Mc. Plewa et al., HEMODYNAMIC-EFFECTS OF 3,4-DIAMINOPYRIDINE IN A SWINE MODEL OF VERAPAMIL TOXICITY, Annals of emergency medicine, 23(3), 1994, pp. 499-507
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.