Models of Cardiovascular Disease: Measurement of Arrhythmogenic/Antiarrhythmic Activity in the Guinea Pig

Philippe Guillaume1, Daniel Provost1, Pierre Lacroix1

1 Porsolt and Partners Pharmacology, Boulogne‐Billancourt, France
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.1
DOI:  10.1002/0471141755.ph0501s44
Online Posting Date:  March, 2009
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Abstract

The protocols described in this unit are used to assess the effects of new chemical entities on arrhythmias in the guinea pig. In the anesthetized guinea pig, arrhythmias are induced by a slow intravenous infusion of digoxin, which provokes extrasystoles, ventricular tachyarrhythmias, and ultimately cardiac arrest. Imipramine precipitates the occurrence of arrhythmias, whereas propranolol shows protection against them. Curr. Protoc. Pharmacol. 44:5.1.1-5.1.5. © 2009 by John Wiley & Sons, Inc.

Keywords: cardiovascular disease; arrhythmias; digoxin

     
 
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Table of Contents

  • Introduction
  • Basic Protocol: Measuring Digoxin-Induced Arrhythmias in the Guinea Pig
  • Commentary
  • Literature Cited
  • Tables
     
 
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Materials

Basic Protocol: Measuring Digoxin-Induced Arrhythmias in the Guinea Pig

 Materials
  • Male Hartley guinea pigs weighing 250 to 270 g at the beginning of the experiment
  • 150 mg/ml urethane anesthesia (Sigma)
  • 50 IU/ml heparin in sterile 0.9% (w/v) NaCl
  • 4 mg/ml imipramine hydrochloride (Sigma)
  • 0.8 mg/ml propranolol (Sigma)
  • Test compound(s)
  • 240 µg/ml digoxin (Procter and Gamble)
  • Polypropylene cages with 191-in.2 (1232-cm2, 28 × 44-cm) floor area
  • Animal balance accurate to 1 g (e.g., Sartorius)
  • 0.86-mm-i.d., 1.27-mm-o.d. catheter
  • 4.0 silk ligatures
  • Blood pressure recorder (e.g., TA 240, Gould Instrument Systems) equipped with:
    • Pressure processor
    • Isolated physiologic pressure transducer
  • Electrocardiograph (Burdik model; Siemens)
  • Programmable multiple-syringe low-flow infusion pump (Harvard Apparatus)
  • 1- and 2-ml syringes
  • 25-G, 5/8-in. Luer Lock needles
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Literature Cited

Literature Cited
    Attree, T., Sawyer, P., and Turnbull, J. 1972. Interaction between digoxin and tricyclic antidepressants in the rat. Eur. J. Pharmacol. 19:294-296.
    Braso, A., Cartheuser, C.F., Brun, R., Anglada, L.L., Sacristan, A., and Ortiz, J.A. 1992. Comparative study on the minimum lethal dose and cardiotoxic effects of sifaprazine, delfaprazine, imipramine and amitriptyline in three animal species. Behav. Pharmacol. 3:66-72.
    Caillard, C.G. and Louis, J.C. 1980. Assessment of antiarrhythmic drugs in experimental pharmacology. Methods Find. Exp. Clin. Pharmacol. 2:223-252.
    Hermansen, K. 1970. Evidence for adrenergic mediation of ouabain-induced arrhythmias in the guinea-pig. Acta Pharmacol. Toxicol. 28:57-63.
    James, T.N. and Nadeau, R.A. 1963. The chronotropic effects of digitalis studied by direct perfusion of the sinus node. J. Pharmacol. Exp. Ther. 139:42-52.
    Sekiya, A. and Vaughan-Williams, E.M. 1963. The effects of pronethalol, dichloroisoprenaline and disopyramide on the toxicity to the heart of ouabain and anaesthetics. Br. J. Pharmacol. 21:462-472.
    Watanabe, Y. and Dreifus, L.S. 1966. Electrophysiologic effects of digitalis on A-V transmission. Am. J. Physiol. 211:1461-1466.
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