Short incubation with 7-oxo-prostacyclin induces long lasting prolongation of repolarisation time and effective refractory period in rabbit papillary muscle preparation.
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-prostacyclinephedrine (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 X 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 X 10(-6) mol.litre-1. Pretreatment of rabbits with 7-oxo-PgI2, 50 micrograms.kg-1 intramuscularly, 48 h before the experiments prolonged effective refractory period v 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.
Szekeres
L
L
Department of Pharmacology, Szent-Gvörgyi University Medical School, Szeged, Hungary.
Németh
M
M
Papp
J G
JG
Udvary
E
E
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004558:Electric Stimulation; D004809:Ephedrine / Q000031:analogs & derivatives / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D005260:Female; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D010210:Papillary Muscles / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013997:Time Factors
D010975:Platelet Aggregation Inhibitors; C053676:7-oxo-prostaglandin I2-ephedrine; D011464:Epoprostenol; D004809:Ephedrine