Calcium antagonists prevent early post-infarction ventricular fibrillation

1 The effects of (1-{1-[(6-methoxyl)-naphth-2-yl]}-propyl-2-(1-piperidine)-acetyl-6,7-dimethyoxy-1,2,3,4-tetra-hydroisoquinoline) were studied on mechanical and electrical activities, and intracellular free calcium ([Ca2+]i) of isolated cardiac tissues in order to investigate its spectrum and mechanisms of action in the heart. Its antiarrhythmic and haemodynamic effects in pentobarbitone-anaesthetized rats subjected to coronary artery ligation were also evaluated. 2 CPU-23 at 10-6 10-4 M markedly inhibited slow action potential characteristics in guinea-pig papillary muscles and pace-maker action potential of rabbit sinoatrial node. It affected fast action potential only at 10-4 M. None of the effects of CPU-23 was reversed by washout for up to 2 h.3 Like nifedipine and diltiazem, CPU-23 decreased the heart rate of the isolated perfused heart of the rat. However, in contrast to these two classical calcium antagonists which dose-dependently inhibited the force of contraction, CPU-23 inhibited and stimulated the force of contraction at 10-7-3 x 10-6 M and 10-5 M, respectively. 4 CPU-23 at 10-6 10-5 M inhibited the KCl-induced [Ca2+], increase in the Ca2" medium, but did not affect the caffeine-induced [Ca21], increase in the Ca2'-free medium in isolated ventricular myocytes. 5 CPU-23 at 1-5 mg kg-' reduced dose-dependently ventricular arrhythmias including ventricular ectopic beats, VT and VF as well as mortality during coronary artery ligation. At 2.5-5 mg kg-' it even abolished VF, which was accompanied by 100% survival. 6 It is suggested that CPU-23 has calcium antagonistic properties in cardiac tissues. It selectively blocks the transmembrane influx of extracellular Ca2" through Ca2" channels, thus reducing the heart rate and developed tension, altering the slow action potential characteristics and producing antiarrhythmic effect against ischaemic arrhythmias.

Section: Coronary Artery Ligation In Anaesthetized Ratsmentioning

confidence: 96%

Calcium antagonistic and antiarrhythmic actions of CPU‐23, a substituted tetrahydroisoquinoline

Dong

Sheng

Lee

et al. 1993

“…The class IV agent nifedipine failed to prevent the postligation fall in VFT in a dose reported to reduce the severity of postligation arrhythmias in the rat in the absence of marked or sustained bradycardia or hypotension (Fagbemi & Parratt, 1981). Thandroyen, Higgenson & Opie (1980) found that nifedipine increased VFT of rat isolated perfused heart and attenuated the fall in VFT after ligation but only at concentrations close to those producing disturbances of AV conduction.…”

Section: Discussionmentioning

confidence: 99%

“…A number of known antiarrhythmic agents including membrane stabilizing agents, P-adrenoceptor blocking drugs, agents which prolong action potential duration and drugs which inhibit transmembrane calcium movement have been shown to reduce the severity of the arrhythmias in this model (Clark et al, 1980;Kane & Winslow, 1980;Kane, McDonald & Parratt, 1981;Marshall, Muir & Winslow, 1981a,b;Fagbemi & Parratt, 1981). Using Vaughan Williams' (1974) clasification, these agents will be referred to as class I, II, III and IV respectively.…”

Section: Introductionmentioning

confidence: 99%

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

Marshall¹,

Muir²,

Winslow³

1983

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.

“…Carotid artery pressure and a standard lead II electrocardiogram (ECG) were recorded using a Devices F-132 physiopolygraph. The method of inducing coronary artery occlusion and evaluation of the subsequent arrhythmia has already been described in detail (Clark et al, 1980;Fagbemi & Parratt, 1981).…”

Section: Methodsmentioning

confidence: 99%

The effects of the combined administration of β‐adrenoceptor antagonists and non‐steroidal anti‐inflammatory drugs on ligation‐induced arrhythmias in rats

Fagbemi

1985

Pretreatment of anaesthetized rats with intravenously administered β‐adrenoceptor antagonists or non‐steroidal anti‐inflammatory drugs (NSAIDs) reduced the incidence and severity of ventricular arrhythmia which resulted from acute coronary artery ligation. The β‐adrenoceptor antagonists preferentially suppressed the immediate (Phase 1A) arrhythmia while the NSAIDs suppressed the delayed (Phase IB) arrhythmias. Combined administration of β‐adrenoceptor antagonists and the NSAIDs produced a more pronounced antiarrhythmic effect than either of the drugs alone.