Coronary reflow can be initiated by intravenous 7E3 administration in the presence of heparin and aspirin. In human patients, this flow can be observed in 10 minutes without exogenous thrombolytic agents.

In patients with unstable angina, argatroban inhibits clotting (aPTT prolongation) and thrombin activity toward fibrinogen (fibrinopeptide A decrease), but in vivo thrombin (thrombin-antithrombin III complex) formation is not suppressed. However, cessation of infusion is associated with rebound thrombin (thrombin-antithrombin III complex) generation and with an early dose-related recurrence of unstable angina. Although the mechanism of this clinical and biochemical rebound phenomenon remains to be determined, its implication for the clinical use of specific thrombin inhibitors in the management of ischemic coronary syndromes may be significant.

Twenty-nine patients with acute myocardial infarction were treated with recombinant human tissue-type plasminogen activator (rt-PA). The incidence of acute coronary reocclusion and its prevention by a maintenance infusion of rt-PA were studied. Intravenous rt-PA was given at a rate of 0.4 to 0.75 mg/kg over 60 to 120 min after angiographic documentation of complete coronary occlusion. Reperfusion was accomplished within 1 hr in 24 of 29 patients (83%) and was associated with a decrease of the plasma fibrinogen level by 20%. In a first group of 13 patients, 1 1 of whom were successfully reperfused, prevention of reocclusion was attempted with heparin anticoagulation. However, acute reocclusion within 1 hr after cessation of rt-PA was demonstrated angiographically in five of these patients (45%). Quantitative angiographic analysis indicated that acute reocclusion only occurred in patients with 80% or greater residual stenosis. In patients with less than 80% residual stenosis, heparin anticoagulation was sufficient to maintain patency during the hospital stay in four of five patients. In a second group of patients (n = 16), 13 of whom underwent reperfusion with intravenous rt-PA, seven demonstrated a residual stenosis of 80% or greater. These patients were given heparin and, in addition, 10 mg of rt-PA per hour for 4 hr. None developed acute angiographic reocclusion or clinical signs of reocclusion during the hospital stay. Repeat angiography at 10 to 14 days confirmed persistent patency in six of the seven patients. The maintenance infusion resulted in only a moderate additional drop in fibrinogen, while a steady-state plasma rt-PA level of 750 250 ng/ml was maintained. In five of the six patients with less than 80% residual stenosis maintained on heparin therapy alone, follow-up angiography demonstrated persistent patency. These findings strongly suggest that a maintenance infusion of rt-PA may prevent or greatly reduce the reocclusion rate in patients with 80% or greater residual stenosis after coronary reperfusion with rt-PA. Circulation 73, No. 2, 347-352, 1986. THROMBOLYTIC THERAPY of acute myocardial infarction with streptokinase has often not produced stable coronary patency. The reported in-hospital reocclusion rate after reperfusion with intracoronary streptokinase has ranged from 5% to 29%, with an average of 17%. '61n our investigation of 34 patients with acute myocardial infarction, reocclusion after intracoronary streptokinase was seen in 18% within 2 hr, with an additional 9% of patients experiencing reocclusion before discharge.