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Isoproterenol-induced myocardial ischemic injury in the rabbit: functional and ultrastructural alterations.

The functional and ultrastructural changes observed during myocardial ischemic injury (MII) in the rabbit are described. MII 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 homogeneous 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.