Hemodynamic effects of 3,4-diaminopyridine in a swine model of verapamil toxicity.

Abstract

3,4-Diaminopyridine (3,4-DAP) may reverse the hemodynamic effects of severe verapamil toxicity. A nonblinded acute animal preparation. Eighteen chloralose-anesthetized and instrumented swine were poisoned with verapamil at 10 mg/kg/hr for five minutes and then 5 mg/kg/hr until a systolic blood pressure of 55 mm Hg was achieved. Heart rate, lead II ECG, mean arterial pressure, left ventricular dP/dT max, and cardiac index were monitored. Nine control animals received 0.2 mL/kg/min infusion of normal saline, and nine treatment animals received similar volumes of 1 mg/kg/min 3,4-DAP until systolic blood pressure reached 100 mm Hg, an elapsed time of 30 minutes, or death. Verapamil toxicity was produced in all animals following an average dose of 1.38 +/- 0.44 mg/kg verapamil, and resulted in diminished mean arterial pressure, dP/dT max, cardiac index, and heart rate to average values of 47%, 32%, 46%, and 88% of baseline values, respectively. Transient atrioventricular dissociation was noted in only 22% of cases. 3,4-DAP treatment (with an average dose of 14 +/- 5.6 mg/kg) resulted in significant increases in mean arterial pressure, dP/dT max, cardiac index, and heart rate to 136%, 298%, 149%, and 158% of baseline values, respectively. Mortality was unchanged (22% in both groups). 3,4-DAP treatment was complicated by muscle twitching, tachycardia (rate of more than 180) and hypertension (diastolic blood pressure of more than 110 mm Hg) each in 44% of cases. Although 3,4-DAP reversed the hypotensive and negative inotropic effects of verapamil toxicity, it failed to improve survival and resulted in several complications including muscle twitching, tachycardia, and hypertension.