Protective effects of dazmegrel on the PAF potential of ouabain-induced cardiac arrhythmias.
The ouabain threshold to induce cardiac arrhythmias in urethane-anaesthetized guinea-pigs was not modified by the administration of either dazmegrel, 4 mg/kg i.v., or lysine-acetylsalicylate, 13.5 mg/kg i.v., 5 min before the infusion of ouabain,10g/kg per min i.v. The previous administration of platelet-activating factor (PAF), 0.01 to 1 nmol/animal i.v., 2 min prior to ouabain, caused a significant, dose-dependent decrease of the ouabain threshold for the cardiac rhythm disturbances. Lysine-acetylsalicylate lacked any effect on this PAF potentiation. Pretreatment with dazmegrel 5 min before PAF, 0.05 nmol/animal i.v., abolished the PAF potentiation of the digitalis-induced arrhythmias. These results suggest that thromboxane synthesis is involved in this PAF effect and indicate an ability of PAF to induce thromboxane generation even in the case of cyclooxygenase inhibition.
Salinas
P
P
Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain.
Barrigón
S
S
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000517:prevention & control*; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000627:therapeutic use*; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D010042:Ouabain; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology
D007093:Imidazoles; D010972:Platelet Activating Factor; C039242:dazmegrel; D010042:Ouabain; D013930:Thromboxane-A Synthase; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate