Enhancement of Platelet Sensitivity to ADP-Aggregation by Isometric Exercise in Arteriosclerotic Patients and its Prevention

Summary

A new method for assessment of platelet sensitivity to ADP-aggregation was devised. Its reproducibility and the correlations between the values obtained by this method, the optical density (O. D.) method, and the screen filtration pressure (SFP) method were assessed. In summary, this method may be said to have three main points:

1. It can be performed without centrifugation, avoiding mechanical stress to platelets, using only 0.8 ml. of blood and inexpensive equipment.

2. It may reflect different aspects of platelet function from the O. D. method and the SFP method, despite the positive significant correlations between the values obtained by these three methods.

3. It was proved to be highly reproducible and is thought to be useful clinically.

By using this method, the effect of sustained isometric exercise by handgripping on platelet aggregability was assessed in coronary sclerotic and cerebral arteriosclerotic patients on placebo and EG-626, a newly synthesized cyclic AMP phosphodiesterase inhibitor. On placebo, an enhancement of platelet sensitivity was observed after isometric exercise in coronary and cerebral arteriosclerotic patients but not in healthy control subjects. The enhancement was prevented by pretreatment of EG-626, administered orally 1.5 hours prior to exercise.

• References

• 1 Born G. V. R. Quantitative investigation into aggregation of blood platelets. Journal of Physiology 1962; 162: 67
• 2 Emmons P. R, Mitchell J. R. A. Postoperative changes in platelet-clumping activity. Lancet 1965; 1: 71
• 3 Haft J. I, Levites R. Exercise-induced stress and platelet aggregation. Circulation, 49-50, Supplement 1974; 3: 288
• 4 Hidaka H, Asano T, Shibuya M, Shimamoto T. Cyclic GMP phosphodiesterase of human blood platelets and its inhibitors. Thrombosis et Diathesis Haemorrhagica, Supplement 1974; 60: 321
• 5 Inceman S, Tangun Y. A simple test for the evaluation of platelet coagulant activity. Journal of Laboratory and Clinical Medicine 1969; 74: 174.
• 6 Lüscher E. F, Massini P. On the mechanism by which cell contact induces the release reaction of blood platelets; the effect of cationic polymers. Thrombosis et Diathesis Haemorrhagica 1972; 27: 121
• 7 Nutter O. D, Schlant R. C, Hurst J. W. Isometric exercise and the cardiovascular system. Modern Concept of Cardiovascular Disease 1972; 41: 11
• 8 O’Brien J. R. Platelet aggregation. Part 2. Some results from a new method of study. Journal of Clinical Pathology 1962; 15: 452
• 9 O’Brien J. R, Heywood J. B, Heady J. A. The quantitation of platelet aggregation induced by four compounds: a study in relation to myocardial infarction. Thrombosis et Diathesis Haemorrha-gica 1966; 16: 752
• 10 O’Brien J. R, Woodhouse M. A. Platelets: their size, shape, and stickiness in vitro: de-granulation and propinquity. Experimental Biology and Medicine 1968; 3: 90
• 11 Salzman E. W, Neri L. Cyclic 3’, 5’-adenosine monophosphate in human blood platelets. Nature 1969; 224: 609
• 12 Salzman E. W, Rubino E. B, Sims R. V. Cyclic 3’, 5’-adenosine monophosphate in human blood platelets. III. The role of cyclic AMP in platelet aggregation. Series Haemotologica 1970; III: 100
• 13 Salzman E. W. Cyclic AMP and platelet function. New England Journal of Medicine 1972; a 286: 358
• 14 Salzman E. W, Kensler P. C, Levine L. Cyclic 3’, 5’-adenosine monophosphate in human blood platelets. IV. Regulatory role of the cyclic AMP in platelet function. Annals of New York Academy of Sciences 1972; b 201: 61
• 15 Salzman E. W. Prostaglandins, cyclic AMP, and platelet function. Thrombosis et Diathesis Haemorrhagica, Supplement 1974; 60: 311
• 16 Sano T, Boxer M. G. J, Boxer L. A, Yokoyama M. Platelet sensitivity to aggregation in normal and diseased groups; a method for assessment of platelet aggregability. Thrombosis et Diathesis Haemorrhagica 1971; 25: 524
• 17 Shimamoto T, Numano F, Yamazaki H, Murase H. Cyclic AMP phosphodiesterase (CAMPPDE) inhibitors in the treatment of senile mental detrioration cerebellar ataxia and thrombotic and atherosclerotic disorders. In: Frontiers of Internal Medicine, 1974. Proceedings of the Twelfth International Congress of Internal Medicine, Tel Aviv, 1974, Karger, Basel 1975; p. 110
• 18 Swank R. L. Alteration of blood on storage: measurement of adhesiveness of ‘ageing’ platelets and leukocytes and their removal by filtration. New England Journal of Medicine 1961; 265: 728
• 19 World Health Organization Expert Committee on Arterial Hypertension, Ischaemic Heart Disease. Arterial hypertension and ischaemic heart disease: preventive aspects. World Health Organization Technical Report Series 1962; 231: 1
• 20 Yamakido M, Oishi N, Yokoyama M. Studies on ADP-induced platelet aggregation in normal and diseased groups. Hawaii Medical Journal 1970; 29: 446
• 21 Yamazaki H, Sano T, Odakura T, Takeuchi K, Shimamoto T. Electocardiographic and hematological changes by exercise test in coronary patients and pyridinolcarbamate pretreatment: a double blind crossover trial. American Heart Journal 1970; a 79: 640
• 22 Yamazaki H, Kobayashi I, Shimamoto T. Enhancement of ADP-induced platelet aggregation by exercise test in coronary patients and its prevention by pyridinolcarbamate. Thrombosis et Diathesis Haemorrhagica 1970; b 24: 438
• 23 Yamazaki H, Sano T, Shimamoto T, Mashimo N, Takahashi T, Shimamoto T. Platelet function in thromboembolic disorders. Thrombosis et Diathesis Haemorrhagica, Supplement 1974; 60: 213
• 24 Zucker M. Proteolytic inhibitors, contact and other variables in the release reaction of human platelets. Thrombosis et Diathesis Haemorrhagica 1972; 28: 393