Ligands of the peroxisome proliferator-activated receptor-PPAR-a reduce myocardial infarct size.

Background: This study was designed to investigate the effects of two, chemically distinct activators of PPAR-a (clofibrate and WY14643) in a rat model of acute myocardial infarction.

Material/methods: Male Wistar rats were anesthetized with sodium thiopentone (120 mg/kg i.v.) and subjected to regional myocardial ischemia (for 25 min) and reperfusion (for 2 h). Area at risk was determined by injection of Evans Blue dye and infarct size after staining with nitroblue tetrazolium.

Results: Pre-treatment of rats with the PPAR-a agonists clofibrate (0.3 mg/kg) caused a significant reduction in myocardial infarct size of 43%. Similarly, pre-treatment of rats with the PPAR-a agonists WY14643 (1 mg/kg) caused a significant reduction in myocardial infarct size of 43%.

Conclusions: Taken together, these results show that ligands of PPAR-a reduce the tissue necrosis associated with acute myocardial infarction. We propose that fibrates and other PPAR-a agonists may be useful in conditions associated with ischemia-reperfusion of the heart and other organs.