Isoproterenol-Induced Myocardial Ischemic Injury in the Rabbit: Functional and Ultrastructural Alterations

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Abstract
The functional and ultrastructural changes observed during myocardial ischemic injury (Mil) in the rabbit are described. Mil was induced by repeated subcutaneous injections of increasing doses of isoproterenol (ISO; 0.5 mg/kg on day 1, to 15.5 mg/kg on day 15). Measurement of cardiovascular changes revealed a significant decrease in the mean arterial pressure and an increase in heart rate of the ISO-treated animals. ISO treatment also initiated a variety of atrial and ventricular arrhythmias, including ventricular fibrillation, as well as significant ST segment elevations and the appearance of Q waves. Electron-microscopic analysis of hearts from ISO-treated animals showed accumulation of lipid and depletion of glycogen. The myofibrils had poorly defined Z bands and appeared as a homogenous mass. The most marked effects of ISO treatment were on the mitochondria, which appeared swollen and fragmented. The mitochondrial cristae were also disrupted and fragmented. A few amorphous electron-dense bodies were observed in and around the mitochondria. The changes observed in this study are qualitatively similar to those observed in the rabbit following coronary artery ligation.