This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gold, H. K. Articles by Grossbard, E. Search for Related Content PubMed PubMed Citation Articles by Gold, H. K. Articles by Grossbard, E.

Circulation, Vol 70, 700-707, Copyright © 1984 by American Heart Association

ARTICLES

Coronary thrombolysis with recombinant human tissue-type plasminogen activator

HK Gold, JT Fallon, T Yasuda, RC Leinbach, BA Khaw, JB Newell, JL Guerrero, FM Vislosky, CF Hoyng and E Grossbard

The thrombolytic potency and myocardial infarct--sparing potential of recombinant tissue-type plasminogen activator (rt-PA) were studied in electrocardiographically monitored, open-chest, anesthetized dogs. Localized coronary thrombosis was produced in the left anterior descending artery by endothelial injury and instillation of thrombin and fresh blood. After 2 hr of stable thrombotic occlusion, rt-PA was infused intravenously. At a dose of 4.3 micrograms/kg/min, time to reperfusion was greater than 40 min (n = 3). However, at higher infusion rates a linear, dose-dependent time to coronary reperfusion was obtained (r = .88): at 10 micrograms/kg/min reperfusion occurred after 31 +/- 2 min (n = 3), at 15 micrograms/kg/min it was at 26 +/- 7 min (n = 4), and at 25 micrograms/kg/min, lysis was accomplished within 13 +/- 3 min (n = 3). Thrombolysis was not associated with alterations in either plasma hemostatic factors (fibrinogen, plasminogen, and alpha 2-antiplasmin) or in systemic blood pressures. Epicardial electrographic measurements revealed a significant reduction in ST elevation in all reperfused hearts. A randomized, blinded study was also carried out with 15 micrograms/kg/min of rt-PA saline in 18 dogs with 30 min of coronary thrombosis. Reperfusion in the treated group occurred after 28 +/- 3 min. No evidence of thrombolysis was noted in the saline-treated group within 240 min. Size of myocardial infarction was determined by triphenyl tetrazolium chloride staining and planimetry. Infarction involved 2.5 +/- 0.5% of the left ventricular wall in the group receiving rt-PA, but 16 +/- 3% of the left ventricle in the saline-treated group (p = .001). It is concluded that intravenous infusion of rt-PA results in rapid, dose-dependent coronary thrombolysis without systemic fibrinolytic activation and that early lysis of coronary thrombi is associated with substantial salvage of myocardial tissue.

This article has been cited by other articles:

				D. Collen Fibrin-Selective Thrombolytic Therapy for Acute Myocardial Infarction Circulation, March 1, 1996; 93(5): 857 - 865. [Full Text]