The effects of cytochrome C on the extent of myocardial infarction and regional function of the ischemic myocardium.

The effects of cytochrome C, an electron carrier in the process of oxidative phosphorylation, on infarct size and regional left ventricular function after a coronary artery occlusion were investigated. Thus, in 30 dogs, 1 minute after left anterior descending coronary artery occlusion, 99mTc-labeled albumin microspheres (8 mCi) were injected into the left atrium for subsequent assessment of the hypoperfused zone, that is, the area at risk of infarction. Fifteen minutes after coronary artery occlusion, dogs were randomized into a control group (n = 15) and a cytochrome C-treated group (n = 15). The latter immediately received cytochrome C, 2.5 mg/kg intravenously. Six hours after coronary artery occlusion the dogs were sacrificed and their left ventricles were cut into 3 mm thick slices. Infarct size was determined by triphenyltetrazolium chloride staining and measured by planimetry. The same slices were then submitted to autoradiography and the hypoperfused zone was then measured by planimetry. The hypoperfused zone was 22 +/- 2% and 23 +/- 2% of the left ventricle in the control and treated groups, respectively (NS), indicating that the extent of myocardium at risk before treatment was similar. The extent of the hypoperfused zone which evolved to necrosis was 90 +/- 3% in the control group but only 50 +/- 7% in the treated group (p less than 0.001). Myocardial salvage in the treated group was paralleled by improvement in systolic wall thickness of the ischemic segment as measured by two-dimensional echocardiography. Thus, cytochrome C reduced the extent of myocardial necrosis by 44% and improved systolic function of the ischemic myocardium.