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Thromb Haemost 1997; 78(03): 1063-1068
DOI: 10.1055/s-0038-1657688
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Ultrasound Reversibly Disaggregates Fibrin Fibers

Julie V Braaten
The Vascular Medicine Unit, Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA
,
Rachel A Goss
The Vascular Medicine Unit, Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA
,
Charles W Francis
The Vascular Medicine Unit, Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, NY, USA
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Publikationsverlauf

Received 27. 1997

Accepted after revision 12. Mai 1997

Publikationsdatum:
12. Juli 2018 (online)

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Summary

Ultrasound accelerates fibrinolysis in vitro and in vivo, primarily through non-thermal mechanisms including cavitation. We have previously observed that ultrasound reversibly increases flow through fibrin gels, a property primarily determined by the structure of the fibrin matrix. Therefore, the effect of ultrasound on the ultrastructure of fibrin gels was examined using scanning electron microscopy. Non-cross- linked fibrin gels were fixed and prepared for microscopy before, during and after exposure to 1 MHz ultrasound, and quantitative analysis of fiber population density and diameter was performed. Gels exposed and fixed in the presence of ultrasound exhibited an increase in density of 65 ± 26% (mean ± SD) at 4 W/cm2 (p <0.000001) accompanied by a decrease in fiber diameter of 27 ± 9% (p <0.000001). Gels fixed 15 min following ultrasound exposure showed no significant change in either density or diameter compared to unexposed gels, indicating that the ultrasound-induced change in fiber structure was reversible. Factor XIII-crosslinked fibrin gels exhibited no change in population density or diameter when exposed to ultrasound. These results indicate that ultrasound exposure causes reversible disaggregation of uncrosslinked fibrin fibers into smaller fibers, an effect that may alter flow resistance and create additional binding sites for fibrinolytic components, improving fibrinolytic efficacy.

 

