Effect of prostaglandin synthesis inhibition and sympathectomy on ouabain-induced arrhythmia in cats.
The purpose of this study was to examine the importance of endogenous prostaglandins (PGs) and sympathectomy on the arrhythmogenic action of ouabain. Cats, anesthetized with dial-urethane, were infused intravenously with ouabain continuously. The dose of ouabain necessary to produce arrhythmia (AR), ventricular tachycardia (VT), and death was determined. Pretreatment with sulfinpyrazone at 100 mg kg-1 i.v. 1 h before glycoside infusion was used to inhibit PG synthesis. Removal of endogenous PGs  with sulfinpyrazone reduced the cardiotoxic dose of ouabain. Sympathetic influences were removed by: (a) destroying sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA); (b) depleting nerve terminal catecholamines with reserpine; or (c) preventing catecholamine release from the nerve terminal  with bretylium. Reduction of sympathetic influences with reserpine or bretylium increased the cardiotoxic dose of ouabain; whereas removal of nerve terminals with 6-OHDA did not alter the toxic dose of ouabain from that found in control animals. When endogenous PG synthesis was inhibited with sulfinpyrazone the protective effects of reserpine and bretylium were eliminated. These results suggest that endogenous PGs protect against the arrhythmogenic action of ouabain, not only by interfering with catecholamine influences at the sympathetic nerve terminal, but also by a mechanism independent of sympathetic inhibition. Furthermore, the protective action of agents which diminishes the cardiotoxic action of ouabain by interfering with sympathetic influences is lost when endogenous PGs are removed. Finally, 6-OHDA, which destroys the sympathetic nerve terminals, removes both the arrhythmic influence of the catecholamine as well as the protective influence of the PG, resulting in no net change in the cardiotoxic dose of this glycoside.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000633:toxicity*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D013442:Sulfinpyrazone / Q000494:pharmacology; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects*
D002395:Catecholamines; D006892:Hydroxydopamines; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D010042:Ouabain; D013442:Sulfinpyrazone