Thromb Haemost 1985; 53(03): 423-427
DOI: 10.1055/s-0038-1661329
Original Article
Schattauer GmbH Stuttgart

Studies of Suloctidil in Experimental Thrombosis in Baboons

Stephen R Hanson
The Division of Cardiovascular Research and Roon Research Center for Arteriosclerosis and Thrombosis, Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, CA, USA
,
Laurence A Harker
The Division of Cardiovascular Research and Roon Research Center for Arteriosclerosis and Thrombosis, Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, CA, USA
› Author Affiliations
Further Information

Publication History

Received 29 November 1984

Accepted 27 March 1985

Publication Date:
18 July 2018 (online)

Summary

Suloctidil has been evaluated in the baboon for its antithrombotic efficacy using models of both acute and chronic arterial thrombogenesis. Acute thrombus formation was initiated by Dacron vascular grafts inserted as extension segments into chronic arteriovenous shunts. 111In-platelet deposition was measured by scintillation camera imaging for one hour. The results after oral administration of suloctidil (100 mg/kg/d in two divided doses) were not different from control studies. Moreover, concurrent heparin anticoagulation did not affect 111In-platelet deposition compared with control data. In contrast, ticlopidine (20 mg/ kg/d) significantly decreased platelet deposition that was reduced further by the addition of heparin.

Chronic arterial-thromboembolism was initiated by segments of polyurethane (Biomer) cannula introduced into chronic arteriovenous shunts. Thrombus formation by the polyurethane cannula was measured as 111In-platelet turnover (corrected for removal of senescent platelets). Cannula platelet consumption was unaffected by suloctidil (20 mg/kg/d given in two divided doses for two days preceding and throughout the period of platelet survival measurement). In contrast, dipyridamole (10 mg/ kg/d) and sulfinpyrazone (100 mg/kg/d) completely interrupted cannula platelet consumption.

We conclude that suloctidil probably has little or no effect on platelet-dependent thrombus formation.

 
  • References

  • 1 Hanson SR, Harker LA. Effect of dazoxiben on arterial graft thrombosis in the baboon. Br J Clin Pharmacol 1983; 15: 57S-60S
  • 2 Harker LA, Hanson SR. Experimental arterial thromboembolism in baboons. Mechanism, quantitation, and pharmacologic prevention J Clin Invest 1979; 64: 559-569
  • 3 Roba J, Defreyn G, Biagi G. Antithrombotic activity of suloctidil. Thromb Res 1983; Suppl 06: 53-58
  • 4 Roba J, Claeys M, Lambelin G. Antiplatelet and antithrombotic effects of suloctidil. Eur J Pharmacol 1976; 37: 265-274
  • 5 Roba J, Bourgain R, Andries R, Claeys M, Van Opstal W, Lambelin G. Antagonism by suloctidil of arterial thrombus formation in rats. Thromb Res 1976; 9: 585-594
  • 6 Potvliege PR, Bourgain RH. Inhibition by suloctidil of the early arterial wall reactions induced by local thrombosis. Eur J Rheumatol Inflammation 1979; 2: 204-207
  • 7 Gurewich V, Lipinski B. Evaluation of the antithrombotic properties of suloctidil in comparison with aspirin and dipyridamole. Thromb Res 1976; 9: 101-108
  • 8 Tuma RF, Wiedeman MP, Mayrovitz HN. Microvascular responses to suloctidil. The Physiologist 1976; 19: 394
  • 9 Col-de Beys C, Ferrant A, Moriau M. Effects of suloctidil on platelet survival time following cardiac valve replacement. Thromb Haemostas 1981; 46: 550-553
  • 10 Ciavarella N, Antoncecchi S, D’Elia N, Ettorre C, Raniere P, Manzini A. Normalization by suloctidil of decreased platelet survival in patients with heart prosthetic valves in randomized controlled double blind trial. Thromb Haemostas 1981; 46: 308 (Abstr.)
  • 11 De Gaetano G, Miragliotta G, Roncucci R, Lansen J, Lambelin G. Suloctidil: A novel inhibitor of platelet aggregation in human beings. Thromb Res 1976; 8: 361-371
  • 12 Chamone DA F, Vermylen J. The induction of platelet aggregates in healthy subjects by venous occlusion. Thromb Haemostas 1977; 38: 132 (Abstr.)
  • 13 Potvliege PR, Bourgain RH. The effect of suloctidil on blood platelet ultrastructure in man and rat. Br J Exp Pathol 1978; 59: 540-543
  • 14 Moriau M, Col-deBeys C, Pardonge E, Ferrant A. Clinical and biological activity of the antiplatelet agent suloctidil in treatment of idiopathic recurrent vein thrombosis. Thromb Haemostas 1982; 47: 27-31
  • 15 Jones NA G, De Haas H, Zahavi J, Kakkar VV V. double-blind trial of suloctidil v. placebo in intermittent claudication. Br J Surg 1982; 69: 38-40
  • 16 Hanson SR, Harker LA, Ratner BD, Hoffman AS. In vivo evaluation of artificial surfaces with a nonhuman primate model of arterial thrombosis. J Lab Clin Med 1980; 95: 289-304
  • 17 Murphy EA, Francis ME. The estimation of blood platelet survival. II. The multiple hit model. Thrombos Diathes Haemorrh 1971; 25: 53-80
  • 18 Domhorst AC. The interpretation of red cell survival curves. Blood 1951; 6: 1284-1292
  • 19 Heyns Adu, Lotter MD, Badenhorst PN. Platelet Imaging. In Methods in Hematology: Measurement of Platelet Function. Harker LA, Zimmermann TS. (Eds) Churchill Livingston; Edinburgh: 1983. 8 216-234
  • 20 Hoffman AS, Cohn D, Hanson SR, Harker LA, Horbett TA, Ratner BD, Reynolds LO. Application of radiation-grafted hydrogels as blood-contacting biomaterials. Rad Phys Chem 1983; 22: 267-283
  • 21 Hanson SR, Reidy MA, Hattori A, Harker LA. Pharmacologic modification of acute vascular graft thrombosis. Scan Electron Microsc 1982; 2: 773-779
  • 22 Hampton JW, Matthews C. Similarities between baboon and human blood clotting. J Appl Physiol 1966; 21: 1713-1716
  • 23 Todd ME, McDevitt E, Goldsmith EI. Blood-clotting mechanisms of nonhuman primates: choice of the baboon model to simulate man. J Med Primatol 1972; 1: 132-141
  • 24 Hanson SR, Harker LA, Bjomsson TD. Effects of plateletmodifying drugs on arterial thromboembolism in baboons: Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition. J Clin Invest. 1985 (In press)
  • 25 Chatelain P, Ruysschaert JM. Suloctidil-phospholipid interaction in bilayer membranes: Effects on lipid dynamics. Biochem Pharmacol 1981; 30: 313-317
  • 26 Godfraind T. Actions of suloctidil and of Ca-antagonist cinnarizine on the rat aorta. Arch Int Pharmacodyn 1976; 221: 342-343
  • 27 Malaisse W. Calcium antagonists. Effect of suloctidil Arch Int Pharmacodyn 1977; 228: 339-344
  • 28 Roba J, Cavalier R, Herrn M, Lambelin G. Suloctidil: Relationship between pharmacokinetics and antithrombotic effect. Thromb Res 1983; Suppl 06: 113-118