Download PDF
Thromb Haemost 1995; 74(03): 974-979
DOI: 10.1055/s-0038-1649858
Original Article
Vessel Wall
Schattauer GmbH Stuttgart

Aurintricarboxylic Acid Reduces Platelet Deposition in Stenosed and Endothelially Injured Rabbit Carotid Arteries more Effectively than other Antiplatelet Interventions

Palolo Golino
The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Massimo Ragni
The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Plinio Cirillo
The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Immacolata Pascucci
The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Michael D Ezekowitz
1   The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Aruna Pawashe
1   The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Annalisa Scognamiglio
The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Leonardo Pace
2   The Division of Nuclear Medicine, 2nd School of Medicine, University of Naples, Italy
,
Angela Guarino
The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
,
Massimo Chiariello
The Department of Internal Medicine, Division of Cardiology, Yale University, New Haven, CT, USA
› Author Affiliations
Further Information

Publication History

Received 30 December 1994

Accepted after resubmission 28 April 1995

Publication Date:
09 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

In the present study we tested the effects of different antithrombotic interventions on platelet deposition in experimentally-stenotic rabbit carotid arteries with endothelial injury. Platelet deposition, quantitated by labeling autologous platelets with 111 In-oxine, was significantly reduced compared to control animals by all interventions tested, i.e., R 68070, a drug with thromboxane A2 synthase and receptor blocking properties, BN 52021, a PAF receptor antagonist, aurintricarboxylic acid (ATA), an inhibitor of platelet glycoprotein (Gp) Ib/von Wille-brand factor (vWf) interaction, AZ-1, a monoclonal antibody against rabbit GPIIb/IIIa, the platelet receptor for fibrinogen, and AP-1, a monoclonal antibody against rabbit tissue factor. ATA was significantly more effective than all the other interventions in reducing platelet deposition in the stenotic vessels. We conclude that inhibition of Gp Ib/vWf interaction may be a more suitable target for antithrombotic therapy under conditions of high shear stress, like those produced in this model.

 

  • References

  • 1 Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM. Specific platelet mediators and unstable coronary artery lesions: Experimental evidence and clinical implications. Circulation 1989; 80: 198-205
    CrossrefPubMedGoogle Scholar
  • 2 Hirsh PD, Hillis LD, Campbell WB, Firth BG, Willerson JT. Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J med 1981; 304: 685-691
    CrossrefPubMedGoogle Scholar
  • 3 Van den Berg EK, Schmitz JM, Benedict CR, Malloy CR, Willerson JT, Dehmer GJ. Transcardiac serotonin concentration is increased in selected patients with limiting angina and complex coronary lesion morphology. Circulation 1989; 79: 116-124
    CrossrefPubMedGoogle Scholar
  • 4 Folts JD, Crowell Jr EB, Rowe CG. Platelet aggregation in partially obstructed vessels and its elimination by aspirin. Circulation 1976; 54: 365-370
    CrossrefPubMedGoogle Scholar
  • 5 Golino P, Buja LM, Ashton JH, Kulkarni P, Taylor A, Willerson JT. Effect of thromboxane and serotonin reeeptor antagonists on intraeoronary platelet deposition in dogs with experimentally stenosed coronary arteries. Circulation 1988; 78: 701-711
    CrossrefPubMedGoogle Scholar
  • 6 Ashton JH, Schmitz JM, Campbell WB, Ogletrce ML, Raheja S, Taylor AL, Fitzgerald C, Buja LM, Willerson JT. Inhibition of cyclic How variations in stenosed canine coronary arteries by thromboxane A,/prostaglandin H , receptor antagonists. Circ Res 1986; 59: 568-578
    CrossrefPubMedGoogle Scholar
  • 7 Ashton JH, Benedict CR, Eitzgerald C, Raheja S, Taylor A, Campbell W, Buja LM, Willerson JT. Serotonin is a mediator of cyclic flow variations in stenosed canine coronary arteries. Circulation 1986; 73: 572-578
    CrossrefPubMedGoogle Scholar
  • 8 Eidt JL, Allison PNoble S, Ashton HT, Golino P, MeNatt J, Buja LM, Willerson JT. Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury. J Clin Invest 1989; 84: 18-25
    CrossrefPubMedGoogle Scholar
  • 9 Yao SK, Ober J, Benedict CR, Rosolowsky M, Anderson HV, Cui K, Maffrand JP, Campbell WB, Bula LM, Willerson JT. ADP plays an important role in mediating platelet aggregation and cyclic flow variations in vivo in stenosed and endothelium-injured canine coronary arteries. Circ Res 1992; 70: 39-48
    CrossrefPubMedGoogle Scholar
  • 10 Golino P, Ambrosio G, Ragni M, Pascucci I, Triggiani M, Oriente A, McNatt J, Buja LM, Conderelli M, Chiaricllo M, Willerson JT. Short-term and long-term role of platelet activating factor as a mediator of in vivo platelet aggregation. Circulation 1993; 88: 1205-1214
    CrossrefPubMedGoogle Scholar
  • 11 Golino P, Ashton JH, Buja LM. Local platelet activation causes vasoconstriction of large cpicardial canine coronary arteries in vivo: thromboxane A2and serotonin are possible mediators. Circulation 1989; 79: 154-166
    CrossrefPubMedGoogle Scholar
  • 12 Pawashe AB, Golino P, Ambrosio G, Migliaccio F, Ragni M, Pascucci I, Chiariello M, Bach R, Garen A, Konigsberg WK, Ezekowitz MD. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ Res 1994; 74: 56-63
    CrossrefPubMedGoogle Scholar
  • 13 Kroll MH, Harris TS, Moake JL, Handin RI, Schafer AI. von Willebrand factor binding to platelet Gp lb initiates signals for platelet activation. J Clin Invest 1991; 88: 1568-1573
    CrossrefPubMedGoogle Scholar
  • 14 Ware JA, Johnson PC, Smith M, Salzman EW. Effect of common agonists on cytoplasmic ionized calcium concentration in platelets. J Clin Invest 1986; 77: 878-886
    CrossrefPubMedGoogle Scholar
  • 15 Plow EF, Marguerie GA. The induction of the fibrinogen receptor on human platelets by epinephrine and the combination of epinephrine and ADP. J Biol Chem 1980; 225: 10971-1097
    PubMedGoogle Scholar
  • 16 Golino P, Ambrosio G, Pascucci I, Ragni M, Russolillo E, Chiariello M. Experimental carotid stenosis and endothelial injury in the rabbit: an in vivo model to study intravascular platelet aggregation. Thromb Haemost 1992; 67: 302-305
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Golino P, Cappelli M, Ambrosio G, Ragni M, Russolillo E, Condorelli M, Chiariello M. Endothelium-Derived Relaxing Factor Modulates Platelet Aggregation in an In Vivo Model of Recurrent Platelet Activation. Circ Res. 1992; 71: 1447-1456
    PubMedGoogle Scholar
  • 18 Thakur ML, Welch MJ, Joist JH, Coleman RE. Indium-HI labeled platelets: Studies on preparation and evaluation of in vitro and in vivo functions. Thromb Res 1976; 9: 345-352
    CrossrefPubMedGoogle Scholar
  • 19 De Clerck F, Beetens J, de Chaffoy de CourcellesD, Freyne E, Janssen PP A J. R 68070: Thromboxane A2synthase inhibition and thromboxane A2/prostaglandin endoperoxide receptor blockade combined in one molecule I. Biochemical profile In vitro. Thromb Haemost 1989; 61: 35-42
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Golino P, Ambrosio G, Villari B, Ragni M, Focaccio A, Pace L, De Clerck F, Condorelli M, Chiariello M. Endogenous prostaglandin endoperoxides may alter infarct size in the presence of thromboxane synthase inhibition. Studies in a rabbit model of coronary artery occlusion-reperfusion J Am Coll Cardiol 1993; 21: 493-502
    CrossrefPubMedGoogle Scholar
  • 21 Braquet P, Etienne A, Touvay C, Bourgain RH, Lefort J. Vargaftig BB Involvement of platelet activating factor in respiratory anaphylaxis, demonstrated by the PAF-acether antagonist BN 52021. Lancet 1986; 1: 1501
    PubMedGoogle Scholar
  • 22 Lagente V, Touvay C, Randon J. Interference of the PAF-aeether antagonist BN 52021 with passive anaphylaxis in the guinea pig. Prostaglandins 1987; 33265-33274
    PubMedGoogle Scholar
  • 23 Phillips MD, Moake JL, Nolaseo L, Turner N. Aurintricarboxylie acid: A novel inhibitor of the association of von Willebrand factor and platelets. Blood 1988; 72: 1898-1903
    PubMedGoogle Scholar
  • 24 Strony J, Phillips M, Brands D, Moake J, Adelman B. Aurintricarboxylic acid in a canine model of coronary artery thrombosis. Circulation 1990; 81: 1106-1114
    CrossrefPubMedGoogle Scholar
  • 25 Badimon L, Badimon JJ. Mechanisms of arterial thrombosis in nonparallel streamlines: Platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental studies in the pig model J Clin Invest 1989; 84: 1134-1144
    CrossrefPubMedGoogle Scholar
  • 26 Goldsmith HE, Karino T. Quantitative cardiovascular studies: Clinical and research application of cngencering principles. Baltimore: MD: University Park; 1978: 289-351
    Google Scholar
  • 27 Goldsmith HL, Turitto VT. Rheological aspects of thrombosis and hemostasis: basic principles and applications. Haemostasis 1986; 55: 415-435
    PubMedGoogle Scholar
  • 28 Strony J, Beaudoin A, Brands D, Adelman B. Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. Am J Physiol 1993; 265: H1787-H1796
    PubMedGoogle Scholar
  • 29 Badimon L, Badimon JJ, Galvez A, Chesebro JH, Fuster V. Influenee of arterial damage and wall shear rate on platelet deposition: Ex vivo study in a swine model. Arteriosclerosis 1986; 6: 312-321
    CrossrefPubMedGoogle Scholar
  • 30 Weiss HJ, Turitto VT, Baumgartner HR. Role of shear rate and platelets in promoting fibrin formation on rabbit subendothelium. J Clin Invest 1986; 78: 1072-1083
    CrossrefPubMedGoogle Scholar
  • 31 Ruggeri ZM. Receptor-specific antiplatelet therapy. Circulation 1989; 80: 1920-1922
    CrossrefPubMedGoogle Scholar
  • 32 Lewis Jr HD, Davies JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med 1983; 309: 396-403
    CrossrefPubMedGoogle Scholar
  • 33 Willerson JT, Yao SK, McNatt J, Benedict CR, Anderson HV, Golino P, Murphree SS, Buja LM. Frequency and severity of cyclic flow alterations and platelet aggregation predict the severity of neointimal proliferation following experimental coronary stenosis and endothelial injury. Proc Natl AcadSci USA 1991; 88: 10624-10628
    CrossrefPubMedGoogle Scholar