Effect of sulfinpyrazone on ventricular arrhythmia, prostaglandin synthesis, and catecholamine release following coronary artery occlusion in the cat.
We examined if inhibition of endogenous prostaglandin (PG) synthesis reduced the severity of ventricular arrhythmia and the incidence of ventricular fibrillation (VF) following occlusion of the left anterior descending coronary artery (LAD) in anesthetized cats. We also determined whether the PGs were interacting in a facilitory manner with the sympathetic nervous system to produce arrhythmia and VF after LAD occlusion. Sulfinpyrazone, an inhibitor of cyclo-oxygenase enzyme, or vehicle was administered intravenously to cats 1 h before LAD occlusion. Sulfinpyrazone completely (p less than 0.001) inhibited the release of 6-keto-PGF1 alpha into the great cardiac vein following LAD occlusion. Sulfinpyrazone (100 mg/kg) significantly (p less than 0.001) reduced the amount of ventricular arrhythmia and the incidence of VF (p less than 0.05) in the 1st h after LAD occlusion. In addition to 6-keto-PGF1 alpha sulfinpyrazone also (p less than 0.001) inhibited the increase in plasma norepinephrine from the heart due to sympathetic nervous system stimulation following LAD occlusion. Since sulfinpyrazone was ineffective in increasing the dose of digoxin required to produce arrhythmia and death, sulfinpyrazone apparently did not depress cardiac excitability. Finally, the extent of infarction resulting from LAD occlusion was not different in sulfinpyrazone-treated animals compared with control. These data indicate that sulfinpyrazone, by inhibiting endogenous PG synthesis in the heart following LAD occlusion, may prevent a facilitory interaction between PGs and the sympathetic nervous system that contributes, in part, to the development of ventricular arrhythmia and VF normally associated with this event.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D002395:Catecholamines / Q000097:blood*; D002415:Cats; D003327:Coronary Disease / Q000150:complications* / Q000378:metabolism; D003645:Death, Sudden / Q000517:prevention & control; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011453:Prostaglandins / Q000096:biosynthesis*; D013442:Sulfinpyrazone / Q000494:pharmacology*
D002395:Catecholamines; D011453:Prostaglandins; D013442:Sulfinpyrazone; D009638:Norepinephrine