Effect of gender and fatty acids on ischemic recovery of contractile and pump function in the rat heart

Abstract

Clinical studies have shown that the incidence of heart disease is lower in premenopausal women compared with men. However, women are at increased risk of developing cardiac dysfunction after myocardial infarction. During a myocardial infarction, plasma levels of free fatty acids increase and contribute to postischemic left ventricular dysfunction. The purpose of this study was to examine the effect of increasing concentrations of fatty acids on recovery of contractile parameters and pump function after 20 minutes of global ischemia and 30 minutes of reperfusion in male and female rat hearts. Hearts were isolated and perfused with 5.5 mM glucose and 50 muU/mL insulin alone or in the presence of 0.4 or 1.2 mM palmitate. To determine whether inhibition of fatty acid metabolism was accompanied by an improvement in recovery of cardiac function after ischemia, the inhibitor of mitochondrial palmitate uptake, oxfenicine (2 mM), was used in female hearts perfused with 1.2 mM palmitate. Twenty-two female and 21 age-matched male rats were used. In hearts perfused under normoxic conditions, 1.2 mM palmitate reduced cardiac output and systolic pressure in female rat hearts. Heart rate, ventricular contraction, and ventricular relaxation were similar between male and female hearts and were not altered by fatty acids. After transient ischemia, all contractile parameters in male hearts returned to preischemic levels, regardless of the level of fatty acids in the perfusate. Recovery of female hearts, however, was inhibited by fatty acids. Aortic flow, ventricular contraction, ventricular relaxation, and systolic pressure were significantly lower in female hearts compared with male hearts in the presence of 1.2 mM palmitate (P < 0.05). In female hearts perfused with oxfenicine, however, recovery of systolic pressure, cardiac output, and ventricular contraction was significantly increased compared with control hearts (P < 0.05). Our data indicate that the female myocardium is more sensitive to the effects of fatty acids after global ischemia compared with male hearts. This confirms that a gender effect exists in the recovery of heart function after ischemia, which can be accounted for by differences in ventricular contraction and relaxation.