A protective effect of verapamil on hypoxic heart muscle

Nayler, Winifred G.; Grau, Aleyda; Slade, A.M.

doi:10.1093/cvr/10.6.650

Cited by 162 publications

(36 citation statements)

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“…For example, verapamil does not exhibit a linear log dose-response curve with respect to protection against myocardial enzyme leakage during hypoxia (Nayler et al, 1976) or ischaemia (Yamamoto et al, 1983) nor against the calcium paradox (Hearse et al, 1980). Furthermore, the ability of both prenylamine (Manning et al, 1982) and nifedipine (Selwyn et al, 1979) to reduce the extent of myocardial ischaemic damage is lost at higher concentrations.…”

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confidence: 99%

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

Fagbemi

Kane

McDonald

et al. 1984

British J Pharmacology

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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.

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Section: )mentioning

confidence: 99%

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

Fagbemi

Kane

McDonald

et al. 1984

British J Pharmacology

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“…Improvement of depressed membrane responses of ischemic myocardial cells by verapamil and D-600 may be related to either hemodynamic and metabolic effects of the drugs30' 31 or to a direct electrophysiologic action. Verapamil has been shown to reduce the extent of ischemic injury after coronary artery ligation.30 However, it probably will not have a similar effect when administered 3-7 days after myocardial infarction, as in the present study.…”

Section: Mechanisms Of the Antiarrhythmic Effect Of Verapamil And D-6mentioning

confidence: 99%

Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the "slow channel".

El‐Sherif¹,

Lazzara²

1979

Circulation

111

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SUMMARY Reentrant ventricular arrhythmias (RVA) were analyzed in dogs 3-7 days after ligation of the anterior descending coronary artery using averaged "composite" recordings of electrical activity of reentrant pathways (RP) from the epicardial surface of the infarction zone (IZ). Verapamil (V) and D-600 (D) (0.2-0.5 mg/kg i.v.) resulted in slight-to-moderate improvement of conduction in RP with abolition of spontaneous RVA and RVA initiated by premature depolarizations. The effect of V was not blocked by pretreatment with propranolol (0.5 mg/kg i.v.). Using a standard microelectrode technique aad strips of epicardial muscle from the IZ, D (0.5-1 X 10-6 g/ml) slightly improved the upstroke velocity and membrane responses of depressed ischemic cells. In contrast, tetrodotoxin (5 X 10-7 g/ml) further depressed or abolished action potentials of ischemic cells. We conclude: 1) the moderate antiarrhythmic effect of V and D on RVA is the result of improved conduction in RP; 2) this action is partly explained by improvement of a depressed sodium channel and is not related to catecholamine release; 3) slow-response action potentials play no significant role in the genesis of ischemia-related RVA, which probably results from depression of the fast response.IN THE LATE myocardial infarction period (3-7 days after infarction), the propensity for reentrant ventricular arrhythmias is still maintained. In a recently described canine model, reentrant ventricular arrhythmias were remarkably stable, and averaged recordings of the electrical activity of reentrant pathways could be obtained from the epicardial surface of the infarction zone with a specially designed composite electrode.''3 The canine model was used in both in vivo and in vitro experiments to study the mechanism of action of lidocaine4 I and dipherylhydantoin.6 Both drugs owed their antiarrhythmic effect to selective prolongation of refractoriness and depression of conduction in reentrant pathways in ischemic myocardium.In this study, we analyzed the effects of verapamil and its methoxy derivative, D-600, on electrophysiologic properties of ischemic myocardium and on related reentrant ventricular arrhythmias in both in vivo and in vitro experiments. The effect of D-600 on ischemic myocardial cells is also contrasted with that of tetrodotoxin. Both verapamil and D-600 are thought to act by blocking the slow inward current carried by calcium (Ca++)7 9 and possibly by sodium (Na+).1" It has been suggested that slow conduction in depressed cells," including ischemic myocardium,12 that can lead to reentrant ventricular arrhythmias is a property of the slow response action potential. This study provides a direct evaluation of the role that the Material and MethodsIn Vivo ExperimentsAdult mongrel dogs were studied 3-7 days after ligation of the left anterior descending artery just distal to the anterior septal branch. In all dogs, a transmural infarction was evident on gross postmortem examination. Recordings were obtained from the epicardial surface of the infarction zo...

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“…They have been demonstrated in numerous well-founded works, in part on isolated preparations and in part on animals äs well äs on sick and healthy people [11,15,16,24,25,26,27]. FLECKENSTEIN [12] revealed the mechanism of the cardiotoxic effect of adrenergics and the possibility of antagonizing this effect with Verapamil (Fig.…”

Section: Discussionmentioning

confidence: 99%

Does the administration of the calcium-antagonist verapamil in tocolysis with beta-sympathicomimetics still make sense?

Strigl¹,

Pfeiffer²,

Erhardt³

et al. 1981

Journal of Perinatal Medicine

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A protective effect of verapamil on hypoxic heart muscle

Cited by 162 publications

References 0 publications

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

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

Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the "slow channel".

Does the administration of the calcium-antagonist verapamil in tocolysis with beta-sympathicomimetics still make sense?

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