The Effects of Short‐Term Versus Long‐Term Exercise on Reducing Infarct Size After Ischemia‐Reperfusion in Male and Female Rat Hearts

Abstract

Ischemic heart disease is the leading cause of death in both males and females worldwide, with myocardial infarction due to ischemia‐reperfusion (IR) injury being the most common manifestation. Exercise is known to protect the myocardium against IR injury, but the volume of exercise sufficient to confer cardioprotection is not well understood. A single bout of exercise has been shown to confer protection against IR injury, but it is not known whether longer term exercise training (weeks) adds additional cardioprotective benefit. In addition, it is unclear to what extent sex differences contribute to cardioprotection. To address these questions, we studied female and male Sprague‐Dawley rats (3 mo of age) randomly assigned to a 5 day exercise training (EX5d) group (n=20), an 8 week exercise training (EX8w) group (n=20), or a sedentary (Sed) control group (n=10). EX5d rats ran for 5 consecutive days, while EX8w animals ran 5 days a week for 8 weeks. The speed was gradually increased until animals were running 21–23 m/min for 60 min. Maximal running capacity improved in all groups as a result of training. EX5d animals improved maximal distance run by 31.9 ± 9% (pre vs post) while EX8w animals improved by 118.5 ± 15.6% (p<0.01, EX5d vs EX8w). At least 24 h after the last training session, animals were anesthetized and the left anterior descending coronary artery was occluded via suture to induce regional ischemia for 45 min, followed by 24 h of reperfusion. After 24 hours, occlusion was reestablished and 0.5% Evans blue dye was injected into the aorta and perfused through the heart. Hearts were then sectioned, placed in a 0.1% triphenyltetrazolium chloride solution and incubated at 37° C for 10 minutes, then flash frozen in OCT. Infarct areas were quantified using ImageJ software, and infarct values calculated as a percentage of the zone at risk (ZAR). Exercise training led to a significant reduction in infarct size, with Sed, 5d, and 8w animals having infarct sizes of 37.2 ± 3, 27.5 ± 2, and 21.4 ± 1% of the ZAR, respectively (p<0.01, Sed vs EX5d and Sed vs EX8w). Hearts from Sed females had significantly smaller infarcts than those of Sed males (41.8 ± 3 and 32.6 ± 1% of the ZAR, respectively). This sex difference persisted in response to exercise training, with females exhibiting smaller infarct sizes following 5 days of exercise training compared to males (25.1 ± 1 and 29.9 ± 1% of the ZAR, in females and males respectively (p<0.05)), as well as 8 weeks of training (19.4 ± 1 and 23.5 ± 1% of the ZAR, respectively (p<0.05)). When comparing within‐sex differences in cardioprotection, 8 weeks of exercise did not lead to significant infarct size reduction compared to 5 days of exercise in males (23.5 vs 29.9% of the ZAR). However, hearts from EX8w females had significantly smaller infarct sizes when compared to EX5d females (19.4 vs 25.1% of the ZAR, respectively; p<0.01). These results show that 1) long‐term exercise training can augment infarct sparing against IR injury when compared to short duration exercise, and 2) this effect is sex‐dependent.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.