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Research Article Free access | 10.1172/JCI107818

Resolution of Experimental Pulmonary Emboli with Heparin and Streptokinase in Different Dosage Regimens

J. F. Cade, J. Hirsh, E. Regoeczi, M. Gent, M. R. Buchanan, and D. M. Hynes

Department of Pathology, McMaster University, Hamilton, Ontario, Canada

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

Department of Radiology, McMaster University, Hamilton, Ontario, Canada

Find articles by Cade, J. in: PubMed | Google Scholar

Department of Pathology, McMaster University, Hamilton, Ontario, Canada

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

Department of Radiology, McMaster University, Hamilton, Ontario, Canada

Find articles by Hirsh, J. in: PubMed | Google Scholar

Department of Pathology, McMaster University, Hamilton, Ontario, Canada

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

Department of Radiology, McMaster University, Hamilton, Ontario, Canada

Find articles by Regoeczi, E. in: PubMed | Google Scholar

Department of Pathology, McMaster University, Hamilton, Ontario, Canada

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

Department of Radiology, McMaster University, Hamilton, Ontario, Canada

Find articles by Gent, M. in: PubMed | Google Scholar

Department of Pathology, McMaster University, Hamilton, Ontario, Canada

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

Department of Radiology, McMaster University, Hamilton, Ontario, Canada

Find articles by Buchanan, M. in: PubMed | Google Scholar

Department of Pathology, McMaster University, Hamilton, Ontario, Canada

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

Department of Radiology, McMaster University, Hamilton, Ontario, Canada

Find articles by Hynes, D. in: PubMed | Google Scholar

Published October 1, 1974 - More info

Published in Volume 54, Issue 4 on October 1, 1974
J Clin Invest. 1974;54(4):782–791. https://doi.org/10.1172/JCI107818.
© 1974 The American Society for Clinical Investigation
Published October 1, 1974 - Version history
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Abstract

Thrombolytic agents may be useful in acute pulmonary embolism, but their optimal dosage remains uncertain. We have examined the relative efficacy of heparin and different doses of streptokinase, either alone or in combination, in acute experimental pulmonary embolism. A standardized massive embolus of autologous blood clot incorporating canine [125I]-fibrinogen was given to 40 dogs; the degree of resolution after 24 h was quantitated by measuring the radioactivity in the lungs and was compared with detailed postmortem observations.

The amount of residual embolus was 49% in control animals, 28% after heparin (200 U/kg loading dose and 800 U/kg/24 h maintenance dose), and 6% after high dose streptokinase (250,000 U loading dose and 100,000 U/h maintenance dose); it was 31% after low dose streptokinase (25,000 U loading dose and 10,000 U/h maintenance dose), 7% after low dose streptokinase with heparin, 14% after very low dose streptokinase (5,000 U/h without a loading dose) with heparin, and 9% after short course streptokinase (250,000 U loading dose and no maintenance dose) with heparin.

The combination of heparin and low doses or brief courses of streptokinase appeared to be synergistic and produced as much resolution as did standard high dose streptokinase alone. The enhanced resolution of pulmonary emboli in heparin-treated animals may have been due to the prevention by heparin of further deposition of fibrin on the embolus. It appears that dosage regimens of thrombolytic therapy other than those in current use may be worthy of clinical examination.

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