients not in failure. Nitroglycerin seems to be the drug of choice in acute pulmonary edema, because of its internal bloodletting effect. Following sublingual nitroglycerin, left ventricular filling pressure decreased within 3–5 minutes in conjunction with clinical improvement of the patient.
High blood pressure in such patients is largely reduced. — Nitroglycerin, therefore, seems to be applicable even in patients with acute and marked arterial hypertension.
Clinical improvement was evident in patients with dyspnea or pain following myocardial infarction. The need for morphine was reduced. Myocardial ischemia as assessed by electrocardiographic ST‐segment elevation improved following application of nitroglycerin. This effect is more pronounced in patients with left ventricular failure.
In a randomized prospective study, 31 patients received intravenous nitroglycerin at least for 2 days and were compared to 29 patients with no specific therapy. CK and CKMB infarct size was 30 % less than in the control group. Even with nitroglycerin administration 8 hours after the onset of symptoms, CK and CKMB activities were significantly reduced.
Preliminary results showed early mortality to be reduced in patients receiving nitroglycerin; The rate of reinfarction also was lower. The incidence of angina pectoris 1 1/2 years after the infarct, however, was higher in patients receiving nitroglycerin therapy initially. Following infarct size reduction more ischemic myocardium remains, possible indication for further therapy such as bypass surgery. The improvement in myocardial ischemia seems to be the reason for the reduction in ventricular ectopic beats during treatment. The need for lidocaine was markedly reduced. Even bradycardia seems to be improved, since the use for atropine was only half that for the control patients. These results provide evidence that nitroglycerin and nitrates appear to be indicated in patients with acute myocardial infarction, especially in those with left ventricular failure.
This study evaluated by quantitative autopsy correlation a previously developed scoring system for estimating the size of myocardial infarcts based on the QRS complex of the electrocardiogram. This system was tested using electrocardiograms from patients with infarcts shown by autopsy to predominate in the inferior third of the left ventricle. The study was limited to patients whose electrocardiogram did not indicate left or right ventricular hypertrophy, left or right bundle branch block, or left anterior or posterior fascicular block. Thirty-one patients from 6 medical centers met these criteria. In the electrocardiogram of 28 of the 31 patients (90%), lead a VF exhibited a Q wave of at least 30 ms. The correlation coefficient between the total QRS score and the percent infarction of the left ventricle was 0.74. In patients without confounding factors in the electrocardiogram and with single infarcts, the electrocardiogram provides a marker for infarcts in the inferior third of the left ventricle and a quantitative QRS scoring system provides an estimate of infarct size.
This study was performed to determine the relationship between myocardial infarct size estimated by serum CK-MB methods and the extent of irreversible injury in acute myocardial infarction. In 321 consecutive patients, infarct size was estimated by different mathematical models, and in 22 patients who died in hospital, the extent of myocardial necrosis was determined by autopsy. We also investigated the depletion of CK-MB in infarcted tissue, the recovery of CK-MB in the plasma volume, and the estimation of CK-MB from plasma. Myocardial CK-MB depletion was relatively greater in the larger infarcts, whereas the recovery of enzyme in plasma was independent of the infarct size. Correction of serum CK-MB for changes in plasma volume improved the estimate significantly (p less than 0.05). The correlation between the measured infarct size (g) and the estimated infarct size (units per liter and gram-equivalents) was highly significant (r = 0.85--0.89, SEE = 23--27%, p less than 0.001). Thus, a semiquantitative expression of the extent of myocardial necrosis can be determined in vivo.
The ability of an independently developed QRS point score to estimate the size of infarcts predominantly within the anterior third of the left ventricular was evaluated by quantitative pathologic-electrocardiographic correlation. The study was limited to 21 patients with a single infarct documented by postmortem examination, for whom an appropriately timed standard 12 lead electrocardiogram was available that did not exhibit signs of left or right ventricular hypertrophy, left or right bundle branch block or anterior or posterior fascicular block. At necropsy the heart was cut into five to seven slices. The location and size of the infarct was quantitated by computer-assisted planimetry of the slices. The electrocardiogram of 19 (90 percent) of the patients exhibited either a Q wave or an R wave of no more than 20 ms in lead V2. The infarct in the two patients without this electrocardiographic finding was small, occupying 2 and 3 percent of the left ventricle, respectively. The percent infarction of the left ventricle correlated with the QRS point score (r=0.80). Thus in patients without complicating factors in the electrocardiogram and with a single infarct, the electrocardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarct size.
