Abstract
We sought to examine to what extent a combination of strong thromboxane A2 synthase inhibition and moderate endoperoxide receptor blockade enhances streptokinase-induced coronary thrombolysis and provides anti-ischemic activity independent from its thrombolytic activity. Coronary thrombi, induced by crush injury and stenosis of the coronary artery, were lysed with streptokinase, 10,000 IU/kg body weight over 90 min, in anesthetized dogs receiving solvent (n = 11), ridogrel, 0.31 mg/kg intravenously, for thromboxane A2 synthase inhibition (n = 7) or ridogrel, 5 mg/kg, for additional prostaglandin endoperoxide receptor antagonism in addition to thromboxane A2 synthase inhibition (n = 7) 10 min before the administration of streptokinase. Thrombolytic efficacy was greatest in animals receiving both dual-acting ridogrel, 5 mg/kg intravenously, and streptokinase as evidenced by the highest incidence of high grade coronary reperfusion (solvent 3 of 11; ridogrel, 0.31 mg/kg, 5 of 7; ridogrel, 5 mg/kg, 7 of 7; p < 0.05 vs. solvent) within the shortest delay (solvent 210 min; ridogrel, 0.31 mg/kg, 85 min; ridogrel, 5 mg/kg, 37 min; p < 0.05 vs. solvent and ridogrel, 0.31 mg/kg) and the lowest incidence of reocclusion (solvent 5 of 7; rid...Continue Reading
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