Acute coronary artery occlusion-reperfusion arrhythmias in pigs: Antiarrhythmic and antifibrillatory evaluation of verapamil, nifedipine, prenylamine and propranolol

Bergey, James L.; Wendt, Robert L.; Nocella, Karen; McCallum, J.

doi:10.1016/0014-2999(84)90516-8

Cited by 30 publications

(7 citation statements)

References 31 publications

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“…*) Preliminary results were presented at the International Symposium on Calcium entry blockers and tissue protection, Rome, 1984, at the 59th Meeting of the Deutsche Physiologische Gesellschaft, Dortmund, 1984, at the 50th meeting of the Deutsche Gesellschaft ffir Herz-und Kreislaufforschung, Mannheim, 1984, and at the IXth European Congress of Cardiology, Dfisseldorf, 1984. It has been known since 1968 (27) that the pretreatment of dogs with the calcium antagonist verapamil reduces the incidence of ischemia-induced arrhythmias. So far, the antiarrhythmic efficacy of some calcium antagonists during acute coronary artery occlusion has been confirmed (1,4,10,11,12,17,26) but their mode of action has still not been clarified exactly.…”

Section: Introductionmentioning

confidence: 98%

Effects of the calcium antagonist gallopamil on the increase of myocardial extracellular potassium activity during LAD occlusion in dogs

Budden¹,

Kirchengast²,

Zhang³

et al. 1987

Basic Res Cardiol

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It has been implied that the increase of myocardial extracellular potassium activity [( K+]e) in the early stage of acute myocardial ischemia is a major cause of the increased likelihood of arrhythmia after acute coronary artery occlusion. There is also experimental evidence that some calcium antagonists reduce the occurrence of ischemia-induced early ventricular arrhythmias. In order to clarify the antiarrhythmic effect of gallopamil during the early phase of acute LAD occlusion, the influence of this calcium antagonist on the time course of [K+]e during acute ischemia was measured in open-chest anesthetized dogs using a K+-selective surface multielectrode. The regional myocardial blood flow was determined with 9 micron radioactive tracer microspheres. After application of gallopamil (bolus 25 micrograms/kg and infusion 2.5 micrograms/kg.min for 30 min) the maximal and mean rate of rise of [K+]e as well as the plateau of [K+]e reached during ischemia were significantly diminished compared with the control occlusions. 90 min after gallopamil, the rate of rise of [K+]e as well as the plateau of [K+]e reached were still significantly reduced, but 180 min after the gallopamil application, no significant differences between the time course of [K+]e and that of the two control occlusions could be found. Gallopamil significantly elevated myocardial blood flow in the non-ischemic area, but did not influence blood flow in the ischemic region. While collateral perfusion remains unchanged, the slowed and reduced increase of myocardial [K+]e during acute coronary artery occlusion may be an important component of the antiarrhythmic effect of gallopamil during early ischemia.

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Section: Introductionmentioning

confidence: 98%

Effects of the calcium antagonist gallopamil on the increase of myocardial extracellular potassium activity during LAD occlusion in dogs

Budden¹,

Kirchengast²,

Zhang³

et al. 1987

Basic Res Cardiol

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“…Negative (e.g., Verdouw & Wolffenbuttel, 1983;Coker & Parratt, 1985;Curtis et al, 1985a) and positive (e.g., Fagbemi & Parratt, 1981;Bergey et al, 1984;Endo et al, 1985) results have been obtained, and no clear pattern has emerged. We have attempted to resolve this issue by using the conscious rat preparation in conjunction with in vitro experiments in the same way that we examined the optical enantiomers of verapamil (Curtis & Walker, 1986).…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Curtis

