title: Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine.
abstract: 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)
authors.affiliation: Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: J A
authors.initials: JA
authors.lastname: Kline
authors.forename: C A
authors.initials: CA
authors.lastname: Tomaszewski
authors.forename: J D
authors.initials: JD
authors.lastname: Schroeder
authors.forename: R M
authors.initials: RM
authors.lastname: Raymond
mesh_terms: 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*
chemical_list: D000931:Antidotes; D001786:Blood Glucose; D004573:Electrolytes; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D005934:Glucagon; D014700:Verapamil; D004837:Epinephrine