Effect of molsidomine on thrombus formation in stenosed coronary arteries of dogs and pigs.
The purpose of the present study was to examine the effect of molsidomine in stenosed coronary arteries of anesthetized dogs and pigs. Stenosis and vascular damage resulted in cyclical reductions of coronary blood flow due to periodic acute platelet thrombus formation in the narrowed lumen. Cyclical flow reductions were quantitated by their frequency and severity. In adult dogs with critical stenosis, molsidomine reduced significantly both the frequency and severity of the cyclical reductions in the first hour following injection, whereas both parameters remained constant in control dogs. Aspirin also significantly reduced the frequency and severity of flow reductions. In young dogs, cyclical flow reductions developed only when epinephrine was added to the combination of critical stenosis plus endothelial damage. In this model, molsidomine reduced the severity of flow reductions but not their frequency. Aspirin reduced both parameters. In young pigs, cyclical flow reductions were induced by subcritical stenosis. Molsidomine reduced the severity but not significantly the frequency of the cyclical flow reductions. A higher dose of molsidomine abolished them in three additional pigs; this effect was reversed by a subsequent injection of hemoglobin. It is concluded that molsidomine, like aspirin, possesses antithrombotic activity. This effect may entirely or in part, be due to the release of nitric oxide.
Just
M
M
Department of Pharmacology, Cassella AG, Frankfurt/Main, F.R.G.
Martorana
P A
PA
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage; D003326:Coronary Circulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000503:physiopathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D013552:Swine
D008981:Molsidomine; D001241:Aspirin