Evaluation of thrombolytic and systemic effects of the novel recombinant plasminogen activator BM 06.022 compared with alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis

Department of Pharmacology, Boehringer Mannheim GmbH, Germany.

The thrombolytic and systemic effects of BM 06.022 were evaluated and compared with those of alteplase, anistreplase, streptokinase and urokinase in a canine model of coronary artery thrombosis. BM 06.022 consists of the kringle-2 and protease domains of human tissue plasminogen activator (t-PA) and is unglycosylated because of its expression in Escherichia coli cells. Thrombus formation in anesthetized open chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery at a high level site of obstruction. In heparinized dogs, none of six vehicle-treated animals exhibited reperfusion. Reperfusion was achieved in four of six dogs at 18.3 +/- 6 min after intravenous bolus injection of 140 kU/kg (0.24 mg/kg) of BM 06.022, whereas four of six dogs exhibited reperfusion later (p less than 0.05) at 76.5 +/- 16.1 min during infusion of 1.33 mg/kg of alteplase (0.13 mg/kg as initial bolus injection, followed by 0.66 mg/kg over 1 h and 0.53 mg/kg over 2 h). Significantly later (p less than 0.05) reperfusion than that achieved with BM 06.022 was achieved in five of six dogs at 57.8 +/- 12.1 min after intravenous injection of 0.4 U/kg of anistreplase. Streptokinase (21,000 IU/kg over 60 min) and urokinase (20,000 IU/kg as an intravenous bolus injection, followed by 20,000 IU/kg over 89 min) each induced reperfusion in three of six dogs but at 67 +/- 12 and 84.3 +/- 17.1 min (p less than 0.05 vs. BM 06.022), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				R. L White Thrombolytic Therapy in Acute Myocardial Infarction Part II: 1997 Update Asian Cardiovasc Thorac Ann, March 1, 1998; 6(1): 03 - 10. [Abstract] [Full Text] [PDF]

				C. Bode, R. W. Smalling, G. Berg, C. Burnett, G. Lorch, J. M. Kalbfleisch, R. Chernoff, L. G. Christie, R. L. Feldman, A. A. Seals, et al. Randomized Comparison of Coronary Thrombolysis Achieved With Double-Bolus Reteplase (Recombinant Plasminogen Activator) and Front-Loaded, Accelerated Alteplase (Recombinant Tissue Plasminogen Activator) in Patients With Acute Myocardial Infarction Circulation, September 1, 1996; 94(5): 891 - 898. [Abstract] [Full Text]

				R. W. Smalling, C. Bode, J. Kalbfleisch, S. Sen, P. Limbourg, F. Forycki, G. Habib, R. Feldman, S. Hohnloser, and A. Seals More Rapid, Complete, and Stable Coronary Thrombolysis With Bolus Administration of Reteplase Compared With Alteplase Infusion in Acute Myocardial Infarction Circulation, June 1, 1995; 91(11): 2725 - 2732. [Abstract] [Full Text]