Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium.
We examined the effect of coronary thrombolysis by recombinant tissue-plasminogen activator (rtPA) on infarct size using a thrombin-induced thrombosis model of open-chest anesthetized dog. Occlusive thrombus was induced by injection of thrombin (100 U) in the left anterior descending coronary artery (LAD). The intravenous infusion of rtPA (10 micrograms/kg/min) was started at 30 min (30 min-ischemia group) or at 60 min (60 min-ischemia group) after the formation of thrombus, and was continued for 30 min. Spontaneous thrombolysis was not observed in the 360 min-ischemia (vehicle-treated) group. Intravenous infusion of rtPA elicited thrombolysis within 30 min in all the dogs except in one in the 60 min-ischemia group. The infarct size was significantly reduced by rtPA-induced thrombolysis. The shorter the duration of the ischemia, the longer the effect of the drug, and the infarct size after thrombolysis was smaller in the 30 min-ischemia group than in the 60 min-ischemia group. Ischemia-induced changes in ST-segment of electrocardiogram (ECG) were significantly ameliorated after thrombolysis in both 60 min- and 30 min-ischemia group. These results suggest that early reperfusion of coronary thrombosis by rtPA is beneficial to the ischemic myocardium.
Higo
K
K
Department of Pharmacology, Kyowa Hakko Kogyo Co., Shizuoka, Japan.
Karasawa
A
A
Kubo
K
K
D000758:Anesthesia; D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy*; D003328:Coronary Thrombosis / Q000097:blood / Q000188:drug therapy; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator