Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine

Jeffrey Kline, C. A. Tomaszewski, J. D. Schroeder, R. M. Raymond

Research output: Contribution to journalArticle

103 Citations (Scopus)

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 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 languageEnglish (US)
Pages (from-to)744-750
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number2
StatePublished - 1993
Externally publishedYes

Fingerprint

Antidotes
Verapamil
Canidae
Insulin
Glucagon
Epinephrine
Systole
Hemodynamics
Arterial Pressure
Therapeutics
Glucose
Chloralose
Heart Block
Glucose Clamp Technique
Clinical Protocols
Cyclic AMP
Coronary Vessels
Arteries
Blood Pressure

ASJC Scopus subject areas

  • Pharmacology

Cite this

Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine. / Kline, Jeffrey; Tomaszewski, C. A.; Schroeder, J. D.; Raymond, R. M.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 267, No. 2, 1993, p. 744-750.

Research output: Contribution to journalArticle

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