An Experimental Study on Drugs for Myocardial Infarction

Abstract

Myocardial infarction ranks high among the causes of death In adults and the establishment of its prophylactic measures and therapeutic means is one of the primary tasks assigned to today's medicine. In the pathogenesis of myocardial infarction, coronary atherosclerosis plays an important role. Many attempts have so far been made in order to prevent the progress of atherosclerosis, but none of them have led to a directly effective therapeutic means for myocardial infarction. Therefore, the improvement of oxygen supply has been tried through increasing endocardial blood supply. Once coronary sclerosis is established, however, blood flow is not expected to be improved beyond a limited extent. It may be advisable to take a different approach to prevent myocardial infarction by a mechanism of action other than coronary vasodilation. The author studied various models of experimental myocardial infarction, and selected the model described by Rona et al. (1959) because of its easy duplicability, simplicity in procedure and histopathological similarity to myocardial infarction in men. The present study was undertaken to investigate biochemical and histopathological changes induced by large multiple doses of isoproterenol in rats and to obtain information about effects of some drugs on these changes. Methods: 1. Male Wistar rats, weighing 190 to 250g, were used in this study. Cardiac necrosis enlargement were induced by dl-isoproterenol at a dose of 80mg/kg s.c. daily for two days, and examined at various stages. Time course changes in the development of myocardial necrosis were examined by biochemical and histopathological procedures. Effects of some drugs on myocardial necrosis were also investigated. 2. Biochemical determination Serum enzymes: Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were measured by the method of Reitman and Frankel, and creatine phosphokinase (CPK) by the Kuby's method. Serum lipids: Cholesterol and triglycerides were determined by the method of Technicon's autoanalyzer methodology N-24a and methodology N-70 respectively. Serum free fatty acids (FFA) were measured by the Novak's method (the animals unfasted). Hematocrit (Ht.): By high speed centrifugation.