Hemodynamic effects of 3,4-diaminopyridine in a swine model of verapamil toxicity.
OBJECTIVE
3,4-Diaminopyridine (3,4-DAP) may reverse the hemodynamic effects of severe verapamil toxicity.


METHODS
A nonblinded acute animal preparation.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Plewa
M C
MC
Western Pennsylvania Hospital.
Martin
T G
TG
Menegazzi
J J
JJ
Seaberg
D C
DC
Wolfson
A B
AB
D015761:4-Aminopyridine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000077770:Amifampridine; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D011041:Poisoning / Q000188:drug therapy; D015221:Potassium Channels / Q000187:drug effects*; D013552:Swine; D014700:Verapamil / Q000506:poisoning*
D015221:Potassium Channels; D015761:4-Aminopyridine; D014700:Verapamil; D000077770:Amifampridine