Repeated Exercise Induces Release of Soluble P-Selectin in Patients with Intermittent Claudication

Summary

Controversy exists as to whether exercise in patients with intermittent claudication causes a harmful biochemical effect associated with an ischaemia-reperfusion injury of skeletal muscle. We report on exercise-induced changes in neutrophil activation, soluble P-selectin and von Willebrand factor in 34 patients with intermittent claudication and 12 matched controls.

Von Willebrand factor (vWF) showed a cyclical pattern of response to exercise in control subjects (rising from 103 ± 8 to 119 ± 7 U/dl); claudicants did not show this pattern but had higher levels of vWF throughout (p <0.03). There was no consistent pattern of response in neutrophil hydrogen peroxide production to exercise in either claudicants or control subjects. Soluble P-selectin levels increased after exercise, but this only reached statistical significance after repeated exercise in claudicants (rising from 320 ± 28 to 357 ± 28 ng/ml). This rise in soluble P-selectin after exercise may indicate progressive platelet activation which may contribute to the excess cardiovascular mortality that claudicants are prone to.

• References

• 1 Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham study. J Am Geriatr Soc 1985; 33: 13-18
• 2 Jonason T, Ringqvist I. Mortality and morbidity in patients with intermittent claudication in relation to the location of the occlusive atherosclerosis in the leg. Angiology 1985; 36: 310-314
• 3 Jelnes R, Gaardsting O, Hougard JensenK. Fate in intermittent claudication: outcome and risk factors. Br Med J 1986; 293: 1137-1140
• 4 O’Riordain DS, O’Donnell JA. Realistic expectations for the patient with intermittent claudication. Br J Surg 1991; 78: 861-863
• 5 Reunanen A, Takkunen H, Aromaa A. Prevalence of intermittent claudication and its effect on mortality. Acta Med Scand 1982; 211: 249-256
• 6 Bainton D, Sweetnam P, Baker I, Elwood P. Peripheral vascular disease: consequence for survival and association with risk factors in the Speedwell prospective heart disease study. Br Heart J 1994; 72: 128-132
• 7 Dormandy JA. Natural history of intermittent claudication. Hospital Update 1991; 17: 314-320
• 8 Hiatt WR, Regensteiner JG, Hargarten ME, Wolfel EE, Brass EP. Benefit of exercise conditioning for patients with peripheral arterial disease. Circulation 1990; 81: 602-609
• 9 Tsang GMK, Sanghera K, Gosling P. et al. Pharmacological reduction of the systemically damaging effects of local ischaemia. Eur J Vase Surg 1994; 08: 205-208
• 10 Hickey NC, Gosling P, Baar S, Shearman CP, Simms MH. Effect of surgery on the systemic inflammatory response to intermittent claudication. Br J Surg 1990; 77: 1121-1124
• 11 Shearman CP, Gosling P, Gwynn BR, Simms MH. Systemic effects associated with intermittent claudication. A model to study biochemical aspects of vascular disease?. Eur J Vase Surg 1988; 02: 401-404
• 12 Wagner DD. The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost 1993; 70: 01-05
• 13 McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF. GMP-140, a platelet a-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 1989; 84: 92-99
• 14 Kostelijk EH, Fijnheer R, Nieuwenhuis HK, Gouwerok CWN, de KorteD. Soluble P-selectin as parameter for platelet activation during storage. Thromb Haemost 1996; 76: 1086-1089
• 15 Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulation. J Immunol 1983; 130: 1910-1917
• 16 Short PE, Williams CE, Picken AM, Hill FGH. Factor VIII related antigen: an improved immunoassay. Med Lab Sci 1982; 39: 351-355
• 17 McCarthy DA, Perry JD, Melsom RD, Dale MM. Leucocytosis induced by exercise. Br Med J 1987; 295: 636
• 18 Allsop P, Peters AM, Amot RN. et al. Intrasplenic blood cell kinetics in man before and after brief maximal exercise. Clin Science 1992; 83: 47-54
• 19 Lowe GDO, Fowkes FGR, Dawes J, Donnan PT, Lennie SE, Housley E. Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study. Circulation 1993; 87: 1915-1920
• 20 Blann AD, Dobrotova M, Kubisz P, McCollum CN. Von Willebrand factor, soluble P-selectin, tissue plasminogen activator and plasminogen activator inhibitor in atherosclerosis. Thromb Haemost 1995; 74: 626-630
• 21 Cella G, Zahavi J, De HaasHA, Kakkar VV. β-Thromboglobulin, platelet production time and platelet function in vascular disease. Brit J Haematol 1979; 43: 127-136
• 22 Fitzgerald GA, Smith B, Pedersen AK, Brash AR. Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N Engl J Med 1984; 310: 1065-1068
• 23 Dormandy JA, Hoare E, Khattab AH, Arrowsmith DE, Dormandy TL. Prognostic significance of rheological and biochemical findings in patients with intermittent claudication. Br Med J 1973; 04: 581-583
• 24 Fowkes FGR, Lowe GDO, Housley E. et al. Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease. Lancet 1993; 342: 84-86
• 25 Stuart J, George AJ, Davies AJ, Aukland A, Hurlow RA. Haematological stress syndrome in atherosclerosis. J Clin Pathol 1981; 34: 464-467
• 26 Khaira HS, Nash GB, Bahra PS. et al. Thromboxane and neutrophil changes following intermittent claudication suggest ischaemia-reperfusion injury. Eur J Vase Endovasc Surg 1995; 10: 31-35
• 27 Edwards AT, Blann AD, Suarez-Mendez VJ, Lardi AM, McCollum CN. Systemic responses in patients with intermittent claudication after treadmill exercise. Br J Surg 1994; 81: 1738-1741
• 28 Khaira HS, Maxwell SRJ, Shearman CP. Antioxidant consumption during exercise in intermittent claudication. Br J Surg 1995; 82: 1660-1662
• 29 Wall RT, Counts RB, Harker LA, Striker GE. Binding and release of Factor III/von Willebrand’s factor by human endothelail cells. Brit J Haematol 1980; 46: 287-298
• 30 Blann AD, Seigneur M, Adams RA, McCollum CN. Neutrophil elastase, von Willebrand factor, soluble thrombomodulin and percutaneous oxygen in peripheral atherosclerosis. Eur J Vase Endovasc Surg 1996; 12: 218-222
• 31 Ikeda H, Takajo Y, Ichiki K. et al. Increased soluble form of P-selectin in patients with unstable angina. Circulation 1995; 92: 1693-1696
• 32 Pan YZ, Wu BM, Hong XS. The clinical significance of platelet activation during exercise-induced myocardial ischaemia. Chung Hua Nei Ko Tsa Chih 1994; 33: 106-108
• 33 Hickman P, Hill A, McLaren M, Belch JJF, McCollum PT. Exercise induces activation in claudicants but not in age-matched controls. Br J Surg 1993; 80: 1472 (abstract).
• 34 Eyers PS, Lardi A, Wood JA, McCollum CN. Exercise primes neutrophils in patients with intermittent claudication. Br J Surg 1994; 81: 1799-1826 (abstract)
• 35 Perkins JMT, Collin J, Creasy TS, Fletcher EWL, Morris PJ. Exercise training versus angioplasty for stable claudication. Long and medium term results of a prospective, randomised trial. Eur J Vase Endovasc Surg 1996; 11: 409-413