Study objective - To determine whether the long lasting protection from early postocclusion and reperfusion arrhythmias induced by 7-oxo-prostacyclin is due to an anti-ischaemic effect alone or in combination with direct membrane effects.Design - The study was performed on electrically stimulated isolated rabbit papillary muscle preparations with or without incubation with a stable prostacyclin analogue, 7-oxo-prostacyclin-ephedrine (7-oxo-PgI2). In some experiments, rabbits were pretreated with 7-oxo-PgI2.Measurements and results - Marked prolongation of action potential duration (APD90) and effective refractory period developed 2 h after 20 min incubation with and subsequent washout of 7-oxo-PgI2, 1.1 × 10-8 mol.litre-1. The same occurred if incubation with 7-oxo-PgI2 was maintained throughout the experiment. The only other change was a small diminution in amplitude of the action potential. During the 20 min incubation period neither APD90 nor effective refractory period was affected and only a transitory increase in the maximum rate of depolarisation, disappearing after washout, was seen. During the 4 h observation period there were no changes in the control preparations. The long lasting electrophysiological changes induced by 7-oxo-PgI2 were not affected by 60 min incubation with indomethacin, 2.8 × 10-6 mol.litre-1. Pretreatment of rabbits with 7-oxo-PgI2, 50 μg.kg-1 intramuscularly, 48 h before the experiments prolonged effective refractory period ν, untreated controls.Conclusions - 7-oxo-PgI2 induces prolongation of APD90 and effective refractory period in adequately oxygenated normal papillary muscles as well as in ischaemic hearts. Therefore a direct membrane effect may contribute to its antiarrhythmic action, as well as an indirect anti-ischaemic effect. Such a direct effect is unlikely to be related to activation of the degradation products of the arachidonic acid cascade since it was not influenced by indomethacin.
- Effective refractory period
- Repolarisation time
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)