Isoproterenol-induced myocardial alterations in alloxan-diabetic rabbits

This study was undertaken to characterize catecholamine-induced myocardial necrosis in 10-week alloxan-diabetic rabbits. Myocardial injury was induced by administering graded doses of isoproterenol (ISO) for 15 days. Injection of ISO to control and diabetic rabbits resulted in atrial tachycardias and ventricular fibrillation. The severity of the arrhythmias and the overall mortality was the same in both groups of animals. Analyses of serum biochemical parameters revealed significant increases in blood glucose, free fatty acids and total cholesterol in the ISO-treated diabetic animals relative to ISO-treated controls. ISO-treatment of both control and diabetic animals showed similar increases in heart weight, left ventricular weight and myocardial total water content. Analyses of various subcellular organelle marker enzyme activities indicated a significant decrease in the K+, Ca2+-stimulated sarcoplasmic reticulum, mitochondrial (azide-sensitive) and sarcolemmal Na+, K+-stimulated ATPase activities, decreases in ATP and glycogen and increases in myocardial sodium content in both the ISO-treated control and diabetic animal hearts. In addition, significant accumulation of Ca2+ and hydroxyproline were evident in the ISO-treated diabetic animal hearts.