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Acute myocardial infarction is triggered by coronary artery occlusion that may be recanalized by thrombolytic therapy with a success rate of up to 75% only. The resistance of coronary artery occlusion to thrombolysis may either be due to obstruction of the lumen by a nonthrombotic mechanism or by intrinsic resistance of thrombus to dissolution. Coronary arterial thrombi are composed of platelet-rich and erythrocyte-rich material in variable proportions. To evaluate the relative sensitivity of these thrombus components to thrombolysis, we have used two femoral arterial thrombosis models in the rabbit, consisting of erythrocyterich clot produced by injecting whole blood and thrombin in an isolated segment and of platelet-rich thrombus spontaneously formed on an everted (inside out) femoral arterial segment. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 30 ,ug/kg/min consistently reperfused arteries occluded with erythrocyte-rich clot (six of six animals compared with zero of six placebo-treated animals, p=0.002), whereas infusion of 30 or 100 ,g/kg/min was significantly less efficient for reperfusion of everted segments occluded with platelet-rich material (only four of 12 animals, p=0.01). Intra-arterial infusion proximal to the occlusion, at a rate of 20 ,ug/kg/min reperfused six of seven rabbits with erythrocyte-rich clots but only one of seven rabbits with occluded everted segments (p=0.03). A dose of 100 ,ug/ kg/min was necessary to reperfuse platelet-rich occlusions in five of six rabbits. We conclude that platelet-rich arterial thrombus is much more resistant to thrombolysis with rt-PA than erythrocyte-rich clot. This differential sensitivity to lysis may explain the failure of thrombolytic therapy in a significant percentage of patients with acute myocardial infarction who may have a predominantly platelet-rich occlusion. The rabbit femoral arterial eversion graft model may represent a useful tool for developing strategies directed at the dissolution of platelet-rich thrombus. (Circulation 1989;79:920-928) Presented in part at the 61st Scientific Meetings of the American Heart Association, Washington, DC, November 14-17, 1988. Supported in part by ISCHEMIA SCOR Grant (HL-25215) and THROMBOSIS SCOR Grant

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