Cariporide for pharmacologic defibrillation after prolonged cardiac arrest

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.

Fifteen Sprague-Dawley rats were randomized to receive bolus injections of cariporide or placebo in a dose of 3 mgxkg(-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 CO(2), mean aortic pressure, left ventricular systolic pressure, left ventricular end-diastolic pressure, and left ventricular contractile and lusitropic functions (dP/dt(40), 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 post-resuscitation survival was significantly increased in animals pretreated with cariporide.

Cariporide, when administered prior to and during cardiac arrest, improved both the success of resuscitation and postresuscitation myocardial function.