Depression in mechanical function following ischemia in the female rat heart: role of fatty acids and altered mitochondrial respiration.

Background: Clinical studies have shown that the incidence of myocardial infarction is lower in women compared to men. However, following a myocardial infarct, women are at increased risk of developing ventricular dysfunction.

Objective: High levels of free fatty acids, observed in the clinical setting of ischemia, impair recovery of mechanical function during reperfusion of ischemic hearts. This study was designed to determine whether hearts from female rats are more sensitive to ischemia than male hearts when supplied with relevant levels of fatty acids.

Methods: Hearts from male and female Sprague-Dawley rats were isolated and perfused in the working mode with 5.5 mM glucose and 50 microU/mL insulin alone or in the presence of 1.2 mM palmitate. Cardiac function, expressed as heart rate-pressure product (RPP), was measured under preischemic conditions and during reperfusion following a period of transient global ischemia.

Results: Following the ischemic insult, RPP of male hearts returned to preischemic levels regardless of the substrates used. RPP of female hearts perfused with glucose alone also recovered to preischemic function. However, in female hearts perfused with the fatty acid, recovery of RPP was significantly lower compared to the female hearts perfused with glucose alone. In these hearts, recovery during reperfusion was only approximately 60% of preischemic function.

Conclusion: Our results indicate that the sensitivity of the female myocardium to postischemic dysfunction is enhanced in the presence of fatty acids, suggesting that a gender effect on recovery of cardiac function following ischemia exists.