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.


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.
The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London, UK.
Nicole S
NS
Wayman
Belinda L
BL
Ellis
Christoph
C
Thiemermann
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002994:Clofibrate / Q000494:pharmacology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D008024:Ligands; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism*
D002316:Cardiotonic Agents; D008024:Ligands; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C006253:pirinixic acid; D002994:Clofibrate