A Novel Modified t-PA, E-6010, Induces Faster Recovery of Ventricular Function after Coronary Thrombolysis than Native t-PA in a Canine Thrombosis Model

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Using the centerline method in a canine model, we compared left ventricular function after coronary thrombolysis induced by a novel modified recombinant tissue plasminogen activator (rt-PA) (E6010: ^<84>Cys→^<84>Ser) to that induced by rt-PA or urokinase. Thirty minutes after occlusion, a bolus injection of E6010 (0.2mg/kg) or a continuous infusion of either rt-PA (0.6mg/kg over 1h) or urokinase (0.38 mg/kg over 1h) was administered intravenously. Animals with sustained copper coil-occlusion served as non-reperfused controls. Left ventricular ejection fraction and regional wall motion (expressed as the infarction chord number; ie, the number of chords < -2SD among chords 12-66) were 42±5%^<**> and 5±3^<**> respectively, in the E6010 group, 31±8% and 16±12 in the rt-PA group, and 31±2% and 32±13 in the urokinase group 1h after reperfusion, indicating earlier recovery of left ventricular function after thrombolysis in the E6010 group than in the rt-PA and urokinase groups (^<**>p<0.01 vs control). Coronary reperfusion with E6010 induced earlier recovery of left ventricular function than reperfusion with rt-PA or urokinase. These results suggest that E6010 may be of clinical value in the treatment of coronary occlusion.
社団法人日本循環器学会の論文
1995-03-20