Females Exhibit Relative Resistance to Depressive Effects of TNF on the Myocardium

Abstract

Background: Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in myocardial dysfunction following acute injury. It is unknown, however, if a gender-specific response to TNF infusion exists in isolated rat hearts. Elucidating such mechanisms is important to understanding the myocardial gender differences during acute injury. We hypothesize that females will exhibit a relative resistance to TNF-induced myocardial dysfunction compared to males and that menstrual cycle would influence the degree of female myocardial resistance to TNF-induced myocardial functional depression. Materials and methods: Adult male, proestrus female, and metestrus/diestrus female hearts were subjected to 60 min of TNF infusion at 10,000 pg/mL.min via Langendorff. Myocardial contractile function (left ventricular developed pressure, and the positive/negative first derivative of pressure) was continuously recorded. Results: 10,000 pg/mL.min of TNF markedly depressed myocardial function in males compared with other doses of TNF. Myocardial function was significantly decreased in males compared to females following TNF infusion. Additionally, both the proestrus and the metestrus/diestrus females exhibited equal resistance to TNF-induced myocardial dysfunction. Conclusion: Our study shows that females exhibit a significantly greater degree of resistance to TNF-induced myocardial depression. Moreover, data from this study suggest that fluctuations in estrogen during the reproductive cycle may have little to no influence on TNF-induced myocardial depression.