  • References

  • 1 Blinc A, Francis CW, Trudnowski JL, Carstensen EL. Characterization of ultrasound-potentiated fibrinolysis in vitro. Blood 1993; 81: 2636-2643
    PubMedGoogle Scholar
  • 2 Francis CW, Onundarson PT, Carstensen EL, Blinc A, Meltzer RS, Schwarz K, Marder VJ. Enhancement of fibrinolysis in vitro by ultrasound. J Clin Invest 1992; 90: 2063-2068
    CrossrefPubMedGoogle Scholar
  • 3 Lauer CG, Burge R, Tang DB, Bass BG, Gomez ER, Alving BM. Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis. Circulation 1992; 86: 1257-1264
    CrossrefPubMedGoogle Scholar
  • 4 Nilsson A-M, Odselius R, Roijer A, Olsson SB. Proand antifibrinolytic effects of ultrasound on streptokinase-induced thrombolysis. Ultrasound Med Biol 1995; 21: 833-840
    CrossrefPubMedGoogle Scholar
  • 5 Olsson SB, Johansson B, Nilsson A-M, Olsson Ch, Roijer A. Enhancement of thrombolysis by ultrasound. Ultrasound Med Biol 1994; 20: 375-382
    CrossrefPubMedGoogle Scholar
  • 6 Luo H, Steffen W, Cercek B, Arunasalam S, Maurer G, Siegel RJ. Enhancement of thrombolysis by external ultrasound. Am Heart J 1993; 125: 1564-1569
    CrossrefPubMedGoogle Scholar
  • 7 Harpaz D, Chen X, Francis CW, Meltzer RS. Ultrasound accelerates urokinase-induced thrombolysis and reperfusion. Am Heart J 1994; 127: 1211-1219
    CrossrefPubMedGoogle Scholar
  • 8 Harpaz D, Chen X, Francis CW, Marder VJ, Meltzer RS. Ultrasound enhancement of thrombolysis and reperfusion in vitro. J Am Coll Cardiol 1993; 21: 1507-1511
    CrossrefPubMedGoogle Scholar
  • 9 Rosenschein U, Bernstein JJ, DiSegni E, Kaplinsky E, Bemheim J, Rozenz-sajn sajn. Experimental ultrasonic angioplasty: Disruption of atherosclerotic plaques and thrombi in vitro and arterial recanalization in vivo. J Am Coll Cardiol 1990; 15: 711-717
    CrossrefPubMedGoogle Scholar
  • 10 Komowski R, Meltzer RS, Chemine A, Vered Z, Battler A. Does external ultrasound accelerate thrombolysis? Results from a rabbit model. Circulation 1994; 89: 339-344
    CrossrefPubMedGoogle Scholar
  • 11 Ariani M, Fishbein MC, Chae JS, Sadeghi H, Michael AD, Dubin SB, Siegel RJ. Dissolution of peripheral arterial thrombi by ultrasound. Circulation 1991; 84: 1680-1688
    CrossrefPubMedGoogle Scholar
  • 12 Francis CW, Blinc A, Lee S, Cox C. Ultrasound accelerates transport of recombinant tissue plasminogen activator into clots. Ultrasound Med Biol 1995; 21: 419-424
    CrossrefPubMedGoogle Scholar
  • 13 Siddiqi F, Blinc A, Braaten J, Francis CW. Ultrasound increases flow through fibrin gels. Thromb Haemost 1995; 73: 495-498
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 14 Zidansek A, Blinc A. The influence of transport parameters and enzyme kinetics of the fibrinolytic system on thrombolysis: Mathematical modelling of two idealised cases. Thromb Haemost 1991; 65: 553-559
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 15 Nishino N, Scully MF, Rampling MW, Kakkar VV. Properties of thrombolytic agents in vitro using a perfusion circuit attaining shear stress at physiological levels. Thromb Haemost 1990; 64: 550-555
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Blinc A, Planinsic G, Keber D, Jarh O, Lahajnar G, Zidansek A, Demsar F. Dependence of blood clot lysis on the mode of transport of urikinase into the clot – A magnetic resonance imaging study in vitro. Thromb Haemost 1991; 65: 549-552
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Carr ME, Shen LL, Hermans J. Mass-length ratio of fibrin fibers from gel permeation and light scattering. Biopolymers 1977; 16: 01-15
    CrossrefPubMedGoogle Scholar
  • 18 Doolittle RF. Fibrinogen and fibrin. In: Haemostasis and Thrombosis. Bloom AL, Thomas DP. (eds). New York: Churchill Livingstone; 1981. p 163
    Google Scholar
  • 19 Ferry JD, Morrison PR. Preparation and properties of serum and plasma proteins. VIII. The conversion of human fibrinogen to fibrin under various conditions. J Amer Chem Soc 1947; 69: 388-400
    CrossrefPubMedGoogle Scholar
  • 20 Baradet TC, Haselgrove JC, Weisel JW. Three-dimensional reconstruction of fibrin clot networks from stereoscopic intermediate voltage electron microscope images and analysis of branching. Biophys 1995; J 68: 1551-1560
    CrossrefPubMedGoogle Scholar
