Development of a severe model of early coronary artery ligation-induced dysrhythmias in the anaesthetized rat.

1. The potential use of catecholamines to increase the severity of dysrhythmias evoked by coronary artery ligation in the anaesthetized rat was investigated. Drugs were given intravenously prior to ligation. 2 Pressor doses of adrenaline (5 microgram/kg) noradrenaline (1 microgram/kg) phenylephrine (5-10 microgram/kg), and angiotensin (0.25 microgram/kg) conferred protection against the development of dysrhythmias. 3 Atropine (1 mg/kg) increased mortality from ventricular fibrilloflutter (VF) and abolished the protective effects of phenylephrine (10 micrograms/kg). 4 Administration of isoprenaline (10 microgram/kg) significantly increased the incidence of and the mortality from VF. 5 The order of antidysrhythmic drug potency of Org 6001 (1-10 mg/kg), disopyramide (2-10 mg/kg) and practolol (2-10 mg/kg) was similar in both the standard (without isoprenaline) and modified (with isoprenaline) models. 6 Use of the modified method for antidysrhythmic screening purpose allows demonstration of statistically meaningful results with the use of relatively few animals. 7 Comparison of the pattern of VF in the rat heart induced by various means suggests that the diagnosis of ventricular fibrillation can be made with more confidence in the modified method compared to the standard method.