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

The effects of bolus injections of recombinant single-chain tissue-type plasminogen activator (rt-PA) and of F(ab')2 fragments of a murine monoclonal antibody (7E3) Bleeding times remained unchanged after injection of rt-PA alone and were moderately (about twofold) prolonged after the injection of 7E3-F(ab')2 at a dose of 0.1 to 0.4 mg/kg. With 0.6 mg/kg 7E3-F(ab')2 the bleeding time prolonged approximately four times and was greater than 30 min in four of nine dogs. At 0.8 mg/kg the bleeding time was consistently prolonged to more than 30 min; this dose blocked 83 -+ 5% of the GPIIb/IIIa receptors on the platelet surface. Thus, injection of F(ab')2 fragments of the monoclonal antibody 7E3, directed against the platelet GPIIb/IIIa receptor, accelerates thrombolysis with rt-PA and prevents reocclusion. Antagonists of the platelet GPIIb/IIIa receptor may constitute useful adjunctive therapy for coronary arterial thrombolysis in patients with acute myocardial infarction.

The effect of heparin and of the synthetic competitive thrombin inhibitor (2R,4R)-4-methyl-1-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfon yl)-L-arginyl]-2-piperidinecarboxylic acid monohydrate (argatroban) on platelet-rich arterial thrombosis was studied in a rabbit model, consisting of a 4-6-mm everted ("inside-out") femoral arterial segment. Intravenous injection of heparin (200 units/kg) failed to prevent occlusion within 60 minutes in all 10 rabbits, whereas intravenous argatroban infusion at a rate of 100 or 200 micrograms/kg/min for 60 minutes, which prolonged the thrombin time more than fourfold, prevented thrombosis in nine of 13 rabbits (p = 0.002 vs. i.v. heparin). Intra-arterial infusion of 200 units/kg heparin over 60 minutes prevented occlusion in six of nine rabbits (p = 0.003 vs. i.v. heparin), whereas intra-arterial argatroban at a rate of 100 micrograms/kg/min for 60 minutes prevented thrombosis in all 10 rabbits (p = 0.00001 vs. i.v. heparin). Patency of femoral arterial segments was maintained after the end of the intra-arterial heparin and intravenous or intra-arterial argatroban infusion for up to 3 hours despite normalization of the thrombin time and partial thromboplastin time. Pathologic examination of the graft revealed that the inverted adventitial surface was covered by layers of platelets without platelet aggregation or fibrin deposition. These findings indicate that thrombin plays an important role in platelet-rich arterial thrombosis, and that the thrombogenic stimulus is rapidly attenuated by short-term infusion of the synthetic thrombin inhibitor. Selective thrombin inhibition can constitute an alternative approach to the prevention of arterial occlusion after angioplasty or thrombolytic therapy in patients with unstable coronary syndromes.

Percutaneous balloon pericardiotomy is successful in helping to manage large pericardial effusions, particularly in patients with a malignant condition. It may become the preferred treatment to avoid a more invasive procedure for patients with pericardial effusion and a limited life expectancy.

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We performed percutaneous balloon pericardial window (PBPW) in 8 patients (age 40 to 70 yrs; 4 men, 4 women) with malignant pericardial effusion and tamponade. Pericardial window was indicated because they continued to drain greater than 100 ml/day of pericardial fluid through the pigtail catheter for greater than or equal to 3 days. A 0.038 inch guidewire was advanced through the pigtail catheter into the pericardial space and then the catheter was removed. A 20 mm diameter, 3 cm long balloon dilating catheter was advanced to straddle the parietal pericardium. Manual inflations were performed until the waist produced by the pericardium disappeared. All patients tolerated the procedure well with minimal discomfort and with no complications. A left or bilateral pleural effusion occurred in all patients after PBPW. No patient developed recurrent pericardial tamponade at a mean follow-up of 6 +/- 2 months. Thus, PBPW is a useful and safe technique to avoid surgery in patients with malignant pericardial effusion and tamponade.

The purpose of this study was to correlate bleeding complications during and after treatment with recombinant tissue-type plasminogen activator (rt-PA)