The activity of molsidomine in experimental models of ischemic cardiac disease.
The cardioprotective and antithrombotic activity of molsidomine, a novel therapeutic agent for the treatment of coronary heart disease, was investigated in a series of animal models of myocardial ischemia. Molsidomine given to dogs with marked ST segment elevation (epicardial electrogram), induced by a reduction of left descending coronary artery (LAD) flow to 20% to 30% of the original value, resulted within 40 minutes in complete normalization of ECG changes. In another animal model molsidomine given either before or after occlusion of the LAD significantly reduced infarct size. All these molsidomine effects were accompanied by a marked lowering of preload, resulting in a reduction of extravascular coronary artery resistance and in increased blood flow toward the ischemic zones. In a model of myocardial ischemia and reperfusion in the anesthetized dog, molsidomine had a marked protective effect against the incidence of spontaneous ventricular fibrillation. This effect could also be attributed to the anti-ischemic activity of molsidomine, which would reduce the disparity between the refractory periods in normal and ischemic areas and thus increase ventricular stability. The antithrombotic activity of molsidomine was investigated in dogs in which the left circumflex coronary artery was electrically stimulated, a procedure that leads to thrombotic occlusion. Molsidomine in a dose-dependent manner prevented coronary thrombotic occlusion and reduced thrombus wet weight and the size of the resulting infarction. These effects of molsidomine were not related to its hemodynamic activity, since nitroglycerin and isosorbide dinitrate had similar hemodynamic effects but did not prevent coronary thrombosis. The antithrombotic activity of molsidomine is probably related to its ability to lower coronary venous blood thromboxane levels.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D008981:Molsidomine; D005996:Nitroglycerin / Q000627:therapeutic use; D010069:Oxadiazoles / Q000627:therapeutic use*; D013558:Sydnones / Q000494:pharmacology / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000097:blood; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control
D010069:Oxadiazoles; D013558:Sydnones; D014665:Vasodilator Agents; D013929:Thromboxane B2; D008981:Molsidomine; D005996:Nitroglycerin