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.
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: 84Cys-->84Ser) to that induced by rt-PA or urokinase. Thirty minutes after occlusion, a bolus injection of E6010 (0.2 mg/kg) or a continuous infusion of either rt-PA (0.6 mg/kg over 1 h) or urokinase (0.38 mg/kg over 1 h) 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 1 h 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.
Suzuki
S
S
Tsukuba Research Laboratories, Eisai Co., Ltd, Ibaraki, Japan.
Saito
M
M
Yui
Y
Y
Kawai
C
C
D000818:Animals; D003328:Coronary Thrombosis / Q000188:drug therapy*; D006224:Cricetinae; D004195:Disease Models, Animal; D004285:Dogs; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006331:Heart Diseases; D008297:Male; D008647:Mesocricetus; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D015424:Reperfusion; D013318:Stroke Volume; D013995:Time; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*
D011993:Recombinant Fusion Proteins; C076356:E 6010; D004815:Epidermal Growth Factor; D010959:Tissue Plasminogen Activator