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15 July 2002

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

Nicole S. Wayman, Belinda L. Ellis, Christoph Thiemermann

Med Sci Monit 2002; 8(7): BR243-247 :: ID: 13612


Background: This study was designed to investigate the effects of two, chemically distinct activators of PPAR-α (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-α agonists clofibrate (0.3 mg/kg) caused a significant reduction in myocardial infarct size of 43%. Similarly, pre-treatment of rats with the PPAR-α 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-α reduce the tissue necrosis associated with acute myocardial infarction. We propose that fibrates and other PPAR-α agonists
may be useful in conditions associated with ischemia-reperfusion of the heart and other organs.

Keywords: Cardiotonic Agents - pharmacology, Clofibrate - pharmacology, Heart - drug effects, Hemodynamic Processes, Ligands, Myocardial Infarction - metabolism, Myocardium - metabolism, Myocardium - pathology, Peroxisome Proliferators - pharmacology, Pyrimidines - pharmacology, Rats, Wistar, Receptors, Cytoplasmic and Nuclear - agonists, Receptors, Cytoplasmic and Nuclear - metabolism, Transcription Factors - agonists, Transcription Factors - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750