A lazaroid mitigates postresuscitation myocardial dysfunction

Objective: Lazaroids, a series of 21-aminosteroids, reduce free radical mediated injury after ischemia and reperfusion. We hypothesized that the lazaroid U-74389G would minimize postresuscitation myocardial dysfunction and thereby improve neurologically meaningful survival in a rodent model after resuscitation from 8 mins of ventricular fibrillation. Design: Randomized, controlled laboratory study. Setting: University-affiliated research institute. Subjects: Sprague-Dawley rats. Interventions: Ventricular fibrillation was electrically induced in ten anesthetized Sprague-Dawley rats. The lazaroid agent U-74389G in a dose of 1 mg(.)kg(-1) or its vehicle serving as a placebo was injected into the right atrium after 7 mins of untreated ventricular fibrillation. One minute after injection of the compound, precordial compression was begun together with mechanical ventilation and continued for 6 mins before attempted electrical defibrillation. Measurements and Main Results: All animals were successfully resuscitated. Postresuscitation cardiac index, left ventricular end-diastolic pressure, the rate of left ventricular pressure increase measured at a left ventricular pressure of 40 mm Hg, and the maximum rate of left ventricular pressure decline were significantly less impaired in lazaroid-treated animals. This contrasted with control animals, which had significantly greater myocardial impairment, greater neurologic deficit, and lesser duration of survival. Conclusions: The lazaroid compound U-74389G, administered during cardiac arrest, mitigated postresuscitation myocardial dysfunction and improved survival.