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Captopril, an ACE inhibitor, for optimizing reperfusion after acute myocardial infarction
The Annals of Thoracic Surgery, 1991
Captopril is an angiotensin-converting enzyme inhibitor that has been reported to be effective in salvaging postischemic reperfused myocardium by its ability to function as a free radical-scavenging agent. A study was performed in the isolated porcine-heart model evaluating the influence of pretreatment with captopril on salvage of myocardium after an induced myocardial infarction. Measurement was carried out of regional and global myocardial function, myocardial high-energy phosphate levels, creatine kinase release, malonaldehyde formation, and 6-keto-prostaglandin F,, generation. In an in vitro preparation, the influence of captopril for scavenging various free radicals was evaluated. A dose-response curve was carried out using this free radical-generating system and differing levels of captopril. Results of the study demonstrate that pretreatment with captopril at a or more than 20 years, details of the renin-angiotensin F system and the role it has in maintaining cardiovascular homeostasis have been known [l, 21. Recently, it has become evident that angiotensin can also be produced in the mammalian heart. The myocardium possesses angiotensin I1 binding sites, and angiotensin exerts a positive inotropic effect [3-51.
Effects of captopril on myocardial protection during cardioplegia
International Journal of Cardiology, 1993
The study aimed at checking effects exerted by captopril (C) on human myocardial ACE system as well as the role played by tissue ACE inhibition in reducing reperfusion damage. A human experimental model was used during cardioplegia due to aorto-coronary-by-pass (CABG). Fifty-four patients with coronary artery disease affecting 3 vessels having suffered from acute myocardial infarction anterior (AMI-ant), homogeneous as far as ejection fraction (35-55%). number of grafts (3), clamping time, age and sex, were randomised in a double blind experiment, and were given captopril or placebo (P). A total of 4 mg/I Captopril was mixed into the cardioplegic solution with blood according to the method of Buckberg (Buckberg GD. J Thorac Cardiovasc Surg 1987; 93: 127-139). Eight samples (blood/perfusate) were obtained from each patients and norepinephrine (NE). epinephrine (E) were assayed using an HPLC technique. Angiotensin 1 was assayed by RIA. CK was also assayed (units/ml). Bloodiperfusate samples were taken during CABG: (I) pre-pump; (2) pump sample; (3) pump preclamping; (4) coronary sinus; (5) coronary sinus sample during reperfusion; (6) coronary sinus during warm reperfusion; (7) after clamping sample; after decanulation; Results: Captopril group (29 patients): angiotensin I: () 399; pg/ml (P < 0.01). CK, captopril group: (I) 79; (2) 95; (3) 100; (4) 94; (5) 104; (6) 94; (7) 108; (8) 108; vs. placebo: (I) 76; (2) 120; (3) 135; (4) 152 (5) 225; (6) 272; (7) 247; (8) 228; units/ml. (P < 0.01).
Basic Research in Cardiology, 2010
Brief periods (a few seconds) of cyclic coronary occlusions applied early in reperfusion induce a cardioprotection against infarct size, called postconditioning (PostC) in which B 2-bradykinin receptors play a pivotal role. Since angiotensin-converting enzyme (ACE) inhibitors reduce degradation of kinins, we studied the effects of PostC on infarct size and postischemic myocardial dysfunction in both normotensive (WKY) and spontaneously hypertensive rats (SHR) acutely or chronically treated with the ACE inhibitor Captopril. Isolated hearts from SHR and WKY rats were subjected to the following protocols: (a) ischemia for 30-and 120-min reperfusion (I/R); (b) I/ R ? PostC protocol (5-cycles 10-s I/R); (c) pretreatment with Captopril for 4-weeks before to subject the hearts to I/ R with or without PostC maneuvers. Some SHR hearts were treated with Captopril during the 20-or 40-min early reperfusion with or without PostC maneuvers. Cardiac function was assessed in vivo with echocardiography. Left ventricular pressure and infarct size were measured ex vivo. Chronic Captopril significantly reduced left ventricular hypertrophy in SHR, and reduced infarct size in both WKY and SHR hearts. PostC maneuvers significantly reduced infarct size in WKY, but not in SHR hearts. Yet, PostC slightly improved postischemic systolic function in untreated SHR. Captopril given in reperfusion was unable to limit I/R injury in SHR hearts. Data show that PostC protection against infarct size is blunted in SHR and that PostC is unable to add its protective effect to those of chronic Captopril, which per se reduces cardiac hypertrophy and heart susceptibility to I/R insult.
