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Effects of early angiotensin-converting enzyme inhibition in a pig model of myocardial ischemia and reperfusion

van Wijngaarden, J., Tobe, T. J. M., Weersink, E. G. L., Bel, K. J., de Graeff, P. A., de Langen, C. D. J., van Gilst, W. H. & Wesseling, H., Mar-1992, In : Journal of Cardiovascular Pharmacology. 19, 3, p. 408-416 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

In a blind, randomized study, the effects of perindopril, a nonsulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, were compared with those of placebo in a closed-chest pig model of myocardial infraction. In anesthetized pigs, my ocardinal ischemia and reperfusion were induced by inflation and deflation of a catheter balloon in the left anterior descending coronary artery (LAD), respectively. Thirty minutes after induction of ischemia and 15 min before reperfusion, a bolus injection of 0.06 mg/kg perindoprilat (n = 12), the active compound of peridopril, or placebo (n = 12) was administered in the pulmonary artery of these animals. After the acute phase of myocardial infarction, treatment with 12 mg/day perindopril or placebo was continued orally for 2 weeks. During the entire treatment period, 7 of 12 animals died in the placebo group versus 2 of 12 animals in the perindopril group (Fisher's exact test p <0.04). This beneficial effect of perindopril on mortality could not be attributed to salvage of myocardial tissue because the increases in creatine phosphokinase and coronary venous purine levels were similar in perindopril- and placebo-treated animals. Neither were there any significant between-treatment differences in the hemodynamic and (neuro)humoral parameters during the acute phase of myocardial infarction. The difference in mortality was observed within 24 h after myocardial infarction. Prevention of acute pump failure and, especially, life-threatening ventricular arrhythmias may explain this improvement in survival by perindopril. Retrospectively, logistic regression analysis showed that, irrespective of treatment, survival was inversely correlated to plasma renin activity (PRA) before induction of ischemia (r = -0.33; p <0.02). High initial PRA levels most likely reflected increased angiotensin II (ANGII) activity, which might have been beneficially influenced by perindopril. In addition, during the acute phase of myocardial infarction, prostaglandin E2 (PGE2) levels were significantly higher in animals that survived than in animals that died, but to establish the role of these humoral parameters to morality in myocardial infarction definitively prospective studies are needed.

Original languageEnglish
Pages (from-to)408-416
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume19
Issue number3
Publication statusPublished - Mar-1992

    Keywords

  • ANGIOTENSIN-CONVERTING ENZYME INHIBITION, MYOCARDIAL ISCHEMIA, REPERFUSION, PIG, NEUROHUMORAL MODULATION, PERINDOPRIL, ACE-INHIBITORS, RAT-HEART, ARRHYTHMIAS, CAPTOPRIL, PROSTAGLANDINS, LEUKOTRIENES, INJURY

ID: 6308347