Walker

1988

British J Pharmacology

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1 Nifedipine and DHM9 (carboxymethyl methyl 1,4-dihydro-2,6-dimethyl-443-nitrophenyl)-3,5-pyridinedicarboxylate) were studied for their effects on arrhythmias resulting from regional myocardial ischaemia in conscious rats, and for their effects on left ventricular developed pressure in vitro.2 Nifedipine possessed antiarrhythmic activity at a high dose of 10mgkg-' i.v., but not at 0.5 or 2mgrkg-. Ventricular fibrillation (VF), tachycardia (VT), and ventricular premature beats (VPB) were all attenuated to a similar degree; nifedipine did not have a selectivity of action for high frequency arrhythmias. 3 Before coronary occlusion, the three doses of nifedipine reduced arterial blood pressure by a similar magnitude, indicating a similar (maximal) degree of systemic vasodilatation. The reductions in blood pressure were accompanied by reflex tachycardia. Heart rate and blood pressure did not correlate with the incidence or severity of arrhythmias. 4 DHM9 had no influence on arrhythmias, haemodynamic variables or the ECG, even at 20mgkg-1i.v.5 Nifedipine concentration-dependently reduced contractility in perfused paced (5 Hz) rat ventricles in vitro. Raising the concentration of K+ in the perfusion fluid from 3 to l0mequiv.l-P increased the potency (-log1o EC50) of nifedipine up to four fold, and caused a significant depression in excitability. 6 DHM9 at up to 3 x 10 5M had no significant influence on ventricular contractility in vitro. 7 The results provided indirect evidence in support of the hypothesis that calcium antagonists inhibit ischaemia-induced arrhythmias by virtue of inhibition of the slow inward current (Ij) in the ischaemic ventricular myocardium.

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“…Coker & Parratt (1985) and Sheehan & Epstein (1982) have also found no protection by nifedipine against ventricular fibrillation occurring during reperfusion in anaesthetized open chest dogs. However, Bergey et al (1984) showed that nifedipine produced a slight dose-dependent decrease in the incidence of ventricular fibrillation in anaesthetized pigs, but this protection was accompanied by a significant increase in ectopic activity.…”

Section: Discussionmentioning

confidence: 94%

Nifedipine effects in severe myocardial ischaemia in the dog due to left anterior descending coronary occlusion with left circumflex coronary artery constriction

Szekeres

Udvary

Végh

1987

British J Pharmacology

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1 The effects of nifedipine were studied in a model of local myocardial ischaemia, comprising anaesthetized thoracotomized dogs in which a critical constriction of the left circumflex coronary artery (LCX) was combined with sudden occlusion of the left anterior descending coronary artery (LAD). Since more than one coronary artery is involved in ischaemic heart disease, the model seems to reflect the clinical situation very closely. 2 In this model, infusion of 1 jig kg-' min-' nifedipine increased myocardial blood flow within the stenosed area served by the LCX as well as in the myocardial region supplied by the LAD, mainly in the subepicardium. Accordingly, the drug reduced ischaemic ST-segment elevation only in the epicardium. 3 It is suggested that nifedipine directed flow to the sub-epicardium of the ischaemic area by improving the collateral circulation. This redistribution of flow resulted in a decrease in the endo/ epicardial flow ratio. 4 Nifedipine did not change the inhomogeneity of electrical activation indicating that it has no effect on the ischaemia-induced conduction delay. At the same time nifedipine was not able to reduce either the number ofextrasystoles appearing in the early postocclusion and reperfusion phase or the incidence of ventricular fibrillation occuring mainly during reperfusion.

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Acute coronary artery occlusion-reperfusion arrhythmias in pigs: Antiarrhythmic and antifibrillatory evaluation of verapamil, nifedipine, prenylamine and propranolol

Cited by 30 publications

References 31 publications

Effects of the calcium antagonist gallopamil on the increase of myocardial extracellular potassium activity during LAD occlusion in dogs

Effects of the calcium antagonist gallopamil on the increase of myocardial extracellular potassium activity during LAD occlusion in dogs

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

Nifedipine effects in severe myocardial ischaemia in the dog due to left anterior descending coronary occlusion with left circumflex coronary artery constriction

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