Daily reoxygenation decreases myocardial injury and improves post-ischaemic recovery after chronic hypoxia

Abstract

Objective: In contrast to the clinical evidence, experimental studies showed that chronic hypoxia (CH) confers a certain degree of protection against ischaemia-reperfusion damage. We studied the effects of daily reoxygenation during CH (CHReox) on hearts exposed to ischaemia-reperfusion. We also separated the intrinsic effects on the myocardium of CH and CHReox from those related to circulatory and nervous factors.

Methods: Fifty-one Sprague-Dawley rats were maintained for 15 days under CH (10% O(2)) or CHReox (10% O(2)+1 h day(-1) exposure to air). Normoxic (N, 21% O(2)) rats were the control. The animals were randomly assigned to one of the three following protocols: (1) protocol A: hearts (n=7 per group) were subjected to 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 3-h reperfusion, with measurement of the injury by tetrazolium staining; (2) protocol B: the end-diastolic pressure (EDP) and left ventricular developed pressure x heart rate (LVDP x HR) were measured in Langendorff-perfused isolated hearts (n=5 per group) during 30-min global ischaemia and 45-min reperfusion; and (3) protocol C: hearts (n=5 per group) were frozen for the determination of levels of endothelial nitric oxide synthase (eNOS) by Western blotting.

Results: CHReox hearts displayed greater phosphorylation of the eNOS and enhanced plasma level of nitrates and nitrites in comparison to CH hearts (P<0.0001, Bonferroni's post-test). The infarct size was greater in CH than in N hearts (P<0.0001, Bonferroni's post-test) while it was reduced in CHReox in comparison to CH and N hearts (P<0.0001). At the end of reperfusion, EDP was higher in CH than CHReox and N hearts (P=0.01, Bonferroni's post-test) while LVDP x HR was higher in CHReox and N than in CH hearts (P=0.03, Bonferroni's post-test).

Conclusions: Exposure to CH results in impairment of myocardial tolerance to ischaemia-reperfusion, greater injury and reduced recovery of performance, in agreement with clinical evidence. Infarct size, diastolic contracture and myocardial performance have been reduced, respectively, by 63%, 64% and 151% with daily reoxygenation compared with chronic hypoxia by accelerating intrinsic adaptive changes.