A direct role of endogenous prostaglandins in reperfusion-induced cardiac arrhythmias.
The possible role of prostaglandins (PG) in arrhythmias associated with ischemia and reperfusion was studied in isolated, superfused canine Purkinje tissues. Ischemic conditions caused partial depolarization and decrease of excitability. Neither inhibition of PG synthesis (ibuprofen, 30 micrograms/mL) nor addition of exogenous PGF2 alpha (1 ng/mL) modified responses to "ischemia." Reperfusion with normal Tyrode's solution stimulated PG production (measured as 6-keto-PGF1 alpha) and induced a series of electrophysiological events. Under control conditions, Purkinje fibres rapidly repolarized. Subsequently, these tissues began to depolarize and oscillatory afterpotentials appeared. Purkinje tissues depolarized further and became temporarily inexcitable. Return of activity was associated with depolarization-induced automaticity. Ibuprofen prevented reperfusion-stimulated PG release. Ibuprofen also increased the magnitude of early repolarization and greatly attenuated subsequent depolarization. Depolarization-induced automaticity was not observed under these conditions; however, oscillatory afterpotentials were not abolished by ibuprofen. Addition of PGF2 alpha to "ischemic" and reperfusion solutions in the presence of ibuprofen restored the arrhythmogenic responses. We conclude that release of endogenous prostaglandins contributes to electrophysiological changes elicited by reperfusion in canine Purkinje fibres.
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
M P
MP
Moffat
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Ferrier
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Karmazyn
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology; D001241:Aspirin / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis / Q000502:physiology*; D004285:Dogs; D006329:Heart Conduction System / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D011690:Purkinje Fibers / Q000187:drug effects / Q000378:metabolism*
D015237:Dinoprost; D001241:Aspirin; D007052:Ibuprofen