The effects of oral nafazatrom (= BAY g 6575) on canine coronary artery thrombosis and myocardial ischemia.

The in-vivo effects of the new antithrombotic compound nafazatrom on experimental thrombosis of the left circumflex coronary artery, on hemodynamics and on ultimate infarct size were studied in pentobarbital-anesthetized, open-chest dogs. Coronary artery thrombosis was induced by low amperage stimulation (150 microA, DC for 6 hr) of the circumflex artery intimal lining. The effects of oral pretreatment of 1%-Tylose suspension as drug diluent and 5 mg/kg nafazatrom plus vehicle were determined. Both agents were administered twice a day before onset of current stimulation. In the drug vehicle group, coronary thrombosis caused severe hemodynamic alterations, e.g. blood pressure and left ventricular pressure decrease, as well as reduction in the LV dP/dtmax associated with increases in end-diastolic filling pressure and heart rate. Time to coronary artery occlusion was delayed by nafazatrom (5.2 +/- 1.1 vs 3.1 +/- 0.4 hr, p less than 0.05). Smaller blood pressure and LV dP/dtmax reductions and minor heart rate and filling pressure increases around the time of thrombus formation suggested cardioprotection with the drug. Smaller R wave changes and S-T segment elevation indicated minor ischemia at the time of occlusive coronary artery occlusion in nafazatrom-treated hearts (24 +/- 0.5 vs 72 +/- 7% ST segment elevation, p less than 0.01). Thrombus wet weight was 18.4 +/- 2.6 mg in the nafazatrom group, but 63.7 +/- 3.1 mg in controls (p less than 0.01). Thus, ultimate infarct size was smaller in nafazatrom-treated hearts as related to left ventricular mass (8.4 +/- 1.4 vs 32.3 +/- 3.1%, p less than 0.02) or to the occluded artery perfusion area at risk for infarction (16 +/- 3.4 vs 53 +/- 6.2%, p less than 0.05). No ex-vivo effect of nafazatrom on collagen-induced platelet aggregation was observed. These results may indicate efficacy of the drug in prevention of acute coronary artery disease as one cause of ischemic jeopardy of the myocardium and/or therapeutic value in coronary artery spasm.