Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury.

Abstract

Oxygen-derived free radicals can produce myocardial cellular damage, which might contribute to the ischemia-reperfusion injury and to heart failure (HF). However, the effects of oxygen radicals on myocyte structure have not been examined in the failing heart. We examined the susceptibility of intact cardiac myocytes isolated from control (n=16) and rapid pacing (240 bpm, 4 wks)-induced HF (n=8) dog hearts to an exogenous hydroxyl radical (.OH), generated from H(2)O(2) and Fe(3+)-nitrilotriacetate. The production of (.OH) was monitored by electron spin resonance with 5,5'-dimethyl-1-pyroline-N-oxide (DMPO) as a spin trap. The magnitude of DMPO-OH signals was not attenuated in the presence of either control or HF myocytes. (.OH) induced a time-dependent decrease in myocyte length (i.e. hypercontracture). The time to the onset of hypercontracture and that to the submaximal hypercontracture after exposure was significantly shortened in HF. Activities of superoxide dismutase, catalase, and glutathione peroxidase was not decreased in HF. HF myocytes were more susceptible to oxidative stress-induced cellular injury, which was not due to decreased antioxidant defense, but to the intrinsic properties of cells.