Greater impairment of energy metabolism and coronary flow in type 2 diabetic female rats than in male during myocardial ischemia-reperfusion injury

Abstract

Type 2 diabetic women are at greater risk of cardiovascular (CV) diseases than men, but the mechanisms involved are still poorly understood. The objective of this study was to investigate the effect of sex on the myocardial tolerance to ischemia-reperfusion (IR) injury in type 2 diabetic Goto-Kakizaki (GK) rats. We performed ex vivo experiments on isolated perfused hearts to evaluate tolerance to IR injury of male and female GK and Wistar rats. We simultaneously measured energy metabolism by 31P magnetic resonance spectroscopy, myocardial function and coronary flow. At the end of the experiments, biochemical analyses were performed on plasma and hearts. GK rats had cardiac hypertrophy and higher glycemia than control rats, without effect of sex. Basal oxidative stress was significantly higher only in female GK rats in comparison to other groups, with higher plasmatic level of 8-iso-PGF2α. Male and female GK rats had impaired cardiac function before and after IR injury in comparison to respective controls. Interestingly, female GK rats had greater impairment of cardiac function than male GK during reperfusion, associated with decreased ATP and PCr level, and higher impairment of coronary flow. Biochemical analyses in hearts showed downward trend in SIRT1 expression in GK rats versus control groups, without sex-effect. Citrate synthase activity and SIRT3 protein expression were similar between groups. These results indicate that sex influences the myocardial tolerance to IR injury in type 2 diabetes. Mitochondrial and endothelial dysfunction might explain why female GK have lower myocardial function during reperfusion. These results may be related to the higher risk of cardiovascular complications among type 2 diabetic women.