Sex and sex hormones determine myocardial infacrts size in a mouse model of sleep apnea

Introduction: Sleep apnea (SA) is associated with metabolic and cardiovascular diseases, such as diabetes and myocardial infarction (MI). Insulin resistance is a key metabolic alteration in diabetes that also aggravates MI. Intermittent hypoxia (IH - one of the main consequences of SA) induces insulin resistance and increases infarct size following myocardial ischemia-reperfusion (I/R) in rodents. However, while SA affects both sexes, most pre-clinical data have been obtained on males, limiting our understanding of sex-specific responses to IH and of the roles of sex hormones in males and females. Objective: We investigated whether sex and sex hormones determine myocardial infract size following IH and a potential association with insulin resistance. METHOD: C57Bl/6J mice underwent orchiectomy (ORX – males), ovariectomy (OVX – female) or sham surgery, followed by a 2-week recovery period. Mice were then exposed to 21 days of IH (21-5% O 2 , 60 episodes/hour, 8 hours/day) or normoxia (Nx). At the end of the IH or Nx exposures, after 6 hours of fasting, blood samples were collected (n=6 mice/groups) to measure insulinemia and glycemia and calculate the homeostatic model assessment of insulin resistance (HOMA-IR). Myocardial I/R injuries were induced on anesthetized mice (n=16/groups) by occlusion of the left coronary artery (45 minutes), followed by reperfusion (90 minutes) then injection of Evans blue. The hearts were dissected and later analyzed to determine the occluded and infarcted regions using colorimetric staining and planimetric measurement techniques. Results: In sham males, IH slightly (but not significantly) increases glucose and insulin levels, resulting in a significantly higher HOMA-IR, but these effects are not observed in ORX males. Additionally, while the occluded area is similar across groups, IH increases the infarcted area in sham males, but the opposite effect occurred in ORX males with a reduced infarcted area after IH vs Nx exposures. In sham females IH slightly reduces glucose levels, without altering insulin levels and the HOMA-IR, while it increases the infarcted area following myocardial I/R. In females maintained under normoxia, OVX slightly reduces glucose levels, but almost doubles insulin levels and the HOMA-IR, without altering the infarcted area following myocardial I/R. In OVX females, IH reduces insulin and HOMA-IR, but has no effect on the infarcted area. Conclusion: There is an apparent correlation between insulin resistance and the size of the infarcted area following IH only in males, thus the mechanisms underlying the elevated infarct size induced by IH could differ between males and females. Sex and sex hormones appear to be fundamental determinants of metabolic and cardiac responses to IH. Agir pour les maladies chroniques, Fédération Française de Cardiologie, CIHR. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.