Because of its positive inotropic effects that are independent of cyclic AMP, insulin was compared to epinephrine and glucagon as a novel treatment for cardiac toxicity from verapamil. Twenty-four α-chloralose-anesthetized mongrel canines of either sex were instrumented to monitor standard hemodynamic and cardiodynamic parameters and maximum elastance at end systole, via the transit-time technique, as our index of contractility. Toxicity was induced by 0.1 mg/kg/min of verapamil (i.v.), until 50% reduction in mean arterial blood pressure or complete AV dissociation for 30 min. This was followed by continuous infusion of 1.0 mg/kg/hr of verapamil during one of four treatment protocols: 1) control (0.9% NaCl, 2.0 ml/min); 2) epinephrine (1.0 μg/kg/min); 3) hyperinsulinemic-euglycemic (HIE) clamp (recombinant insulin at 4.0 U/min with 20% dextrose, arterial glucose clamped); or 4) glucagon (0.2-0.25-mg/kg bolus infusion followed by 150- μg/kg/min infusion). Treatments were continued until death or 240 min after which time surviving animals received a 3.0-mg/kg additional bolus of verapamil. Verapamil decreased all hemodynamic parameters during titration. All controls died within 85 min. All treatments tended to improve hemodynamics; however, HIE significantly improved maximum elastance at end systole, left ventricular end diastolic pressure and coronary artery blood flow vs. other treatments (P < .05, repeated measures). Glucagon transiently restored sinus rhythm (four animals), but in all cases reverted to A-V dissociation, coincident with sharp decreases in circumflex artery blood flow and contractility. Hyperinsulinemic-euglycemic significantly improved survival postbolus: C, 0%; epinephrine, 33%; HIE, 100%; and glucagon, 0% (P < .05, log rank statistic). HIE is a superior treatment for severe verapamil toxicity in the anesthetized canine and its ability to sustain survival appears to result from its positive inotropic effects.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Dec 8 1993|
ASJC Scopus subject areas
- Molecular Medicine