The Effects of Sodium Channel Inhibitors on Early Arrhythmias Associated with Acute Myocardial Ischaemia

Marshall, Richard; Winslow, E.

doi:10.1007/978-1-349-06260-7_15

Cited by 13 publications

(7 citation statements)

References 137 publications

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“…The ability to inhibit the rapid Na+ current in cardiac muscle is one major property responsible for antiarrhythmic activity (class 1 in Vaughan Williams classification; Vaughan Williams, 1970) and such drugs are, in general, effective against early ischaemic arrhythmias (reviewed by Marshall & Winslow, 1982). For example, lignocaine and the aminosteroid Org 6001 are effective in the anaesthetized rat model used in the present studies (Kane, McDonald & Parratt, 1979;Clark et al, 1980).…”

Section: Relevance Off-adrenoceptor Blockadementioning

confidence: 94%

The effect of β‐adrenoceptor blocking agents, with differing ancillary properties, on the arrhythmias resulting from acute coronary artery ligation in anaesthetized rats

Campbell

Parratt

1983

British J Pharmacology

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The effects of several P-adrenoceptor blocking agents, ((+), (-) and (±)-oxprenolol, poxprenolol, practolol, propranolol and timolol) were investigated on the ventricular arrhythmias occurring within the first 30 min of acutely ligating the main left coronary artery in anaesthetized rats. The degree of cardiac and vascular 3-adrenoceptor blockade was also assessed. 2 All the compounds exhibited antiarrhythmic activity under these conditions. The degree of cardiac P-adrenoceptor blockade required for this protection was less for the cardioselective agents, p-oxprenolol and practolol, than for the non-selective 3-adrenoceptor blocking agents. 3 A comparison of the two isomers of oxprenolol demonstrated that the (-)-isomer markedly suppressed ischaemic arrhythmias (ventricular ectopic beats, incidence and duration of ventricular tachycardia and duration of ventricular fibrillation) more effectively than the (+)-isomer. 4 Compounds possessing intrinsic sympathomimetic activity (ISA) caused less marked haemodynamic changes (in equivalent f-blocking doses) than those that did not possess this ancillary property.5 The membrane stabilizing activity of oxprenolol and p-oxprenolol did not appear to contribute to the antiarrhythmic activity of these agents; however, the membrane stabilizing activity of propranolol may contribute to its effectiveness. 6 In all the drugs studied, the main pharmacological property required to suppress early postischaemic arrhythmias is blockade of cardiac f-adrenoceptors.

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Section: Relevance Off-adrenoceptor Blockadementioning

confidence: 94%

The effect of β‐adrenoceptor blocking agents, with differing ancillary properties, on the arrhythmias resulting from acute coronary artery ligation in anaesthetized rats

Campbell

Parratt

1983

British J Pharmacology

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“…No serious cardiovascular side effects have been associated with bidisomide [3]. The efficacy of class I antiarrhythmic agents against ventricular ectopic beats occurring several hours after the onset of myocardial infarction has been established in animal experiments [4,5], but there is some controversy concerning the efficacy of these drugs for early-phase ventricular arrhythmias resulting from myocardial ischemia [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Effects of bidisomide (SC-40230), a new class I antiarrhythmic agent, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats; comparison with mexiletine and disopyramide

Komori

Sano

et al. 1995

Heart Vessels

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We investigated the antiarrhythmic effects of bidisomide (SC-40230), a new class I antiarrhythmic drug, in early-phase ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats. The effects of bidisomide were compared with those of mexiletine (MXT) and disopyramide (DSP), established class I antiarrhythmic drugs. Drugs were administered intravenously, 5 min before induction of coronary occlusion. Bidisomide (5 mg/kg) reduced the number of premature ventricular complexes and the incidence of ventricular tachycardia and ventricular fibrillation similarly to MXT and DSP in rats with ventricular arrhythmias induced by coronary artery occlusion. In rats with ventricular arrhythmias induced by coronary artery reperfusion following a 5-min coronary occlusion, the antiarrhythmic effects of 5 mg/kg of bidisomide were similar to those of the same doses of MXT and DSP. All three drugs significantly slowed the heart rate. Our results suggest that bidisomide may effectively reduce the severity of life-threatening ventricular arrhythmias that occur during acute coronary syndrome.

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“…Different plasma levels of the two compounds might, therefore, account for the differential effects on VFT as seen at different times after dosing. Fibrillation thresholds are increased by sodium-channel blocking agents (Marshall & Winslow 1982;Camm 1984;Almotrefi 1985) and higher levels of Org 7797 (as adjudged from single dosing with 20 mg kg-I) would be expected at 1, as compared with 6 h after dosing. However, in the in-vitro studies on excised papillary muscle, we observed a modest, but statistically significant, reduction in V, , , with no change in resting membrane potential (indicative of a class I action) and this change in V, , , was similar in muscles excised at 1 and 6 h afier the last dose of drug was given.…”

Section: Figmentioning

confidence: 99%

Antiarrhythmic, Electrophysiological and Haemodynamic Effects of Prolonged Oral Dosing with Org 7797 in the Anaesthetized Rat

Delbressine¹,

Harris

Kane

et al. 1992

Journal of Pharmacy and Pharmacology

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The antiarrhythmic, electrophysiological and haemodynamic effects of chronic oral administration of Org 7797 ((16 alpha,17 beta)-17-methylamino-oestra-1,3,5(10)-triene-3, 16-diol-(Z)-2-butonedioate) were studied in rats. During dosing (10 mg kg-1 twice a day for 10 days) no effects on the electrocardiogram, monitored in conscious animals, were observed despite modest reductions (15-18%) in the maximum rate of depolarization of papillary muscle excised 1 or 6 h after completion of the dosing regime. Following anaesthesia, Org 7797 reduced the severity of arrhythmias induced by coronary artery occlusion and prevented the accompanying decrease in the ventricular fibrillation threshold (VFT) at 1 h after completion of dosing. By 6 h the effect on VFT had waned but protection against ischaemia-induced arrhythmias was retained despite a substantial decrease in Org 7797 plasma levels. Drug treatment did not modify arterial blood pressure, heart rate or stroke volume. We conclude that Org 7797 given chronically via the oral route exerts antiarrhythmic actions which may, at least in part, be due to sodium-channel block. In addition, our results suggest the presence of an active metabolite. The protective effects of Org 7797 were seen in the absence of electrocardiographic or haemodynamic changes suggesting that multiple oral doses of Org 7797 do not compromise normal cardiac function.

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The Effects of Sodium Channel Inhibitors on Early Arrhythmias Associated with Acute Myocardial Ischaemia

Cited by 13 publications

References 137 publications

The effect of β‐adrenoceptor blocking agents, with differing ancillary properties, on the arrhythmias resulting from acute coronary artery ligation in anaesthetized rats

The effect of β‐adrenoceptor blocking agents, with differing ancillary properties, on the arrhythmias resulting from acute coronary artery ligation in anaesthetized rats

Effects of bidisomide (SC-40230), a new class I antiarrhythmic agent, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats; comparison with mexiletine and disopyramide

Antiarrhythmic, Electrophysiological and Haemodynamic Effects of Prolonged Oral Dosing with Org 7797 in the Anaesthetized Rat

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