  • 21 Schwartz ML, Pizzo SV, Hill RL, McKee PA. The effect of fibrin-stabilizing factor on the subunit structure of human fibrin. J Clin Invest 1971; 50: 1506-1513
    CrossrefPubMedGoogle Scholar
  • 22 Schwartz ML, Pizzo SV, Hill RL, McKee PA. Human factor XIII from plasma and platelets. Molecular weights, subunit structures, proteolytic activation, and cross-linking of fibrinogen and fibrin. J Biol Chem 1973; 248: 1395-1407
    PubMedGoogle Scholar
  • 23 Weber K, Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem 1969; 244: 4406-4412
    PubMedGoogle Scholar
  • 24 Coleman XIII JR. Biological applications: Sample preparation and quantitation. In: Practical Scanning Electron Microscopy. Electron and Ion Microprobe Analysis. Goldstein JI, Newbury DE, Colby JW, Yakowitz H, Lifshin E, Coleman JR. (eds). New York: Plenum Press; 1975. p 491
    CrossrefGoogle Scholar
  • 25 Francis CW, Marder VJ. Rapid formation of large molecular weight apolymers in cross-linked fibrin induced by high factor XIII concentrations. Role of platelet factor XIII. J Clin Invest 1987; 80: 1459-1465
    CrossrefPubMedGoogle Scholar
  • 26 Hantgan RR, Hermans J. Assembly of fibrin. A light scattering study. J Biol Chem 1979; 254: 11272-11281
    PubMedGoogle Scholar
  • 27 Hantgan R, McDonagh J, Hermans J. Fibrin assembly. Ann NY Acad Sci 1983; 408: 344-366
    CrossrefPubMedGoogle Scholar
  • 28 Higgins DL, Lewis SD, Shafer JA. Steady state kinetic parameters for the thrombin-catalyzed conversion of human fibrinogen to fibrin. J Biol Chem 1983; 258: 9276-9282
    PubMedGoogle Scholar
  • 29 Lewis SD, Shields PP, Shafer JA. Characterization of the kinetic pathway for liberation of fibrinopeptides during assembly of fibrin. J Biol Chem 1985; 260: 10192-10199
    PubMedGoogle Scholar
  • 30 Janmey PA, Bale MD, Ferry JD. Polymerization of fibrin: analysis of lightscattering data and relation to a peptide release. Biopolymers 1983; 22: 2017-2019
    CrossrefPubMedGoogle Scholar
  • 31 Wolfe JK, Waugh DF. Relations between enzymatic and association reactions in the development of bovine fibrin clot structure. Arch Biochem Biophys 1981; 211: 125-142
    CrossrefPubMedGoogle Scholar
  • 32 Collet J-P, Woodhead JL, Soria J, Soria C, Mirshahi M, Caen JP, Weisel JW. Fibrinogen Dusart: Electron microscopy of molecules, fibers and clots, and visoelastic properties of clots. Biophys J 1996; 70: 500-510
    CrossrefPubMedGoogle Scholar
  • 33 Hasegawa N, Sasaki S. Location of the binding site “b” for lateral polymerization of fibrin. Thromb Res 1990; 57: 183-195
    CrossrefPubMedGoogle Scholar
  • 34 Gorkun OV, Veklich YI, Medved’ LV, Henschen AH, Weisel JW. Role of the aC domains of fibrin in clot formation. Biochemistry 1994; 33: 6986-6997
    CrossrefPubMedGoogle Scholar
  • 35 Langer BG, Weisel JW, Dinauer PA, Nagaswami C, Bell WR. Deglycosylation of fibrinogen accelerates polymerization and increases lateral aggregation of fibrin fibers. J Biol Chem 1988; 263: 15056-15063
    PubMedGoogle Scholar
  • 36 Gollwitzer R, Karges HE, Hӧrmann H, Kuhn K. Electron microscopic investigations on soluble and insoluble bovine fibrin. Biochim Biophys Acta 1970; 207: 445-455
    CrossrefPubMedGoogle Scholar
  • 37 National Council on Radiation Protection and Management. NRCP Report No. 113. Exposure criteria for medical diagnostic ultrasound. I. Criteria based on thermal mechanisms. Bethesda; Maryland: 1992
    Google Scholar
  • 38 Carstensen EL, Miller MW, Linke CA. Biological effects of ultrasound. J Biol Phys 1974; 02: 173-192
    CrossrefPubMedGoogle Scholar
  • 39 Williams AR. Gel sectioning technique for evaluation of phonophoresis in vivo. Ultrasonics 1990; 28: 137-141
    CrossrefPubMedGoogle Scholar
  • 40 Skorton DJ, Collins SM, Greenleaf JF, Meltzer RS, O’Brien WD, Schnittger I, von Ramm OT. Ultrasound bioeffects and regulatory issues: An introduction for the echocardiographer. J Am Soc Echocardio 1988; 01: 240-251
    PubMedGoogle Scholar
  • 41 Carr Jr ME, Hardin CL. Fibrin has larger pores when formed in the presence of erythrocytes. Am J Physiol 1987; 253: H1069-H1073
    PubMedGoogle Scholar
  • 42 Siddiqi F, Braaten JV, Francis CW. Effects of ultrasound on binding of tissue plasminogen activator to fibrin. J Acoust Soc Am 1996; 99: 2466 (abstract).
    PubMedGoogle Scholar