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Thromb Haemost 1991; 65(05): 588-595
DOI: 10.1055/s-0038-1648195
Original Article
Schattauer GmbH Stuttgart

Evaluation of Pulmonary Accumulation of 51Chromium-Labelled Rat Platelets following Intravenous Application of ADP and Collagen

Andreas Klee
*   The University of Würzburg, Dept, of Experimental Surgery, Würzburg, FRG
,
Dirk Seiffge
**   The Dept. of Pharmacology, Hoechst AG, Werk Kalle-Albert, Wiesbaden, FRG
› Author Affiliations
Further Information

Publication History

Received 28 July 1990

Accepted after revision 15 January 1991

Publication Date:
24 July 2018 (online)

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Summary

We examined the effects of ADP- and collagen-induced pulmonary platelet embolism in the rat. Homologous 51Chromium-labelled platelets were used to monitor extracorporally the distribution of platelets in the circulation. For that purpose, collimated iodide scintillation detectors were placed above thorax (C1) and abdomen (C2). A dose-dependent increase in thoracic radioactivity, paralleled by a decrease in the abdomen, was observed after intravenous injection of ADP and collagen. This resulted in a shift of C1/C2, so that the effect of collagen was more pronounced (maximal increase of C1/C2 = 134%) than ADP (maximal increase of C1/C2 = 79%). The increase in thoracic radioactivity was caused by the uptake of platelets in the lung as was shown after administration of collagen (6-fold enrichment of labelled platelets). Lung platelet sequestration resulted in a dose-dependent thrombocytopenia. The ADP-and collagen-induced pulmonary platelet embolism reversibly provoked cardiovascular symptoms of shock: hypotension and bradycardia. Impaired gas exchange during platelet accumulation manifested itself in a reversible arterial hypoxaemia and hyper-capnia, followed by a weak acidosis. We were able to inhibit ADP-dependent thoracic platelet accumulation by ticlopidine in a dose-related manner as well as collagen-induced thoracic platelet accumulation by acetylsalicylic acid. The results indicate that behaviour of homologous labelled rat platelets in vivo can easily be monitored, thus offering the opportunity to investigate the effects of antiaggregatory drugs on platelets in their natural environment.

 

