Coronary thrombolysis with recombinant human tissue-type plasminogen activator.

Abstract

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.

• Authors: H K Gold, J T Fallon, T Yasuda, R C Leinbach, B A Khaw, J B Newell, J L Guerrero, F M Vislosky, C F Hoyng, E Grossbard
• Journal: Circulation (Circulation) Vol. 70 Issue 4 Pg. 700-7 (Oct 1984) ISSN: 0009-7322 [Print] United States
• PMID: 6541103 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• alpha-2-Antiplasmin
• Fibrinogen
• Plasminogen
• Plasminogen Activators

Topics

• Animals
• Coronary Angiography
• Coronary Disease (diagnostic imaging, drug therapy)
• Disease Models, Animal
• Dogs
• Dose-Response Relationship, Drug
• Electrocardiography
• Fibrinogen (metabolism)
• Fibrinolysis (drug effects)
• Myocardial Infarction (diagnostic imaging, drug therapy)
• Plasminogen (metabolism)
• Plasminogen Activators (therapeutic use)
• alpha-2-Antiplasmin (metabolism)