Abstract 100: Ranolazine Ameloriates Postresuscitation Hemodynamic Instability and Improves Survival with Good Neurological Recovery
Background. Deregulation of intracellular Ca2+ homeostasis plays a critical role in the pathophysiology of ischemia/reperfusion injury after cardiac arrest and CPR. We investigated effects of ranolazine on survival and functional recovery in a rat model of cardiac arrest and CPR. We hypothesized that ranolazine, by blocking slow Na+ current and consequently reducing post resuscitation intracellular Ca2+ overload, would reduce post resuscitation arrhythmia and improve survival.
Methods. Fourteen SD rats (530 ± 40 g) were randomized to receive intravenously ranolazine, 10 mg/kg (n=6), or vehicle (n=8). Fifteen mins later, ventricular fibrillation was induced and untreated for 8 min. CPR, including mechanical chest compression and ventilations, was then initiated and continued for additional 8 min prior to defibrillation. Arterial and right atrial pressures were monitored and coronary perfusion pressure (CPP) calculated. After return of spontaneous circulation (ROSC), episodes of arrhythmia were monitored, together with 72 hr survival and post ROSC neurological recovery.
Results. All the animals treated with ranolazine were successfully resuscitated and survived for 72 hr, while 6 of the 8 vehicle treated ones achieved ROSC and only 4 survived up to 72 hrs. Ranolazine treated rats presented a significantly shorter interval of post ROSC arrhythmia with hemodynamic instability compared to vehicle treated ones (p<0.02). Rats receiving ranolazine presented also greater mean arterial pressure and CPP compared to those that received vehicle (p<0.01). A full neurological recovery was observed in each animal treated with ranolazine, while a neurological impairment persisted in those treated with vehicle (p<0.015, Table).
Conclusions. Administration of ranolazine reduced post ROSC arrhythmia and hemodynamic instability. This led to a better post ROSC organ perfusion and ultimately accounted for a full neurological recovery, a benefit not reported so far.
- © 2012 by American Heart Association, Inc.