Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbi-mortality in obstructive sleep apnea (OSA) patients. Previous animal studies demonstrated that IH increases myocardial susceptibility to ischemia-reperfusion (IR). Among mechanisms involved in the pathophysiology of IR, modulation of endoplasmic reticulum (ER) stress seems to play a major role. Exercise is known to exert beneficial effects on the cardiovascular system and a growing body of evidence demonstrates a particular efficiency of high-intensity interval training (HIT). The aim of the present study was 1) to evaluate the effects of HIT on IH-induced increased susceptibility to IR; 2) to determine whether ER stress was involved.

Wistar male rats were exposed to 21 days of IH (21-5% FiO2, 60s cycle, 8h/day) or normoxia (N). After one week of IH alone, rats were daily submitted to both IH and HIT (2*24min, 15 to 30m/min). Rat hearts were either submitted to an IR protocol ex-vivo (30min-global ischemia followed by 120 min-reperfusion, Langendorff technic) or rapidly frozen to evaluate ER stress by Western Blot.

IH induced a significant increase in infarct size (35.4±3.2% vs 22.7±1.7% of ventricles, in IH and N respectively, p<0.05) that was corrected by HIT (28.8±3.9 vs 21.0±5.1% of ventricles, in IH and N respectively). This was accompanied by a myocardial ER stress IH-dependent, characterized by the increased expression of the ER stress sensor (i.e. GRP78) and the activation of the proapoptotic ER stress pathway (i.e. pPERK, ATF4 and CHOP). HIT conditioning prevented this IH-induced proapoptotic ER stress.

These findings show that HIT prevented the IH-dependent increased in myocardial susceptibility to IR, probably through a down-regulation of proapoptotic ER stress pathway. HIT could represent a good preventive strategy to limit myocardial ischemia reperfusion-related damages in OSA patients.