The antioxidant N-acetylcysteine preserves myocardial function and diminishes oxidative stress after cardioplegic arrest.

OBJECTIVE Oxidative stress contributes to myocardial ischemia-reperfusion injury. We hypothesized that administration of the antioxidant N-acetylcysteine would have beneficial effects on myocardial function after cardiopulmonary bypass and cardioplegic arrest. METHODS Anesthetized dogs (n = 18) were instrumented with myocardial ultrasonic crystals and a left ventricular micromanometer. Systolic function was measured by preload recruitable stroke work. Myocardial tissue water was determined by microgravimetry. Treated animals received 100 mg.kg(-1) N-acetylcysteine 10 minutes before initiation of cardiopulmonary bypass followed by 20 mg.kg(-1).h(-1) continuous infusion until 1 hour after cardiopulmonary bypass. After baseline, cardiopulmonary bypass and 2-hour crystalloid cardioplegic arrest was initiated, then reperfusion/rewarming for 40 minutes and separation from cardiopulmonary bypass. Myocardial function parameters and myocardial tissue water were measured at 30, 60, and 120 minutes after cardiopulmonary bypass. Oxidative stress was measured by 8-isoprostane concentrations in the coronary sinus plasma. RESULTS Preload recruitable stroke work did not decrease from baseline in the N-acetylcysteine group and was significantly greater in N-acetylcysteine group compared with controls at 30 (104% +/- 9% vs 80% +/- 4%; P <.05) and 120 minutes (98% +/- 7% vs 79% +/- 4%; P <.05) after cardiopulmonary bypass. Concentrations of 8-isoprostane in the coronary sinus plasma of the control dogs were significantly higher 30 minutes after cardiopulmonary bypass compared with baseline but were unchanged in the N-acetylcysteine group. Myocardial edema resolution was significantly greater in the N-acetylcysteine group at 30 minutes after cardiopulmonary bypass compared with control (-2.5% +/- 0.7% vs -0.3% +/- 0.5% myocardial tissue water; P <.05). CONCLUSIONS Administration of the antioxidant N-acetylcysteine preserves systolic function and enhances myocardial edema resolution after cardiopulmonary bypass/cardioplegic arrest. Furthermore, oxidative stress was significantly reduced in the treated animals. Therefore, our findings support the hypothesis that oxidative stress is the main cause for myocardial dysfunction after ischemia-reperfusion.