Role of prostaglandins in the arrhythmogenic effects of ouabain on isolated guinea pig hearts.
We examined the hypothesis that endogenous prostaglandins participate in the arrhythmogenic influence of ouabain in guinea pig hearts. Addition of ouabain (10 ng/ml) resulted in a 5-fold increase in the release of 6-keto-prostaglandin F1 alpha in the coronary effluent. Ten of 13 hearts studied (77%) demonstrated arrhythmic activity with a mean time to the onset of arrhythmias of approximately 35 min. The nonsteroidal antiinflammatory drugs indomethacin and acetylsalicylic acid which significantly inhibited the efflux of 6-keto-prostaglandin F1 alpha also reduced the incidence of arrhythmias to 10 of 30 hearts studied. In those hearts in which arrhythmias occurred, the time to onset was significantly increased to approximately 50 and 55 min for acetylsalicylic acid and indomethacin, respectively. In contrast, exogenous prostaglandin F2 alpha (0.1 and 1 ng/ml) and prostacyclin (0.1 and 10 ng/ml) increased the incidence of arrhythmias to 100% (10 of 10 hearts studied) and decreased the time to onset to approximately 10 min. These prostaglandin pretreatments were also able to reverse the protective actions of both acetylsalicylic acid and indomethacin. Other concentrations (10 ng/ml prostaglandin F2 alpha and 1 ng/ml prostacyclin) had no influence either on the incidence of arrhythmias or their time to onset. Prostaglandin E2 (0.1 ng/ml) produced a modest but not significant decrease in the time to onset of arrhythmias although this concentration was significantly effective in reversing the nonsteroidal antiinflammatory drug effects. The inotropic, chronotropic and coronary constricting actions of ouabain were unaffected either by nonsteroidal antiinflammatory drug or prostaglandin pretreatment. These studies suggest that prostaglandins are involved, at least in part, in the arrhythmogenic actions of ouabain in the isolated guinea pig heart.
Moffat
M P
MP
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Karmazyn
M
M
Ferrier
G R
GR
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects; D015237:Dinoprost; D011464:Epoprostenol / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000633:toxicity*; D011453:Prostaglandins / Q000502:physiology*; D011460:Prostaglandins F / Q000494:pharmacology; D011863:Radioimmunoassay
D011453:Prostaglandins; D011460:Prostaglandins F; D015121:6-Ketoprostaglandin F1 alpha; D010042:Ouabain; D015237:Dinoprost; D011464:Epoprostenol