HEMODYNAMIC-EFFECTS OF 3,4-DIAMINOPYRIDINE IN A SWINE MODEL OF VERAPAMIL TOXICITY

Study hypothesis: 3,4-Diaminopyridine (3,4-DAP) may reverse the hemody namic effects of severe verapamil toxicity. Design: A nonblinded acute animal preparation. Interventions: Eighteen chloralose-anesthetized a nd 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 con trol animals received 0.2 Ml/kg/min infusion of normal saline, and nin e treatment animals received similar volumes of 1 mg/kg/min 3,4-DAP un til systolic blood pressure reached 100 mm Hg, an elapsed time of 30 m inutes, or death. Results: Verapamil toxicity was produced in all anim als following an average dose of 1.38 +/- 0.44 mg/kg verapamil, and re sulted in diminished mean arterial pressure, Dp/Dt max, cardiac index, and heart rate to average values of 47%, 32%, 46%, and 88% of baselin e values, respectively. Transient atrioventricular dissociation was no ted in only 22% of cases. 3,4-DAP treatment (with an average dose of 1 4 +/- 5.6 mg/kg) resulted in significant increases in mean arterial pr essure, 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 twitchi ng, tachycardia (rate of more than 180) and hypertension (diastolic bl ood pressure of more than 110 mm Hg) each in 44% of cases. Conclusion: Although 3,4-DAP reversed the hypotensive and negative inotropic effe cts of verapamil toxicity, it failed to improve survival and resulted in several complications including muscle twitching, tachycardia, and hypertension.