ANTIARRHYTHMIC, HAEMODYNAMIC AND METABOLIC EFFECTS OF 3α‐AMINO‐5α‐ANDROSTAN‐2β‐OL‐17‐ONE HYDROCHLORIDE IN GREYHOUNDS FOLLOWING ACUTE CORONARY ARTERY LIGATION

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ST‐segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open‐chest anaesthetized dogs. This was greatly reduced by the prior administration of the antidysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the extent and degree of myocardial ischaemia or to prevention of K+ egress from ischaemic cells.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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The Antidysrhythmic Aminosteroid, Org 6001, Reduces the St‐segment Elevation Produced by Coronary Occlusion in the Dog

Marshall¹,

Parratt²

1977

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“…Org 6001 (3a-amino-5x-androstan-2p-ol-17-one HCI) protects against arrhythmias induced by coronary artery ligation after both acute (Marshall & Parratt, 1975) and prolonged oral pretreatment (Kane, Lepran, McDonald, Parratt & Szekeres, 1980). It may, therefore, be a useful prophylactic agent in preventing sudden cardiac death resulting from reinfarction.…”

Section: Introductionmentioning

confidence: 99%

Antiarrhythmic Effects of Org 6001 in Rats: Correlation With Plasma and Tissue Drug Concentrations

Kane¹,

McDonald²,

Parratt³

et al. 1982

1 The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. 2 Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10,20,50 and 100 mg/kg given 1 h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0-30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. 3 A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. 4 The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time.5 No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. 6 The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug.

“…Marshall & Parratt (1975) (H. Jansen, personal communication). Org 6001 has been categorized as a class 1 antidysrhythmic drug on the basis of its ability to reduce the maximum rate of depolarization of phase zero (MRD) of the rabbit cardiac muscle action potential (Salako, Vaughan Williams & Wittig, 1976).…”

Section: Introductionmentioning

confidence: 99%

COMPARATIVE ELECTROPHYSIOLOGICAL EFFECTS OF Org 6001, A NEW ORALLY ACTIVE ANTIDYSRHYTHMIC AGENT, AND LIGNOCAINE ON HUMAN VENTRICULAR MUSCLE

Kane

1980

The electrophysiological effects of Org 6001, a new orally active antidysrhythmic agent, have been compared with those of lignocaine on the human ventricular action potential in vitro. 2 Org 6001 (4 to 16 mg/l) greatly reduced the maximum rate of depolarization (MRD) of the human ventricular action potential but had no effect on resting membrane potential or action potential amplitude. 3 The action potential duration at the 50% repolarization level, but not at the 90% repolarization level, was significantly reduced by Org 6001. The absolute refractory period was unchanged. 4 Lignocaine, at a concentration (4 mg/l) within the therapeutic range, had no significant effect on any measured parameter, either in muscle exposed to a normal (4.0 mM) or high (5.4 mM) extracellular potassium concentration ([K+]j. 5 Higher concentrations of lignocaine (8 to 16 mg/i) did, however, reduce MRD at both [K+].without changing resting membrane potential or action potential amplitude. The action potential duration was decreased slightly by these higher concentrations of lignocaine whilst the absolute refractory period was lengthened. 6 Org 6001 was found to be more potent than lignocaine in reducing MRD but, unlike lignocaine, the absolute refractory period was not prolonged. These compounds, therefore, differed in their electrophysiological effects on human ventricular muscle although both are characterized as being class I antidysrhythmic drugs.