Effects of antiarrhythmic drugs on ventricular fibrillation thresholds of normal and ischaemic myocardium in the anaesthetized rat

Abstract

1 The effects of agents which produce membrane stabilization (class I), Pl-adrenoceptor blockade (class II), prolongation of the cardiac action potential (class III) or inhibition of the slow inward current (class IV) were investigated for their ability to increase the ventricular fibrillation threshold (VFT) or to modify the fall in VFT consequent upon coronary artery ligation in the anaesthetized rat. 2 The class I agent, Org 6001, increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT. 3 The class II agent, metoprolol, failed to increase VFT of normal myocardium but reduced the postligation fall.4 The class III agent, melperone, increased VFT of both normal and ischaemic myocardium whereas the class IV agent, nifedipine failed to influence VFT in either region. 5 Bepridil (class I and IV) was similar to Org 6001 and sotalol (class II and III) in that it increased VFT of normal myocardium and in lower doses reduced the postligation fall in VFT.6 Measurement of VFT before and after coronary artery ligation in the rat constitutes a rapid and reproducible screen to detect antifibrillatory activity. 7 The results also suggest that in the rat, the low currents used (-400ptA) do not release substantial quantities of catecholamines whereas these may be released by coronary artery ligation.

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat

“…Electrically-induced arrhythmias Verapamil and quinidine were tested against electrically-induced arrhythmias in conscious and anaesthetized rats by methods similar to those of Martinez & Crampton (1981) and Marshall et al (1983). Stainless steel electrodes were permanently implanted, 0.3 cm apart, into the left ventricle, and their free ends exteriorised in the neck region.…”

Blockade by antiarrhythmic drugs of glibenclamide‐sensitive K+ channels in Xenopus oocytes

“…Our present results suggest that the suppression of glibenclamide-sensitivie K+ channels may underlie at least partly the mechanism of antiarrhythmic effects of calmodulin-antagonizing antiarrhythmic drugs. In this connection, it is noteworthy that bepridil, a potent calmodulin antagonist, is expected to be clinically effective for ventricular arrhythmia (Marshall et al, 1983;Singh et al, 1985).…”

Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation—tentative prophylactic properties of vagus nerve stimulation on malignant arrhythmias in heart failure

“…VFT is widely used for the study of arrhythmia susceptibility and has been shown to predict the increased and decreased susceptibility of the ventricle to arrhythmias in a range of situations [56, 66, 70]. Some investigators are concerned that VFT does not predict the anti-arrhythmic actions of certain drugs and fails to predict the occurrence of spontaneous arrhythmias [71]. However, Harumi et al [72] have demonstrated that anti-arrhythmic drugs can be classified depending upon their effects on VFT, ventricular refractoriness and electrical restitution properties, indicative of the multiple mechanisms of action of many of these drugs.…”