Journal of Molecular and Cellular Cardiology, 1991
but not Immediate Captopril Therapy Improves Cardiac Function in Conscious Rats, Following Myocardial Infarction. foumal of A4olccular and Cellular Cardiology (1991) '23, 187-197. After myocardial infarction, the reninangiotensin system is found to be activated. While this response may be beneficial in acute failure, it could be detrimental in chronic stages. Therefore effects of captopril therapy were investigated during early and later phases after myocardial infarction in conscious rats, chronically instrumented for hemodynamic measurements. Hemodynamics were measured at baseline and after stimulating the heart by a volume load (cardiac function curve). Myocardial infarction decreased baseline cardiac output and impaired cardiac function, without effects on baseline mean arterial pressure, central venous pressure and heart rate. Captopril given 3 to 5 weeks after infarction improved cardiac function in a dose-dependent manner by increasing stroke volume, whereas stroke work was not affected. In contrast, captopril given from 1 to 21 days after infarction did not lead to improved cardiac function; instead, tachycardia together with a decreased stroke volume suggested deterioration, rather than improvement, of cardiac function. These data indicate that captopril therapy in chronically infarcted conscious rats improved cardiac function when treatment was started after completion of the healing process, but that early treatment not only failed to improve ventricular function, but may have a deleterious effect of the heart.
Clinical and Experimental Pharmacology and Physiology, 2009
1Recently, we demonstrated that oral captopril treatment improved diastolic function and attenuated cardiac remodelling after myocardial infarction (MI) in rats. Considering the feasible role of the brain renin–angiotensin system (RAS) in heart failure, in the present study we investigated the role of the captopril injected intracerebroventricularly (i.c.v.) on the progression of cardiac dysfunction.2Male Wistar rats underwent experimental MI or sham operation. Infarcted animals received daily i.c.v. injections of captopril (approximately 200 mg/kg; MI + Cap) or saline (MI) from 11 to 18 days after infarction. Electro- and echocardiogram assessments were performed before and after i.c.v. treatment (10 and 18 days after MI, respectively). Water and hypertonic saline ingestion were determined daily between 12 and 16 days after MI.3Electrocardiograms from the MI and MI + Cap groups showed signs that resembled large MI before and after i.c.v. treatment. However, despite similar systolic dysfunction observed in both groups, only captopril-treated rats exhibited reduced left ventricular (LV) dilatation and improved LV filling, as assessed by echocardiograms, and low levels of water ingestion compared with the saline-treated control group.4The results of the present study suggest that the brain RAS may participate in the development of cardiac dysfunction induced by ischaemia and that inhibition of the brain RAS may provide a new strategy for the prevention of diastolic dysfunction.Recently, we demonstrated that oral captopril treatment improved diastolic function and attenuated cardiac remodelling after myocardial infarction (MI) in rats. Considering the feasible role of the brain renin–angiotensin system (RAS) in heart failure, in the present study we investigated the role of the captopril injected intracerebroventricularly (i.c.v.) on the progression of cardiac dysfunction.Male Wistar rats underwent experimental MI or sham operation. Infarcted animals received daily i.c.v. injections of captopril (approximately 200 mg/kg; MI + Cap) or saline (MI) from 11 to 18 days after infarction. Electro- and echocardiogram assessments were performed before and after i.c.v. treatment (10 and 18 days after MI, respectively). Water and hypertonic saline ingestion were determined daily between 12 and 16 days after MI.Electrocardiograms from the MI and MI + Cap groups showed signs that resembled large MI before and after i.c.v. treatment. However, despite similar systolic dysfunction observed in both groups, only captopril-treated rats exhibited reduced left ventricular (LV) dilatation and improved LV filling, as assessed by echocardiograms, and low levels of water ingestion compared with the saline-treated control group.The results of the present study suggest that the brain RAS may participate in the development of cardiac dysfunction induced by ischaemia and that inhibition of the brain RAS may provide a new strategy for the prevention of diastolic dysfunction.
European Heart Journal, 1996
The antiarrhythmic effect of oral captopril was studied during the early (day 3) and late (day 14) phase of acute myocardial infarction among 304 patients in a randomized placebo-controlled substudy of ISIS^t. Ventricular arrhythmias (ventricular ectopic beats per hour) occurred significantly less frequently among captopril-allocated patients than among those allocated placebo at day 3 (logarithmic scale: 0-48 ± 0-8 captopril vs 0-84 ± 1-3 placebo; F<0O03) and at day 14 (0 51 ± 10 vs 0-77 ± 1-3; /><005). The number of patients with frequent ventricular arrhythmias (more than 10 ventricular ectopic beats per hour) was also significantly lower among those allocated captopril at day 3 (7-3% vs 14-4%; / > <0-05) and at day 14 (7-3% vs 14-8%; /><005). These results support the hypothesis that the activation of the renin-angiotensin-aldosterone and sympathetic system may underlie heart rhythm disturbances in acute myocardial infarction, and that early use of converting enzyme inhibitor therapy may ameliorate these disturbances.