  • References

  • 1 Mason RG, Mohammad SF, Chuany HY, Richardson PD. The adhesion of platelets to subendothelium, collagen and artificial surfaces. Semin Thromb Hemostas 1976; 3: 98-116
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Yerstraete M, Vermylen J. Thromboembolism in extra- and intracerebral arteries. In: Thrombosis Verstraete M, Vermylen J. (eds) Pergamon Press; Oxford: 1984. pp 163-174
  • 3 Baker WF. Clinical aspects of disseminated intravascular coagulation: A clinician’s point of view. Semin Thromb Hemostas 1989; 15: 1557
    PubMedGoogle Scholar
  • 4 Baumgartner HR, Haudenschild C. Adhesion of platelets to subendothelium. Ann N Y Acad Sci 1972; 201: 22-36
    CrossrefPubMedGoogle Scholar
  • 5 Born GVR. Quantitative investigations into the aggregation of blood platelets. J Physiol 1962; 162: 67-68
    PubMedGoogle Scholar
  • 6 Didisheim P, Fuster V. Actions and clinical status of platelet suppressive agents. Sem Haematol 1978; 15: 55-72
    PubMedGoogle Scholar
  • 7 Honey AC, Lad N, Tuffin DP. Effect of indomethacin and dazoxiben on intravascular platelet aggregation in the anaesthetized rabbit. Thromb Haemostas 1986; 56: 80-85
    PubMedGoogle Scholar
  • 8 Smith GM. Involvement of 5-hydroxytryptamine in platelet aggregation in vivo in rats and guinea pigs. Thromb Haemostas 1989; 61: 463-467
    PubMedGoogle Scholar
  • 9 Martin JF, Sugett AJ, Leach E, Moncada S. The effect of prostacyclin on platelet aggregation and disaggregation in vivo. Thromb Res 1980; 18: 749-751
    CrossrefPubMedGoogle Scholar
  • 10 Ubatuba FB, Moncada S, Vane JR. The effect of prostacyclin (PGI2) on platelet behaviour, thrombus formation in vivo and bleeding time. Thromb Haemostas 1979; 41: 425-435
    PubMedGoogle Scholar
  • 11 Higgs EA, Higgs GA, Moncada S, Vane JR. Prostacyclin (PGI2) inhibits the formation of platelet thrombi in arterioles and venules of the hamster cheek pouch. Br J Pharmacol 1978; 63: 535-539
    CrossrefPubMedGoogle Scholar
  • 12 Buchanan MR, Hirsh J. A comparison of the effects of aspirin and dipyridamole on platelet aggregation in vivo and ex vivo. Thromb Res 1978; 13: 517-529
    CrossrefPubMedGoogle Scholar
  • 13 Kohler C, Wooding W, Ellenbogeh L. Intravenous arachidonate in the mouse - a model for the evaluation of antithrombotic drugs. Thromb Res 1976; 9: 67-80
    CrossrefPubMedGoogle Scholar
  • 14 Mallarky G, Smith GM. The involvement of platelets and the coronary vasculature in collagen-induced sudden death in rabbits. Thromb Haemostas 1985; 53: 70-74
    PubMedGoogle Scholar
  • 15 Davies O, Morley J, Page CP, Paul W. In vivo aggregation of guinea pig platelets. J Physiol 1981; 320: 3-4
    PubMedGoogle Scholar
  • 16 Bishop SP. Cardiovascular research. In: The Laboratory Rat (II) -Research Applications Baker HJ, Lindsey JR, Weisbroth SH. (eds) Academic Press; Orlando, FL: 1980. pp 162-180
  • 17 Yale CA, Torhorst JB. Critical bleeding and plasma volumes of adult germ-free rats. Lab Anim Sci 1972; 22: 497-502
    PubMedGoogle Scholar
  • 18 Heaton WA, Davis HH, Welch MJ, Mathias CJ, Joist JH, Sherman LA, Siegel BA. Indium-111: a new radionuclide label for studying human platelet kinetics. Br J Haematol 1979; 42: 613-622
    CrossrefPubMedGoogle Scholar
  • 19 Hawkins HJ, Wilson AG, Anderson MW, Eling TE. Uptake and metabolism of prostaglandins by isolated perfused lung. Species comparison and the role of plasma protein binding. Prostaglandins 1977; 14: 251-259
    CrossrefPubMedGoogle Scholar
  • 20 Wiegand HJ, Ottenwalder H, Bolt HM. The reduction of chromium (VI) to chromium (III) by glutathione: An intracellular redox pathway in the metabolism of the carcinogen chromate. Toxicology 1984; 33: 341-348
    CrossrefPubMedGoogle Scholar
  • 21 Dodds WJ. Platelet function in animals: Species specificities. In: Platelets: A Multidisciplinary Approach de Gaetano G. (ed) Raven Press; New York: 1970. pp 45-49
  • 22 Maffrand JP, Bemat A, Delebassee D, Defreyn G, Cazenave JP, Gordon JL. ADP plays a key role in thrombogenesis in rats. Thromb Haemostas 1988; 59: 225-230
    PubMedGoogle Scholar
  • 23 Holmes IB, Smith GM, Freuler F. The effect of intravenous adenosine diphosphate on the number of circulating platelets in experimental animals: Inhibition by prostaglandin E1, dipyridamole, SH-869 and VK-774. Thromb Haemostas 1977; 37: 36-46
    PubMedGoogle Scholar
  • 24 Joris I, Braunstein PW. Platelets and endothelium: Effect of collagen-induced platelet aggregates on pulmonary vessels. Exp Mol Pathol 1982; 37: 393-405
    CrossrefPubMedGoogle Scholar
  • 25 Dejana E, de Gaetano G, Bonaccorsi A. Role of the lung in the development of cardiovascular modifications during ADP infusion in the rat. Thromb Res 1977; 12: 47-57
    PubMedGoogle Scholar
  • 26 Butler KD, Shand RA, Wallis RB. The effects of modulation of prostanoid metabolism on the thoracic platelet accumulation induced by intravenous administration of collagen in the guinea-pig. Thromb Haemostas 1986; 56: 263-267
    PubMedGoogle Scholar
  • 27 Page CP, Paul W, Morley J. An in vivo model for studying platelet aggregation and disaggregation. Thromb Haemostas 1982; 47: 210-213
    PubMedGoogle Scholar
  • 28 Benigni A, Chiabrando C, Piccinelli A, Perico N, Gavinelli M, Furci L, Patino O, Abbate M, Bertani T, Remuzzi G. Increased urinary excretion of thromboxane B2 and 2,3-dinor-TxB2 in cyclosporin A nephrotoxicity. Kidney Int 1988; 34: 164-174
    CrossrefPubMedGoogle Scholar
  • 29 Landgraf MMC, Loy A, Christea C, Weber PC, Siess W, Herberg LL, Landgraf R. Aggregation and thromboxane B2 formation in platelets and vascular prostacyclin production from genetically obese rats. Prostaglandins 1981; 22: 521-536
    CrossrefPubMedGoogle Scholar
  • 30 Martin JF, Sugetti AJ, Jones PBC, Leach E. Effect of acetylsalicylic acid on platelet aggregation and thromboxane B2 production in flowing aortic blood in the rat studied with a filter loop technique. Thromb Res 1982; 27: 251-259
    CrossrefPubMedGoogle Scholar
  • 31 Johnson M, Walton PM, Cotton RC, Strachan CJL. Pharmacological evaluation of ticlopidine, a novel inhibitor of platelet function. Thromb Haemostas 1977; 38: 64-65 (Abstr)
    PubMedGoogle Scholar
  • 32 Vedelago HR, Mahadevappa VG. Mobilization of arachidonic acid in collagen-stimulated human platelets. Biochem J 1988; 256: 981-987
    CrossrefPubMedGoogle Scholar
  • 33 Geratz JD, Tidwell RR, Brinkhous KM, Mohammad SF, Dann O, Loewe H. Specific inhibition of platelet agglutination and aggregation by aromatic amidine compounds. Thromb Haemostas 1978; 39: 411-415
    PubMedGoogle Scholar
  • 34 Nunn B. Collagen-induced platelet aggregation: - Evidence against the essential role of platelet adenosine diphosphate. Thromb Haemostas 1979; 42: 1193-1206
    PubMedGoogle Scholar
  • 35 Mallarkey G, Smith GM. A comparative study of the involvement of the prostaglandin H2/thromboxane A2 pathway in intravascular platelet aggregation in guinea-pigs and rats. Br J Pharmacol 1985; 84: 425-430
    CrossrefPubMedGoogle Scholar