• Francesca Fumagalli, Ilaria Russo, Lidia Staszewsky, Yongqin Li, Teresa Letizia, Serge Masson, Deborah Novelli, Marcella Rocchetti, Mara Canovi, Pietro Veglianese, Marco Gobbi, Roberto Latini, Antonio Zaza, and Giuseppe Ristagno.
• IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
• Heart Rhythm. 2014 Sep 1;11(9):1641-7.

BackgroundDuring ischemia, enhancement of the "late Na+ current" (I(NaL)) contributes to intracellular Ca2+ overload. Dysregulation of intracellular Ca2+ homeostasis plays a critical role in the pathophysiology of cardiac arrest and cardiopulmonary resuscitation (CPR), leading to ventricular arrhythmias and left ventricle (LV) dysfunction.ObjectiveThe purpose of this study was to investigate the effects of the I(NaL) blocker ranolazine on outcome of CPR in a rat model. We hypothesized that ranolazine might reduce postresuscitation arrhythmias and improve survival and recovery.MethodsEighteen rats were assigned to receive intravenous ranolazine 10 mg/kg or vehicle. Ventricular fibrillation was induced and untreated for 8 minutes. CPR then was performed for 8 minutes. ECG and arterial and right atrial pressures were monitored up to 3 hours after CPR. After resuscitation, LV function was monitored by echocardiography, and 72-hour survival with neurologic recovery was evaluated. Plasma was obtained for biomarkers of heart and brain injury.ResultsAll animals in the ranolazine group were resuscitated and survived up to 72 hours, whereas 72% in the vehicle group were resuscitated but 54% survived. The period of postresuscitation arrhythmia with hemodynamic instability was shorter in the ranolazine group compared to vehicle group (P < .02). Seventy-two hours after resuscitation, LV systolic and diastolic functions were better in the ranolazine group compared to vehicle (P < .05). Full neurologic recovery was observed in all ranolazine animals, whereas neurologic impairment persisted in the vehicle group (P < .02).ConclusionIn this model, ranolazine pretreatment reduced postresuscitation electrical and hemodynamic instability and improved 72-hour postresuscitation LV function and survival with good neurologic recovery.Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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