The effect of carbon dioxide, lidoflazine and deferoxamine upon long term survival following cardiorespiratory arrest in rats

This study examined the effect of carbon dioxide, lidoflazine and deferoxamine therapy upon the 10-day survival incidence and subsequent neurologic function of rats subjected to 7 min of cardiorespiratory arrest with resuscitation. Cardiac arrest (asystole) was induced at time zero by injection of cold, 1% KCl into the left ventricle of ketamine-anesthetized rats pretreated with succinylcholine. Positive pressure ventilation was discontinued at time zero. Cardiopulmonary resuscitation (CPR) was begun at 7 min, and animals with return of spontaneous circulation were entered into the study. Twenty treated rats were ventilated for 1 h with 7% carbon dioxide-93% oxygen and given lidoflazine (2.0 mg/kg, i.v.) and deferoxamine (50 mg/kg, i.v.) 5 min after CPR. Twenty control rats were ventilated for 1 h with 100% oxygen and given lidoflazine vehicle and deferoxamine vehicle. Lidoflazine treatment (1.0 mg/ kg) for the treated group, or lidoflazine vehicle for the control group, was repeated at 8 h postresuscitation. At 2 days postresuscitation, 75% of treated rats vs. 25% of control rats were alive (CHI² = 10.0, d.f. = 1, P < 0.01), and at 10 days, 60% of treated rats vs. 25% of control rats were alive (CHI² = 5.01, d.f. = 1, P < 0.05). There was no detectable neurologic deficit among survivors in either group at 15 days. The combination of carbon dioxide, lidoflazine and deferoxamine, administered after return of spontaneous circulation, is a simple and easily administered treatment regimen that improves the survival incidence without neurologic deficits in this animal model of cardiorespiratory arrest and CPR.