Ranolazine ameliorates postresuscitation electrical instability and myocardial dysfunction and improves survival with good neurologic recovery in a rat model of cardiac arrest

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, Giuseppe Ristagno

Research output: Contribution to journalArticle

Abstract

Background During ischemia, enhancement of the "late Na+ current" (INaL) 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. Objective The purpose of this study was to investigate the effects of the INaL blocker ranolazine on outcome of CPR in a rat model. We hypothesized that ranolazine might reduce postresuscitation arrhythmias and improve survival and recovery. Methods Eighteen 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. Results All 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

Original languageEnglish
Pages (from-to)1641-1647
Number of pages7
JournalHeart Rhythm
Volume11
Issue number9
DOIs
Publication statusPublished - 2014

Keywords

  • Cardiac arrest
  • Myocardial dysfunction
  • Neurologic recovery
  • Outcome
  • Postresuscitation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Ranolazine ameliorates postresuscitation electrical instability and myocardial dysfunction and improves survival with good neurologic recovery in a rat model of cardiac arrest'. Together they form a unique fingerprint.

  • Cite this