Associations between female sex hormones, estrous cycle, ischemic preconditioning and myocardial infarct size after ischemia–reperfusion injury

Studies on sex differences in myocardial infarction (MI) typically focus on males versus females, the exploration of hormonal physiologic variations and their impact on the infarct size remains limited. The objective of this study was to examine whether infarct size after myocardial ischemia/reperfusion injury in female rats differs in different phases of the estrous cycle, and according to the levels of sex hormones; and to assess whether the effect of ischemic preconditioning on infarct size varies in different phases of the estrous cycle and between sexes. Female rats were divided into three groups based on the estrous cycle: proestrus, estrus, and diestrus. A fourth group consisted of ovariectomized female rats. Male rats were included as a fifth group, and orchiectomized males as a sixth group. Each group underwent ischemia/reperfusion injury, with or without prior ischemic preconditioning (IPC). Plasma sex hormone levels were measured with gas chromatography-tandem mass spectrometry. Females in the proestrus showed significantly smaller infarct size compared to all other groups. Multivariable analyses identified proestrus, IPC, and estradiol as independent predictors of smaller infarct size while male sex and gonadectomy as independent predictors of larger infarct size. There was a statistical interaction between IPC and both sex and hormonal status, with a greater protective effect of IPC on infarct size in males and gonadectomized rats. After ischemia-reperfusion, proestrus female rats developed the smallest while male and gonadectomized rats the largest infarct size. Conversely, IPC conferred greater cardioprotection in male and gonadectomized rats than females in proestrus.