The increase of cellular
fatty acids appears to be one of the causes of the myocardial injury during
ischemia and reperfusion. This study was designed to examine whether a
hypolipidemic drug such as
clofibrate can reduce the myocardial injury during
ischemia and reperfusion.
Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional
ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global
ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The
clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by
creatine kinase release. Although the
clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the
free fatty acid levels of plasma and myocardium were much lower compared with control animals. The
clofibrate feeding was also associated with increased peroxisomal
catalase and beta-oxidation of
fatty acids. These results suggest that decreased levels of
free fatty acids in the plasma and the myocardium and increased
catalase activity induced by antilipolytic
therapy appear to provide beneficial effects to the myocardium during
ischemia and reperfusion.