Responses of chronically hypoxic rat hearts to ischemia: KATP channel blockade does not abolish increased RV tolerance to ischemia

Abstract

Chronic hypoxia may precondition the myocardium and protect from ischemia-reperfusion damage. We therefore examined the recovery of left and right ventricular function after ischemia and reperfusion (15 min each) in isolated blood-perfused working hearts from normoxic (Norm) and hypoxic (Hypo; 14 days, 10.5% O2) adult rats. In addition, the mRNA expression of hypoxia-inducible factor (HIF)-1α and the protein expression of endothelial nitric oxide synthase (eNOS) were measured. Postischemic left ventricular function recovered to 66 ± 6% and 67 ± 5% of baseline in Norm and Hypo, respectively. In contrast, postischemic right ventricular function was 93 ± 2% of baseline in Hypo vs. 67 ± 3% in Norm ( P < 0.05). Improved postischemic right ventricular function in Hypo (93 ± 2% and 96 ± 2% of baseline) was observed with 95% O2 or 21% O2 in the perfusate, and it was not attenuated by glibenclamide (5 and 10 μmol/l) (86 ± 4% and 106 ± 6% recovery). HIF-1α mRNA and eNOS protein expression were increased in both left and right hypoxic ventricles. In conclusion, postischemic right, but not left, ventricular function was improved by preceding chronic hypoxia. ATP-sensitive K+ channels are not responsible for the increased right ventricular tolerance to ischemia after chronic hypoxia in adult rat hearts.