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.

Forty-three patients (mean age 62 +/- 1 years) were treated for ventricular septal defect (VSD) secondary to myocardial infarction. Whenever possible, operation was postponed until six weeks post-onset chest pain. However, hemodynamic instability, evidenced by cardiogenic shock, refractory pulmonary edema, or a rising blood urea nitrogen (BUN) forced operation in 21 patients within 21 days post-infarct (Group I). In seven patients operation was performed three to six weeks post-infarct (Group II). In only eight patients could operation be delayed beyond six weeks post-infarct (Group III). Clinical deterioration, once begun, progressed rapidly, and could be reversed only temporarily by intra-aortic balloon pumping, used in 26 patients for safe conduct of cardiac catheterization and for peri-operative hemodynamic support. Hospital survival was achieved in 24 of the 36 operated patients (66%). In Group I patients, ten of 21 survived. In Group II, six of seven survived. In Group III, eight of eight patients survived. There have been five late deaths with a mean follow-up of 41 months in survivors. Improved survival has been achieved recently by the greater use of prosthetic material to replace necrotic muscle and by a transinfarct incision regardless of infarct location. Operative mortality before 1973 was 47%; mortality after 1973 was only 18%, with a concomitant reduction of mortality (30%) even in Group I patients.

SUMMARY Forty-one patients with postinfarction ventricular septal rupture were cared for in our hospital during [1971][1972][1973][1974][1975]. Cardiogenic shock developed after septal rupture in 55% of these patients. Shock was unrelated to site of infarction, extent of coronary artery disease, left ventricular ejection fraction, or pulmonaryto-systemic flow ratio, but mean pulmonary artery pressure was lower in shock than in nonshock patients. These observations suggest that shock was produced mainly by right ventricular impairment. Perioperative ventriculography, three had undergone coronary angiography alone, and two had undergone left ventriculography alone.The diagnosis of ventricular septal rupture was established by a right atrial-to-pulmonary artery step-up in oxygen content in 38 patients. The pulmonary-tosystemic flow ratio was calculated using a standard formula."We define cardiogenic shock as systemic hypotension (mean arterial blood pressure < 70 mm Hg) accompanied by either oliguria (urine output < 20 ml/hr for 4 hours or more) or a rising blood urea nitrogen (to > 50 mg/dl).The