Clinical and experimental evidence suggest that sympathoadrenal activation contributes to mortality in patients with ischemic heart disease. To determine the level of sympathoadrenal activation in the very early phase of acute myocardial infarction (AMI) and to determine if location of infarction (anterior versus inferior) was related to sympathoadrenal activation, we studied norepinephrine (NE) and epinephrine (E) within 4 hours after the onset of symptoms and prior to any rise in plasma creatine kinase (CK). Mean (+/- SE) initial (NE = 591 +/- 111 pg/ml and E = 73 +/- 19 pg/ml), peak (NE = 1356 +/- 178 and E +/- 1098 +/- 608) and average (NE = 815 +/- 142 and E = 252 +/- 68) plasma catecholamine concentrations were considerably above normal (NE = 228 +/- 10 and E = 34 +/- 2 pg/ml, n 60) and values were similar for inferior and anterior infarctions. During an 18-month follow-up, three patients died in whom the AMI mean NE and E and peak CK were higher than in the eight late survivors. Thus the three AMI patients with peak EP values greater than 1000 died, whereas the eight AMI patients with peak EP values less than 1000 survived (p less than 0.01). The magnitude of sympathoadrenal activation early in the course of clinical AMI appeared related to the extent of myocardial damage and late mortality.
Angiotensin-and nore-pinephrine-induced myocardial lesions: Experimental and clinical studie\ in rabbits and man.Am HerirtJ89 Wesseling H: Concentration-dependent protection by captopril against myocardial damage during ischemia and reperfusion in a closed chest pig model
- Gavras H D Kreiner
- Brown
- Jj
- B Gray
- Lever Af
- W Macadani
- A Medina
- Jj Morton
- Robertson
Gavras H, Kreiner D, Brown JJ, Gray B, Lever AF, MacAdani W, Medina A, Morton JJ, Robertson JIS: Angiotensin-and nore-pinephrine-induced myocardial lesions: Experimental and clinical studie\ in rabbits and man.Am HerirtJ89,321-332 (1975) 5. deGraeff PA, van Gilst WH, Be1 K, de Langen CDJ, Kingma JH. Wesseling H: Concentration-dependent protection by captopril against myocardial damage during ischemia and reperfusion in a closed chest pig model. J Ccirdiovu.w Phcirincicd Y(suppl 2), S37-S42(1YX7)
Quantitative assessment ofthe extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity. .I Cliti Itnvst 50
- Shell We
- Jk
- Sobel
Shell WE, Kjekshus JK, Sobel BE: Quantitative assessment ofthe extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity..I Cliti Itnvst 50.26 14-2625 ( 197 I )
Converting enzyme inhibitors (captopril, enalapril, perindopril) prevent early postinfarction ventricular fib-rillation in the anaesthetized rat Lack of reflex increase in myocardial sympathetic tone after captopril: Potential antianginal effect. Circulation 7 I
- I Daly
- P B Mettauer
- Rouleau Jl D Cousineau
- Burgess
- Jh
Ribuot C, Rochette L: Converting enzyme inhibitors (captopril, enalapril, perindopril) prevent early postinfarction ventricular fib-rillation in the anaesthetized rat. Cctrdiorwsc Drug Ther 1, 5 1-55 (1987) I I. Daly P. Mettauer B, Rouleau JL, Cousineau D, Burgess JH: Lack of reflex increase in myocardial sympathetic tone after captopril: Potential antianginal effect. Circulation 7 I, 3 17-325 ( I 985)
