Reduction of occlusive coronary artery thrombosis and myocardial ischemia by molsidomine in anesthetized dogs.
The antianginal drug molsidomine was evaluated for its in vivo antithrombotic effects in barbiturate-anesthetized open-chest dogs by inducing left circumflex (LCX) coronary artery thrombosis with low-amperage stimulation (150 microA for 6 h) of the intimal surface of the vessel. Intravenous bolus administration of 0.10 mg/kg molsidomine 10 min prior to onset of electrical stimulation partially prevented occlusive LCX thrombosis and prolonged time to complete vessel occlusion by 45 min (p less than 0.05). Intracoronary thrombus mass was reduced (14 +/- 0.8 vs. 32 +/- 4 mg in controls, p less than 0.05). Final 6-h infarcts after complete LCX coronary artery thrombosis were measured by triphenyltetrazolium chloride (TTC) staining and were smaller after molsidomine pretreatment when related to left ventricular mass (14 +/- 3 vs. 28 +/- 2%, p less than 0.02) or to the LCX vessel area at risk for infarction (18 +/- 3 vs. 58 +/- 4%, p less than 0.01). Molsidomine did not induce hemodynamic alterations during time to complete thrombotic LCX coronary artery occlusion. In saline controls, heart rate and end-diastolic pressure increased whereas blood pressure and contractility decreased significantly. The percentage of ventricular ectopic beats concomitant to thrombus formation and myocardial ischemia was significantly reduced in the drug-treated dogs. Molsidomine also partially prevented the reduction in myocardial function parallel to blood flow diminution as measured with an ultrasonic technique. The drug further exerted significant ex vivo inhibition of collagen-induced platelet aggregation (p less than 0.01 vs. control from 4 h after onset of LCX stimulation). In addition to established hemodynamic effects of molsidomine there may also be a direct effect on platelet aggregation and thrombus formation in vivo which delays coronary artery narrowing and occlusion as one primary cause for myocardial ischemia.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008981:Molsidomine; D010069:Oxadiazoles / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D013558:Sydnones / Q000627:therapeutic use*
D010069:Oxadiazoles; D013558:Sydnones; D008981:Molsidomine