Decreased susceptibility of contractile function to hypoxia/reoxygenation in chronic infarcted rat hearts

Cardiac hypertrophy is associated with modifications in Ca2+ transport processes, enzymes of energy metabolism and antioxidant capacity. It is unknown whether these changes occur in infarct-induced hypertrophy with regard to an altered susceptibility to ischemia/reperfusion injury. We examined changes in sarcoplasmic reticulum (SR) Ca2+ transport, creatine kinase (CK) system, and the antioxidant enzymes glutathionperoxidase (GSH-Px) and superoxide dismutase (SOD) in rats 6 weeks after infarction due to coronary ligation (MI). Phenotypic modifications v sham operation (SHAM) were related to the contractile response of hypertrophied papillary muscle to hypoxia/reoxygenation for 30 min each. Under aerobic conditions we observed in MI v SHAM: decreases in isometric contraction and relaxation rate, a reduced Vmax-equivalent of sarcomeric shortening, a faster twitch-to-twitch decay of post-rest potentiation (PRC) which correlated closely to the decrease in SR Ca2+ uptake (-25%), a decrease in CK activity (-20%), reduced CK-MI and CK-MM, increased CK-MB and CK-BB, and enhanced activities of SOD (40%) and GSH-Px (50%). During hypoxia, an initial increase in peak force (PF) was followed by a slower PF decline in MI v SHAM. Reoxygenation caused a recovery of PF to approximately 30% in both groups; rates of contraction and relaxation recovered better in MI. In SHAM but not MI, twitch-to-twitch decay of PRC was accelerated after reoxygenation v aerobic control. The results suggest that adaptive changes in SR Ca2+ handling, CK isoenzymes and antioxidant enzymes may contribute to higher resistance against reduced oxygen supply and reoxygenation in hypertrophy due to MI.