Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine.
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 alpha-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 micrograms/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-micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kline
J A
JA
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina.
Tomaszewski
C A
CA
Schroeder
J D
JD
Raymond
R M
RM
D000758:Anesthesia; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004573:Electrolytes / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D005934:Glucagon / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D015203:Reproducibility of Results; D014700:Verapamil / Q000633:toxicity*
D000931:Antidotes; D001786:Blood Glucose; D004573:Electrolytes; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D005934:Glucagon; D014700:Verapamil; D004837:Epinephrine