Ultrasound affects distribution of plasminogen and tissuetype plasminogen activator in whole blood clots in vitro

Branka Devcic-Kuhar; Stefan Pfaffenberger; Lisa Gherardini; Christoph Mayer; Martin Gröschl; Christoph Kaun; Ewald Benes; Erwin Tschachler; Kurt Huber; Gerald Maurer; Johann Wojta; Michael Gottsauner-Wolf

doi:10.1160/TH04-02-0119

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(05): 980-985
DOI: 10.1160/TH04-02-0119

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Ultrasound affects distribution of plasminogen and tissuetype plasminogen activator in whole blood clots in vitro

Branka Devcic-Kuhar^*

¹Institute of General Physics, Vienna University of Technology, Austria

,

Stefan Pfaffenberger^*

²Department of Internal Medicine II, University of Vienna, Austria

,

Lisa Gherardini

³Department of Pharmacology, Conway Institute, University College Dublin, Ireland

,

Christoph Mayer

⁴Department of Dermatology, University of Vienna, Austria

,

Martin Gröschl

¹Institute of General Physics, Vienna University of Technology, Austria

,

Christoph Kaun

²Department of Internal Medicine II, University of Vienna, Austria

,

Ewald Benes

¹Institute of General Physics, Vienna University of Technology, Austria

,

Erwin Tschachler

⁴Department of Dermatology, University of Vienna, Austria

,

Kurt Huber

²Department of Internal Medicine II, University of Vienna, Austria

,

Gerald Maurer

²Department of Internal Medicine II, University of Vienna, Austria

,

Johann Wojta^‡

²Department of Internal Medicine II, University of Vienna, Austria

,

Michael Gottsauner-Wolf^‡

²Department of Internal Medicine II, University of Vienna, Austria

› Author Affiliations

Abstract

Summary

Ultrasound of 2 MHz frequency and 1.2 W/cm2 acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% ± 6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% ± 4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 ± 2513 ng/ml vs. 2364 ± 725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 ± 2.6 µm to 21.2 ± 7.2 µm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.

Keywords

Thrombolysis - ultrasound - sonothrombolysis - immunohistochemistry - fibrinolytic enzymes

Full Text

References

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