Aims: 

We investigated the influence of long-term pretreatment with fenofibrate, an activator of peroxisome proliferator-activated receptor-a (PPARa), on the effect of saturated (SF) or polyunsaturated fatty acid (PUFA) rich diet during myocardial ischemia-reperfusion in rats.

Methods: 

Male Sprague-Dawley rats were fed a diet enriched with 10% pork fat (containing SF) or 10% sunflower-seed oil (containing linoleic acid, as PUFA) for 4 weeks. Half of the animals were pretreated with fenofibrate (150 mg/kg/day orally) for 2 weeks before production of acute coronary artery occlusion for 40 min followed by 120 min reperfusion during pentobarbitone anesthesia. The incidence of arrhythmias, the ECG and the left ventricular pressure changes were registered during the experiments.

Results: 

PUFA diet significantly decreased the occurrence of ventricular arrhythmias (ventricular tachycardia, VT 61% vs. 89% in SF fed animals, P<0.05) and improved the survival rate during coronary artery occlusion (91% vs. 57%, P<0.05). Long-term fenofibrate pretreatment also decreased the occurrence of arrhythmias in SF fed animals (VT 59%) and improved survival (82%). Fenofibrate pretreatment in PUFA fed animals resulted in further decrease in the incidence of VT (50%). The PPARa activator pretreatment also decreased the myocardial infarct size in PUFA-rich diet fed animals after 40 min ischemia and 120 min reperfusion as determined by triphenyltetrazolium staining (12.3±1.9% vs. 18.4±1.9% in PUFA fed animals, P<0.05).

Conclusion: 

The present investigations suggest that long-term fenofibrate pretreatment significantly decreases the severity of myocardial ischemia-reperfusion injury in anesthetized rats. After feeding a PUFA-rich diet this PPARa receptor activator may offer further cardioprotective effect.

Support: 

ETT 233/2009, TÁMOP-4.2.2-08/1-2008-0013, TÁMOP-4.2.1/B-09/1/KONV-2010-0005