The effects of SUN 1165, a novel sodium channel blocker, on ischemia-induced mitochondrial dysfunction and leakage of lysosomal enzymes in canine hearts.

The cardioprotective effect of SUN 1165, a novel sodium channel blocker, was investigated on ischemic myocardium. Nineteen anesthetized dogs were subjected to 2 hours coronary occlusion, and divided into 2 groups. In the control group, physiological saline was infused. In the SUN 1165 group, 2 mg/kg of SUN 1165 was injected intravenously. Two hours after occlusion, heart mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their functions (RCI and St.III O2) were measured polarographically with succinate as a substrate. Fractionation of myocardial tissue from both non-ischemic and ischemic areas was performed according to the method of Weglicki et al., and the activities of lysosomal enzymes (NAG and beta-gluc) were measured. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 hours occlusion were observed. Administration of SUN 1165 maintained mitochondrial function, and prevented the leakage of lysosomal enzymes caused by ischemia significantly. These results indicated that SUN 1165 has a cardioprotective effect in ischemic heart.