Prostaglandin involvement in hypersensitivity of ischemic hearts to arrhythmogenic influence of ouabain.
Arrhythmias were produced by ouabain (2.7 X 10(-7) M) in isolated perfused guinea pig hearts. In control hearts the average time to onset of arrhythmias following exposure to ouabain was approximately 35 min. Ligation of the left anterior descending coronary artery significantly shortened the time to arrhythmias to about 15 min. This effect of ligation was attenuated significantly by pretreating the hearts with acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs. In contrast, the protective influence of ASA was reversed by either prostaglandin (PG) E2, PGF2 alpha, or PGI2 (2.8 X 10(-9) M). When PGE2 or PGI2 were present in the absence of ASA, the time to arrhythmias following ouabain administration was significantly shortened. PGF2 alpha had no effect in these experiments. The sensitivity was enhanced significantly by treatment with arachidonic acid. This effect was reduced by treatment with ASA or indomethacin. Prostaglandin production during the experiments was estimated by monitoring release of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin. Abbreviation of time to arrhythmias by ligation was greatest in hearts that released large amounts of 6-keto-PGF1 alpha and least in those that released low amounts. These results suggest that coronary ligation potentiates the arrhythmogenic effects of ouabain by a mechanism probably mediated by prostaglandin(s).
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control; D001241:Aspirin / Q000494:pharmacology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000601:surgery; D015237:Dinoprost; D015232:Dinoprostone; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008026:Ligation; D008297:Male; D010042:Ouabain / Q000633:toxicity*; D010477:Perfusion; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D013997:Time Factors
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D010042:Ouabain; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin