Thromb Haemost 2000; 83(02): 322-326
DOI: 10.1055/s-0037-1613806
Rapid Communication
Schattauer GmbH

An In-vitro Model to Study Device-induced Thrombosis and Embolism:

Evaluation of the Efficacy of Tirofiban, Aspirin, and Dipyridamole
Sivaprasad Sukavaneshvar
,
Kenneth A. Solen
,
Syed F. Mohammad
1   Department of Pathology, and Artificial Heart Research Laboratory, University of Utah, Salt Lake City, Utah, USA
› Author Affiliations
Further Information

Publication History

Received 12 June 1998

Accepted 12 October 1999

Publication Date:
11 December 2017 (online)

Summary

A bovine in-vitro model was developed to investigate device-induced thromboembolism (TE) and its pharmacological intervention, using a stent as a prototype device. Emboli were assessed continuously using a light-scattering microemboli detector (LSMD). Thrombus on the stent was assessed gravimetrically at the end of the experiment. The contribution of the stent as the predominant source of detectable thromboemboli in this model was verified by placing LSMD probes upstream and downstream of the stent. The effectiveness of ethylenedinitrilo-tetraacetic-acid (EDTA) and three anti-thrombogenic agents (aspirin, dipyridamole, and tirofiban) for mitigating device-induced TE was also assessed. The results show that 1) the model has potential to study device-induced TE and the efficacy of possible interventional strategies, 2) the LSMD is capable of continuous, non-invasive, real-time assessment of embolism, 3) the assessment of embolization may constitute an important part of evaluating hemocompatibility, 4) tirofiban is effective in reducing both stent-induced thrombosis and embolism above certain concentrations.

 
  • References

  • 1 Beythien C, Wolfram T, Hamm CW. In-vitro model to test the thrombogenecity of coronary stents. Thromb Res 1994; 75: 581-90.
  • 2 Freund M, Mantz F, Nicolini P, Gachet C, Mulvihill J, Meyer L, Beretz A, Cazenave JP. Experimental thrombosis on a collagen coated arterioarterial shunt in rats: a pharmacological model to study antithrombotic agents inhibiting thrombin formation and platelet deposition. Thromb Haemost 1993; 69: 515-21.
  • 3 Pan M, Suarez de lezo J, Velasco F, Romero M, Medina A, Segura J, Hernandez E, Pavlovic D, Melian F, Gallardo A, Zayas R, Ruiz M, Torres A. Reduction of thrombotic and hemorrhagic complications after stent implantation. Am Heart J 1996; 132: 1119-26.
  • 4 Peng Y. Characterization of microemboli in whole blood by a new laser light-scattering technique. M. S. Thesis 1994. Brigham Young University.;
  • 5 Reynolds LO, Simon T. Size distribution measurements in microaggregates in stored whole blood. Transfusion 1980; 20: 669-78.
  • 6 Reynolds LO. Light scattering detection of microemboli. Trans 11th Ann Meeting Soc Biomat and 17th Internat Biomat Symp 1985; 08: 20.
  • 7 Sukavaneshvar S, Zheng Y, Solen KA. Developments in emboli detection based on light-scattering. Submitted to Review of scientific instruments.
  • 8 Zheng Y, Mohammad S, Solen KA. The light-scattering whole blood aggregometer: A novel device for assessment of platelet aggregation in undiluted blood. Arch Pathol Lab Med 1998; 122: 880-6.
  • 9 Baim BS, Carrozza Jr JP. Stent thrombosis: Closing in on the best preventive treatment. Circulation 1997; 95: 1098-100.
  • 10 Elkeles RS, Hampton JR, Honour AJ, Mitchell JR, Prichard JS. Effect of a pyrimido-pyramidine compound on platelet behaviour in vitro and in-vivo. Lancet 1968; 02: 751-4.
  • 11 Hladovec J. Antithrombotic drugs in thrombosis models. Boca Raton: CRC Press Inc; 1989
  • 12 Turner NA, Moake JL, Kamat SG, Schafer AI, Kleiman NS, Jordan R, McIntire LV. Comparative real-time effects on platelet adhesion and aggregation under flowing conditions of in vivo aspirin, heparin, and monoclonal antibody fragment against glycoprotein IIb-IIIa. Circulation 1995; 91: 1354-62.
  • 13 Barrett JS, Murphy G, Peerlinck K, De Lepeleire I, Gould RJ, Panebianco D, Hand E, Deckmyn H, Vermylen J, Arnout J. Pharmacokinetics and pharmacodynamics of MK-383, a selective non-peptide platelet glycoprotein- IIb/IIIa receptor antagonist in healthy men. Clin Pharmacol Ther 1994; 56: 377-88.
  • 14 Gibson CM, Goel M, Cohen DJ, Piana RN, Deckelbaum LI, Harris KE. King SB-3rd. Six-month angiographic and clinical follow-up of patients prospectively randomized to receive either tirofiban or placebo during angioplasty in the RESTORE trial. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis. J Am Coll Cardiol 1998; 32: 28-34.
  • 15 The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis. Circulation 1997; 96: 1445-53.
  • 16 The EPISTENT Investigators. Randomized controlled trial to assess safety of coronary stenting with use of abciximab. Lancet 1998; 339: 436-43.
  • 17 Sukavaneshvar S, Solen KA, Mohammad SF. Device induced thromboembolism in a bovine in vitro coronary stent model. ASAIO J 1998; 44: M393-6.
  • 18 Xiao Z, Theroux P, Frojmovic M. Modulation of platelet-neutrophil interaction with pharmacological inhibition of fibrinogen binding to platelet GPIIb/IIIa receptor. Thromb Haemost 1999; 81: 281-5.
  • 19 Sukavaneshvar S, Rosa GM, Solen KA. Thrombosis and embolism in a stenosis-stent model: contribution of hemodynamics. Annals of Biomedical Engineering, in press.
  • 20 Sukavaneshvar S, Solen KA. Effects of hemodynamics on thromboembolism in coronary stents and prototype flow cells in vitro. ASAIO J 1998; 44: M388-92.
  • 21 Sukavaneshvar S, Zheng Y, Rosa G, Mohammad SF, Solen KA. Thromboembolism associated with sudden increases in flow in a coronary stent ex-vivo shunt model. ASAIO J, in press.