Antagonists of PAF and histamine inhibit ouabain-induced cardiac arrhythmias in sensitized guinea-pigs.
Platelet-activating factor (PAF) seems to be involved in different pathophysiological conditions, including cardiac arrhythmia. The arrhythmogenic potency of PAF has been shown experimentally by different methods. PAF antagonists inhibit the PAF-induced enhanced arrhythmogenicity. The present paper demonstrates that the threshold dose of ouabain-induced arrhythmia is decreased in sensitized guinea-pigs. Antagonists of PAF (BN 52021, WEB 2086, WEB 2170) and histamine antagonist clemastine can increase the threshold dose of ouabain-induced arrhythmia. A combination of WEB 2170 and clemastine, each of the drug is a low dose which is without effect when applying one of them only, shows a highly significant antiarrhythmic effect in this method. The threshold dose of ouabain necessary to induce ventricular flutter was increased from 89 micrograms/kg to 129 micrograms/kg and the threshold dose of ventricular fibrillation was enhanced from 101 micrograms/kg to 137 micrograms/kg. In dependence on the pathophysiological conditions, different mediators seem to be involved in the occurrence of cardiac arrhythmia. Therapeutically influencing these mediators could be a real chance to optimise the treatment of such kind of cardiac arrhythmias.
Mest
H J
HJ
Department of Pharmacology and Toxicology, Martin Luther University, Halle, GDR.
Rein
T
T
Riedel
A
A
D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000276:immunology; D001381:Azepines / Q000494:pharmacology; D002974:Clemastine / Q000494:pharmacology; D004224:Diterpenes; D004359:Drug Therapy, Combination; D046934:Ginkgolides; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D007114:Immunization; D007783:Lactones / Q000494:pharmacology; D010042:Ouabain / Q000037:antagonists & inhibitors*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D006633:Histamine Antagonists; D007783:Lactones; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D010042:Ouabain; D002974:Clemastine; C063964:bepafant; C045856:ginkgolide B