title: Pharmacologic defibrillation.
abstract: Ventricular fibrillation (VF) is generally sustained. The mechanism is, at least in part, caused by progressive accumulation of intracellular sodium and calcium ions during untreated ventricular fibrillation, which subsequently increases defibrillation threshold. Cariporide, a potent and specific inhibitor of the sodium-hydrogen exchanger, has been shown to reduce intracellular sodium and calcium concentration in the setting of myocardial ischemia and reperfusion. We hypothesized that cariporide would facilitate defibrillation from prolonged ventricular fibrillation in a rodent model of cardiac arrest and resuscitation. Fifteen Sprague-Dawley rats were randomized to receive bolus injections of cariporide or placebo in a dose of 3 mg/kg into the right atrium either 5 mins before or at 8 mins after onset of ventricular fibrillation. Ventricular fibrillation was electrically induced and untreated for 8 mins. Precordial compression together with mechanical ventilation was then started and continued for an interval of 8 mins before attempted electrical defibrillation. All but one placebo-treated animal were successfully resuscitated. Spontaneous defibrillation with restoration of circulation was observed in both cariporide pretreatment and treatment groups but in none of the placebo-treated animals. The duration of postresuscitation survival was significantly increased in animals pretreated with cariporide. Therefore, sodium-hydrogen exchanger inhibitors may provide new options in settings of cardiopulmonary resuscitation to facilitate defibrillation.
authors.affiliation: Institute of Critical Care Medicine, Palm Springs, CA, USA.
authors.forename: Shue-ren
authors.initials: SR
authors.lastname: Wann
authors.forename: Max Harry
authors.initials: MH
authors.lastname: Weil
authors.forename: Shijie
authors.initials: S
authors.lastname: Sun
authors.forename: Wanchun
authors.initials: W
authors.lastname: Tang
authors.forename: Tommaso
authors.initials: T
authors.lastname: Pellis
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D004554:Electric Countershock; D006146:Guanidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000188:drug therapy*
chemical_list: D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide