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

Objective: Oxygen-derived free radicals can produce myocardial cellular dam age, 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. Methods: We examined the susc eptibility of intact cardiac myocytes isolated from control (n=16) and rapi d pacing (240 bpm, 4 wks)-induced HF (n=8) dog hearts to an exogenous hydro xyl radical ((OH)-O-.), generated from H2O2 and Fe3+-nitrilotriacetate. The production of (OH)-O-. was monitored by electron spin resonance with 5,5'- dimethyl-1-pyroline-N-oxide (DMPO) as a spin trap. Results: The magnitude o f DMPO-OH signals was not attenuated in the presence of either control or H F myocytes. (OH)-O-. induced a time-dependent decrease in myocyte length (i .e. hypercontracture). The time to the onset of hypercontracture and that t o the submaximal hypercontracture after exposure was significantly shortene d in HF. Activities of superoxide dismutase, catalase, and glutathione pero xidase was not decreased in HF. Conclusions: BF myocytes were more suscepti ble to oxidative stress-induced cellular injury, which was not due to decre ased antioxidant defense, but to the intrinsic properties of cells. (C) 200 1 Elsevier Science B.V. All rights reserved.