Cariporide for Pharmacologic Defibrillation After Prolonged Cardiac Arrest

Background: We hypothesized that cariporide, a sodium-hydrogen exchange inhibitor, would be as cardioprotective during the global myocardial ischemia of prolonged cardiac arrest as it is in settings of coronary occlusion. Methods and Results: Fifteen Sprague-Dawley rats were randomized to receive bolus injections of cariporide or placebo in a dose of 3 mg.kg-1 into the right atrium either 5 minutes before, or at 8 minutes after, onset of ventricular fibrillation. Ventricular fibrillation was electrically induced and untreated for 8 minutes. Precordial compression, together with mechanical ventilation, was then started and continued for an interval of 8 minutes prior to attempted resuscitation. All but one placebo-treated animal were successfully resuscitated. Spontaneous defibrillation with restoration of circulation was observed in both cariporide-pretreatment and post-treatment groups but in none of the placebo-treated animals. Postresuscitation cardiac index, end-tidal CO2, mean aortic pressure, left ventricular systolic pressure, left ventricular end-diastolic pressure, and left ventricular contractile and lusitropic functions (dP/dt40, and -dP/dt) were significantly less impaired after cariporide, especially in the pretreated group, compared to electrically defibrillated controls. Postresuscitation ventricular premature beats were significantly reduced after cariporide. The duration of postresuscitation survival was significantly increased in animals pretreated with cariporide. Conclusions: Cariporide, when administered prior to and during cardiac arrest, improved both the success of resuscitation and postresuscitation myocardial function.