AJP - Heart and Circulatory Physiology, Vol 249, Issue 1 57-H63, Copyright © 1985 by American Physiological Society
Prostaglandin involvement in hypersensitivity of ischemic hearts to arrhythmogenic influence of ouabain
M. P. Moffat, M. Karmazyn and G. R. Ferrier
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).
