EXTRACELLULAR-SUPEROXIDE DISMUTASE TRANSGENE OVEREXPRESSION PRESERVESPOSTISCHEMIC MYOCARDIAL-FUNCTION IN ISOLATED MURINE HEARTS

Background Myocardial injury after ischemia and reperfusion may be med iated, at least in part, by oxygen-derived free radicals; this supposi tion is supported by the observation that significant quantities of th ese radicals are generated during reperfusion. To directly assess the protective effect of extracellular superoxide dismutase (EC-SOD), this study was designed to investigate the ability of EC-SOD overexpressio n in the hearts of transgenic mice to protect myocardial tissue agains t ischemia-reperfusion injury by use of an isolated work-performing mu rine heart preparation and functional analysis. Methods and Results Te n transgenic mice (EC-SOD, 28 to 31 g) were studied and compared with 10 control mice (Ctl, 28 to 31 g) in terms of preischemic and postisch emic myocardial function. All hearts underwent cardiac harvest and arr est, followed by instrumentation and subsequent reperfusion with warm Krebs-Henseleit solution. Preload-dependent functional analysis was th en performed to evaluate cardiac output, contractility (dP/dt), heart rate, stroke work, and stroke volume before and after a 7-minute perio d of warm ischemia. Results are expressed as mean +/- SEM (ANOVA, pair ed/unpaired t tests). There was no significant difference in preischem ic myocardial performance for Ctl and EC-SOD mice. After warm ischemia , cardiac output in EC-SOD was significantly improved compared with Ct l (EC-SOD, 4.55 +/- 0.37 mL/min; Ctl, 2.55 +/- 0.28 mL/min; P<.05). Po st-ischemic dP/dt, stroke work, and stroke volume were also significan tly improved in EC-SOD compared with Ctl mice (EC-SOD, 1808 +/- 39 mm Hg/s, 745 +/- 67 dyne . cm, and 13.1 +/- 1.2 mu L, respectively; Ctl, 1497 +/- 87 mm Hg/s, 472 +/- 83 dyne . cm, and 8.2 +/- 1.5 mu L; P<.05 ). Conclusions EC-SOD overexpressed mice showed significant improvemen t in postischemic cardiac function compared with Ctl mice. Thus, EC-SO D overexpressed hearts are less susceptible to mild degrees of ischemi a-repel-fusion injury than normal hearts.