Thromb Haemost 1985; 53(03): 351-355
DOI: 10.1055/s-0038-1661313
Original Article
Schattauer GmbH Stuttgart

Smooth Muscle Proliferation in Chronically Injured Canine Pulmonary Arteries Is Reduced by a Potent Platelet Aggregation Inhibitor U-53,059

Robert G Schaub
1   The Department of Atherosclerosis and Thrombosis Research, The Upjohn Company, Kalamazoo, MI, USA
,
James C Keith Jr
2   The Department of Veterinary Biology, Virginia Polytechnical Institute, Blacksburg, VA, USA
,
Carol A Simmons
1   The Department of Atherosclerosis and Thrombosis Research, The Upjohn Company, Kalamazoo, MI, USA
,
Clarence A Rawlings
3   The Department of Small Animal Medicine, The University of Georgia, Athens, GA, USA
› Author Affiliations
Further Information

Publication History

Received 06 September 1984

Accepted 11 March 1985

Publication Date:
18 July 2018 (online)

Summary

Dirofilaria immitis (DI) infection chronically injures canine pulmonary arteries. This injury produces endothelial cell loss, platelet/leukocyte adhesion, and smooth muscle proliferation. In the present study we assessed the effect of the cyclooxygenase inhibitor, U-53,059, on platelet function, platelet kinetics, coagulation, and smooth muscle proliferation in DI infected dogs.

Platelet aggregation to the combination of arachidonic acid/ ADP was significantly inhibited by U-53,059. Coagulation and hematologic parameters were not effected by either DI infection or U-53,059 treatment. Platelet survival and the number of platelet dense granules were reduced in DI infection. Quantification of the lesions demonstrated that U-53,059 reduced both severity and density compared to non-treated dogs. U-53,059 is a potent and effective inhibitor of platelet aggregation which modifies smooth muscle proliferation produced by chronic vascular injury.

 
  • References

  • 1 Schaub RG, Simmons CA. Medial smooth muscle proliferation in the balloon injured rabbit aorta: Effect of thiazole compound with platelet inhibitory activity. Thromb Haemostas 1984; 51: 75-78
  • 2 Schaub RG, Keith Jr JC, Rawlings CA. Myointimal proliferation in canine pulmonary arteries. Am J Pathol 1981; 103: 440-449
  • 3 Schaub RG, Keith Jr JC, Rawlings CA. The effect of acetylsalicylate acid on vascular damage and myointimal proliferation in canine arteries subjected to chronic injury by Dirofiliaria immitis. Am J Vet Res 1983; 44: 449-454
  • 4 Sharefkin J, Rich NM. Technical consideration in the study of 111Indium oxine labelled platelet survival patterns in dogs. Lab Anim Sci 1982; 32: 183-186
  • 5 Wilkinson AR, Hawker RJ, Hawker LM. 111Indium labelled canine platelets. Thromb Res 1978; 13: 175-182
  • 6 Schaub RG, Rawlings CA, Stewart GJ. Scanning electron microscopy of canine pulmonary arteries and veins. Am J Vet Res 1980; 41: 1441-1446
  • 7 Madewell BR, Feldman BF, O’Neill S. Coagulation abnormalities in dogs with neoplastic disease. Thromb Haemostas 1980; 44: 35-38
  • 8 Niewiarowski S, Gurewich V. Laboratory identification of intravascular coagulation. J Lab Clin Med 1971; 77: 665-676
  • 9 Fry D. Acute vascular endothelial changes associated with increase blood velocity gradients. Cir Res 1968; 22: 165-197
  • 10 Motomiya M, Karino T. Flow patterns in the human carotid artery bifurcation. Stroke 1984; 15: 50-56
  • 11 Cornhill JF, Roach MR. A quantitative study of the localization of atherosclerotic lesions in the rabbit aorta. Atherosclerosis 1976; 23: 489-501
  • 12 Lutz RJ, Cannon JN, Bischoff KB, Dedrick RL, Stiles RK, Fry DL. Wall shear stress distribution in a model canine artery during steady flow. Cir Res 1977; 41: 391-399
  • 13 Nishizawa EE, Mendoza AR, Honohan T, Annis KA. A thiazole compound with potential anti-thrombotic activity. Thromb Haemostas 1982; 47: 173-176
  • 14 Linet O, Eckert S, Gruber C, Huang D. The effects of an oral antiplatelet agent, U-53,059 in man. Circulation 1982; 66: 11-323
  • 15 Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on homocysteine-induced endothelial injury and arteriosclerosis in baboons. Circ Res 1983; 53: 731-739
  • 16 Winocour PD, Kinlough-Rathbone RL, Richardson M, Mustard JF. Reversal of shortened platelet survival in rats by the antifibrinolytic agent epsilon aminocaproic acid. J Clin Invest 1983; 71: 159-164
  • 17 Steele P, Battock D, Genton E. Effects of clofibrate and sulfinpyrazone on platelet survival in coronary artery disease. Circulation 1975; 52: 473-476
  • 18 Barrett PA, Butler KD. Shortening of platelet survival by induced hypercholesterolemia in rabbits and its prolongation by Anagrelide. Thromb Haemostas 1983; 50: 656-659
  • 19 Davis RG, White JG. Localization of 5-hydroxytryptamine in blood platelets. A radioautographic an ultrastructural study Br J Haematol 1968; 15: 93-99
  • 20 Martin JH, Carson FL, Race GJ. Calcium containing platelet granules. J Cell Biol 1974; 60: 775-777
  • 21 White JG, Gerrard JM. Ultrastructural features of abnormal blood platelets. Am J Pathol 1976; 83: 590-632
  • 22 Schaub RG, Rawlings CA. Pulmonary vascular response during various phases of canine heartworm disease: A scanning electron microscopic study. Am J Vet Res 1980; 41: 1082-1089
  • 23 Rawlings CA, Schaub RG, Keith Jr JC. Aspirin reduces pulmonary arteriosclerosis produced by chronic vascular injury. Fed Proc 1984; 43: 976
  • 24 Schaub RG, Rawlings CA, Keith Jr JC. Effect of long-term aspirin treatment of platelet adhesion to chronically damaged canine pulmonary arteries. Thromb Haemostas 1981; 46: 680-683