Background: 

Polyunsaturated fatty acid-rich diets may decrease the risk of myocardial infarction and sudden cardiac death. These fatty acid derivatives can also activate different peroxisome proliferator-activated receptors (PPAR). The aim of our investigations was to study the effect of polyunsaturated fatty acid-rich diet and long-term pretreatment with fenofibrate, both started after the induction of myocardial infarction, on the development of heart failure in rats.

Methods: 

Myocardial infarction (MI) was induced in male Sprague-Dawley rats by ligation of the left main coronary artery during anesthesia. Two weeks later in the animals surviving the acute phase of MI, animals were randomly allocated to receive a diet supplemented with 10% pork fat (containing saturated fatty acids; SF) or 10% sunflower-seed oil (containing linoleic acids; SSO) for 10 weeks. Half of the animals in both dietary groups were pretreated by fenofibrate (F) (150 mg/kg/day for 3 weeks, then 75 mg//kg/day for 7 weeks, mixed to the dietary food). At the end of the feeding period during pentobarbitone anesthesia, the heart rate and arterial blood pressure changes were recorded, transthoracic echocardiography was performed (GE Vivid S5, 12 MHz probe) and dobutamine-stress was applied. As the completion of the experiments the myocardial infart size was determined after nitroblue-tetrazolium staining of heart slices.

Results: 

There were no significant differences in the baseline parameters of the heart rate and arterial blood pressure. The baseline stroke volume was higher in the fenofibrate pretreated dietary groups, compared to their corresponding controls (SF+F=270±28.3 vs. SF=219±26.0; SSO+F=219±21.8 vs. SSO=200±19.7 ml). The cardiac output significantly increased in the SF+F group, compared to the SF control (22.5±2.39 vs. 14.9±1.76 ml/min/100g; P<0.05). During dobutamine-stress the cardiac output increased in the SF group mainly due to the elevated heart rate. The cardiac output significantly improved in the SSO group (19.5±1.53 vs. 14.2±1.43 ml/min/100g; P<0.05), although there were no additional increases in the fenofibrate pretreated groups due to the increased baseline (SF+F=22.5±2.39 vs. 22±2.55; SSO+F=19.5±1.53 vs. 22.5±1.67 ml/min/100g).

Conclusion: 

According to our investigations long-term pretreatment with fenofibrate improved the effects of polyunsaturated fatty acid-rich diet in heart failure. As a result of fenofibrate treatment, the heart tolerated the sympathetic-stress without furter increase in cardiac output.

Supported by ETT 233/2009 and TÁMOP 4.2.1/B-09/1/KONV-2010-0005.