Encapsulation of a plasminogen activator speeds reperfusion, lessens infarct and reduces blood loss in a canine model of coronary artery thrombosis

J. Kent Leach; Eugene Patterson; Edgar A. O’Rear

doi:10.1160/TH03-11-0704

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(06): 1213-1218
DOI: 10.1160/TH03-11-0704

Cell Signaling and Vessel Remodeling

Schattauer GmbH

Encapsulation of a plasminogen activator speeds reperfusion, lessens infarct and reduces blood loss in a canine model of coronary artery thrombosis

J. Kent Leach

¹School of Chemical Engineering and Materials Science, University of Oklahoma, Norman, Oklahoma, USA

²University of Oklahoma Bioengineering Center, Norman, Oklahoma, USA

,

Eugene Patterson

³University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA

,

Edgar A. O’Rear

¹School of Chemical Engineering and Materials Science, University of Oklahoma, Norman, Oklahoma, USA

²University of Oklahoma Bioengineering Center, Norman, Oklahoma, USA

› Author Affiliations

Abstract

Summary

In the present study, a polymer-encapsulated plasminogen activator was investigated as an alternative to restore blood flow more effectively than free plasminogen activator. While current fibrinolytic agents have limited efficacy, attributable to delayed onset of sustained reperfusion and bleeding complications, encapsulated plasminogen activators have shown promise in addressing these shortcomings. A polymer-encapsulated plasminogen activator could offer an effective formulation with a prolonged shelf-life. In this study, coronary artery thrombosis was produced in the anesthetized dog by the injection of thrombin + whole blood, and then one of five randomly selected formulations was administered intravenously: saline, blank microcapsules, free streptokinase (FREE SK), streptokinase and blank microcapsules (FREE SK + BLANK), or streptokinase entrapped in polymer microcapsules (MESK). MESK significantly accelerated the time to reperfusion compared to FREE SK or FREE SK + BLANK. Additionally, substantial reductions were observed in residual clot mass, infarct mass, reocclusion episodes, fibrinogen depletion and blood loss with MESK compared to FREE SK. The results of this study demonstrate that MESK accelerates thrombolysis and the restoration of blood flow compared to identical dosages of FREE SK while also reducing systemic fibrinogenolysis and blood loss. Microencapsulation may produce an improved dosage form for restoring arterial blood flow and reducing bleeding complications with thrombolytic therapy.

Keywords

Plasminogen activators - thrombolytic agents - fibrinogen/fibrin

Full Text

References

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