Cardioprotective effects ofenalapril in acute myocardial ischemia Protective effects ofcaptopril and enalapril on myo-cardial ischemia and reperfusion damage of rat
- Lefer Am
- Rc Y Peck
- Li K Chen
Lefer AM, Peck RC: Cardioprotective effects ofenalapril in acute myocardial ischemia. Pharmucology 29,6 1-69 ( 1984) Y, Li K, Chen X: Protective effects ofcaptopril and enalapril on myo-cardial ischemia and reperfusion damage of rat. J Mol Cell Curdiol 19.909-9 15 ( 1987)
Value of electrocardiogram in predicting and estimating infarct size in man Selvester RH: Evaluation of a QRS scoring system for estiinating niyoc:irdial in-firct size. 11. Correlation with quantitative :inatomic findings for ;in-terior infarcts
- S Yusuf
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- Sleight
- Ldeker Re
- Gs Wagner
- Wk Ruth
- Alonso
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- Bishop
- Sp
- Bloor
- Cm
- Jt Fallon
- Cottlieb Gj
- Db
- Reirner Ka Phillips Hr
- Roark Sf
- Rogers Wj Rm Savage
- White
Yusuf S, Lopez, R, Maddison A, Maw P, Ray N, McMillan S, Sleight P: Value of electrocardiogram in predicting and estimating infarct size in man. Br Heart J42,286-293 (1979) p12),S147-S148(1985) 17. ldeker RE, Wagner GS. Ruth WK. Alonso DR, Bishop SP, Bloor CM, Fallon JT, Cottlieb GJ, Hackel DB, Phillips HR, Reirner KA, Roark SF, Rogers WJ, Savage RM, White RD. Selvester RH: Evaluation of a QRS scoring system for estiinating niyoc:irdial in-firct size. 11. Correlation with quantitative :inatomic findings for ;in-terior infarcts. Am J Crirdiol49. 1604-16 14 ( 1982)
Comparison of enzymatic and anatomic ehti-mates of myocardial infarct size in man Bussmann WD: Nitroglycerin in the treatment of acute myocardial infarction
- Db Hackel
- Ka Reimer
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- Roberts Ph R Stone
Hackel DB. Reimer KA, Ideker RE, Mikat EM, Hartwell TI), Parker CB. Braunwald EB, Buja M, Gold HK, Jaffe AS, Muller JE, Raabe DS, Rude RE, Sobel BE, Stone PH, Roberts R. and the MILIS Study Group: Comparison of enzymatic and anatomic ehti-mates of myocardial infarct size in man. Cirrulatiorr 70, 82483.5 ( 1984) 23. Bussmann WD: Nitroglycerin in the treatment of acute myocardial infarction. A r ~ a MrdSccitid651(suppl), 651, 165-373 (1981)
Wagner GS: Evaluation of a QRS scoring system for estimating myocardial in-farct s i x . IV. Correlation with quantitative anatoinic liiidings ii)r posterolateral infrlrcts
- Ward Rm White
- Rd Ldeker Re
- Hindinan
- Alonso Dr Nb
- Bishopsp
- Bloor
- Cm
- Jt Fallon
- Gottliebgj
- Hutchins Gm Db
- Reimer Ka Phillips Hr
- Roark Sf
- Rogers Wj Sp
- Wk Ruth
- Weiss Rm Jl Savage
- Selvester
Ward RM, White RD. ldeker RE, Hindinan NB, Alonso DR, BishopSP, Bloor CM, Fallon JT, GottliebGJ, Hackel DB, Hutchins GM, Phillips HR, Reimer KA, Roark SF, Rochlani SP, Rogers WJ. Ruth WK, Savage RM, Weiss JL, Selvester RH. Wagner GS: Evaluation of a QRS scoring system for estimating myocardial in-farct s i x. IV. Correlation with quantitative anatoinic liiidings ii)r posterolateral infrlrcts. Am J C~ircIiol53.7067 I 4 ( 1984)
