The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion‐induced arrhythmias in anaesthetized rats

Abstract

In male rats, anaesthetized with pentobarbitone, ligation of the main left coronary artery causes an early phase of ventricular arrhythmias which last about 30 min. In approximately 60% of control animals, ventricular fibrillation occurs but since spontaneous reversion to sinus rhythm may occur, mortality is of the order of 30%. When administered intravenously 15 min prior to ligation, verapamil (0.01 and 0.05 mg kg−1), prenylamine (0.5 mg kg−1), flunarizine (0.1, 0.25, 0.5 and 1.0 mg kg−1) and cinnarizine (0.25, 0.5 and 1.0 mg kg−1) protected against these arrhythmias. Higher doses of verapamil (0.1 and 0.5 mg kg−1), prenylamine (5 mg kg−1) and flunarizine (2.5 mg kg−1) did not afford a similar protection and mortality was increased to or above control values. Death was due in prenylamine‐treated rats to atrioventricular block leading to asystole whereas in those administered verapamil or flunarizine it was a consequence of persistent ventricular fibrillation. Prior to ligation, a sustained fall in mean arterial blood pressure was observed only following the administration of the highest doses of prenylamine, flunarizine and cinnarizine. Heart rate was reduced by administration of only the highest dose of prenylamine. These studies show that although the four calcium antagonists studied, i.e. verapamil, prenylamine, flunarizine and cinnarizine do suppress ischaemia‐induced arrhythmias, this protective effect may be limited to a narrow concentration range.

The mechanism of action of the optical enantiomers of verapamil against ischaemia‐induced arrhythmias in the conscious rat

“…In our experience (Curtis et al, 1984) anaesthetized rats are much more sensitive to the haemodynamic effects of phenethylamine calcium antagonists than conscious rats. In addition, according to Fagbemi et al (1984), in anaesthetized rats, ( ± )-verapamil possesses a bell-shaped dose-response curve for the reduction of occlusion-induced arrhythmias. Therefore, since D-600 and verapamil possess qualitatively similar properties, the conclusions of Mueller & Wilsmann were by no means unequivocal.…”

Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and extent of infarction following reperfusion in conscious baboons.

“…The radioactive microsphere technique as previously described by Domenech et al 32 and used in this laboratory 34 *-30 was used to measure regional myocardial blood flow. In this study, 15 ± 1 /xm microspheres labeled with 14l Ce, "Nb, "Sr, "Sc,…”

The mechanism of action of calcium antagonists on arrhythmias in early myocardial ischaemia: studies with nifedipine and DHM9

“…There has been considerable disagreement concerning their antiarrhythmic activity in the setting of early regional myocardial ischaemia. Phenethylalkylamines such as verapamil have been shown to possess marked antiarrhythmic actions by some investigators (e.g., Kaumann & Aramendia, 1968;Bren et al, 1982;Bergey et al, 1984), but not by others (e.g., Mertz & Kaplan, 1982;Mueller & Wilsmann, 1982;Fagbemi et al, 1984). In the case of verapamil, the 1 Present address and address for correspondence: Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London SEI 7EH. minimum effective dose is approximately 0.5 mgkg-' in acutely prepared anaesthetized animals and 2mgkg-1 in conscious animals (Curtis et al, 1984).…”