Influence of Intrinsic Aerobic Exercise Capacity and Sex on Cardiac Injury Following Acute Myocardial Ischemia and Reperfusion

Purpose: Previous reports have suggested that intrinsic aerobic running capacity (Low = LCR, high = HCR) in otherwise sedentary animals may influence cardiovascular health. Relative to the HCR phenotype, the LCR phenotype is characterized by decreased endothelial reactivity, increased susceptibility to reperfusion-induced arrhythmias, and increased diet-induced insulin resistance. The LCR phenotype has been characterized as a “disease prone” model, with the HCRs as “disease resistant”. The extent or sex dependence of these effects in an overt infarction is not known. Methods: Regional myocardial IR was induced in vivo by either 15 or 30 minute ligation of the LAD, followed by two hours of reperfusion. Global ischemia was induced in isolated hearts ex vivo using a Langendorff perfusion system and cessation of perfusion for either 15 or 30 minutes followed by 2 hours of reperfusion. Infarct size was determined using 2, 3, 5 - triphenyltetrazolium chloride (TTC) staining, and normalized to area at risk in the regional model, or whole heart in the global model. Portions of the tissue were paraffin embedded for H&E staining and histology analysis. Results: Phenotype dependent differences in infarct size were seen with 15 minute occlusion/2 hour reperfusion (LCR > HCR, p LCR female, p HCR female, p < 0.05 regardless of length of occlusion, or ischemia model. Conclusions: There is cardioprotection afforded by high intrinsic aerobic capacity, but it is not infinite/continuous, and may be overcome with sufficient injury burden. Phenotypic selection based on endurance running capacity preserved sex differences in response to both short and longer term coronary occlusive challenges. Outcomes could not be associated with differences in system characteristics such as circulating inflammatory mediators or autonomic nervous system influences, as similar phenotypic injury patterns were seen in vivo, and in isolated crystalloid perfused heart ex vivo.