Der Verlauf der Plasmakatecholamine Noradrenalin und Adrenalin bei akutem Myokardinfarkt: Beziehung zu Hämodynamik, Infarktgrösse und ventrikulärer Extrasystolie
- M Dresel
- W Falke
Concentration-dependent protection by captopril against myocardial damage during ischemia and reperfusion in a closed chest pig model
- Pa Degraeff
- Wh Van Gilst
- K Bel
- Cdj De Langen
- Jh Kingma
- H Wesseling
Angiotensin-and norepinephrine-induced myocardial lesions: Experimental and clinical studie\ in rabbits and man
- H Gavras
- D Kreiner
- J J Brown
- B Gray
- A F Lever
- W Macadani
- A Medina
- J J Morton
- Jis Robertson
Gavras H, Kreiner D, Brown JJ, Gray B, Lever AF, MacAdani W,
Medina A, Morton JJ, Robertson JIS: Angiotensin-and norepinephrine-induced myocardial lesions: Experimental and clinical
studie\ in rabbits and man.Am HerirtJ89,321-332 (1975)
Clinical measurement of myocardial infarct size. Modification of a method for the estimation of total creatine phosphokinase release after myocardial infarction. Cinuhtion 5 I
- R M Noms
- Rml Whitlock
- C Bamatt-Boyes
- C W Small
Noms RM, Whitlock RML, Bamatt-Boyes C, Small CW: Clinical
measurement of myocardial infarct size. Modification of a method
for the estimation of total creatine phosphokinase release after myocardial infarction. Cinuhtion 5 I, 614-620 (1975)
Selvester RH: Evaluation of a QRS scoring system for estiinating niyoc:irdial infirct size. 11. Correlation with quantitative :inatomic findings for ;interior infarcts
- Wagner Gs Re
- W K Ruth
- D R Alonso
- S P Bishop
- C M Bloor
- J T Fallon
- G J Cottlieb
- D B Hackel
- H R Phillips
- K A Reirner
- S F Roark
- W J Rogers
- R M Savage
- R D White
17. ldeker RE, Wagner GS. Ruth WK. Alonso DR, Bishop SP, Bloor
CM, Fallon JT, Cottlieb GJ, Hackel DB, Phillips HR, Reirner KA,
Roark SF, Rogers WJ, Savage RM, White RD. Selvester RH:
Evaluation of a QRS scoring system for estiinating niyoc:irdial infirct size. 11. Correlation with quantitative :inatomic findings for ;interior infarcts. Am J Crirdiol49. 1604-16 14 ( 1982)
Evaluation of a QRS scoring system for estimating myocardial infarct s i x . IV. Correlation with quantitative anatoinic liiidings ii)r posterolateral infrlrcts
- R M Ward
- R D White
- Ldeker Re
- N B Hindinan
- D R Alonso
- Bishopsp
- C M Bloor
- J T Fallon
- Gottliebgj
- D B Hackel
- G M Hutchins
- H R Phillips
- K A Reimer
- S F Roark
- S P Rochlani
- W J Rogers
- W K Ruth
- R M Savage
- J L Weiss
- R H Selvester
- G S Wagner
Ward RM, White RD. ldeker RE, Hindinan NB, Alonso DR,
BishopSP, Bloor CM, Fallon JT, GottliebGJ, Hackel DB, Hutchins
GM, Phillips HR, Reimer KA, Roark SF, Rochlani SP, Rogers WJ.
Ruth WK, Savage RM, Weiss JL, Selvester RH. Wagner GS:
Evaluation of a QRS scoring system for estimating myocardial infarct s i x. IV. Correlation with quantitative anatoinic liiidings ii)r
posterolateral infrlrcts. Am J C~ircIiol53.7067 I 4 ( 1984)
Kaltenhach M: Reduction of CK and CK-MB indexes of infarct size by intravenous nitroglycerin. Circulurion 63
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Btissinann WD, Passek D, Seidel W. Kaltenhach M: Reduction of
CK and CK-MB indexes of infarct size by intravenous nitroglycerin. Circulurion 63.61 5-622 ( I98 I )