Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog.
Platelet activation and aggregation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Molsidomine (M), isosorbide dinitrate (ISDN) and nitroglycerin (NTG) have been found to inhibit platelet aggregation in vitro. In the present study, the activity of these compounds was investigated in a model of coronary artery thrombosis in vivo. Dogs were anesthetized, thoracotomized, and their heart was exposed. An electrode was inserted into the left circumflex coronary artery and set to rest on the intima. Electrical stimulation (9 V, 150 microA) lasted for 6 h. Compounds (each in 2 dose levels) were given as an i.v. infusion starting 30 min after the beginning of the stimulation and lasting for the duration of the experiment. All control (saline-treated) animals underwent thrombotic occlusion of the coronary artery as assessed by flow measurement. On the other hand, 2/8 dogs treated with the lower M dose and 4/8 dogs treated with the higher M dose did not have a coronary occlusion. Neither ISDN nor NTG, at both doses, prevented the coronary occlusion. In control animals thrombus wet weight was 74.43 +/- 11.25 mg. M reduced the thrombus weight in a dose-related manner, while ISDN (marginally) and NTG (significantly at the higher dose) increased this parameter. Following the coronary thrombosis, all control animals developed myocardial infarcts as assessed by the tetrazolium technique. Similarly all animals treated with ISDN and with NTG (at both doses) showed infarcts. However, 3/8 M-dogs did not have a myocardial infarction in the lower as well as in the higher dose groups. The hemodynamic changes induced by the 3 compounds were similar in magnitude. Thus M but not ISDN or NTG showed in this in-vivo study antithrombotic and consequently antiischemic activity.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D008981:Molsidomine; D009203:Myocardial Infarction / Q000188:drug therapy; D005996:Nitroglycerin / Q000627:therapeutic use*; D010069:Oxadiazoles / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D013558:Sydnones / Q000627:therapeutic use*
D010069:Oxadiazoles; D013558:Sydnones; D008981:Molsidomine; D005996:Nitroglycerin; D007548:Isosorbide Dinitrate