Advertisement

Clinical Use of Prostacyclin in Vascular Disease

  • R. J. Gryglewski
  • A. Szczeklik
  • E. Kostka-Trabka
  • H. Zygulska-Mach
Part of the NATO Advanced Science Institutes Series book series (NSSA, volume 54)

Abstract

Two main biological effects of prostacyclin, i.e., its effect on platelets and vasodilation, were already observed during the first intravenous administration of prostacyclin to man [5, 25] and were confirmed in later studies [7, 14]. The action of pros-tacyclin on platelets is manifested in its anti-aggregatory and disaggregatory properties [5, 18, 26]. The former are seen as a marked inhibition of ADP- or collagen-induced platelet aggregation in PRP, the latter as dispersion of both circulating platelet aggregates and platelet thrombi that have been formed on a collagen surface [18]. These effects are observed within first 15–45 min of infusion of prostacyclin (PGI2). However, after 24 hr, and usually after 72 hr of administration of PGI2, an unexpected activation of platelets is observed in patients who were treated with prostacyclin (2–5 ng/kg/min i.v.) (Fig. 1). Recently, Sinzinger et al. [16]. found in vivo a similar activation of platelets in patients with peripheral arterial disease who were treated with PGI2 (5 ng/kg/min) for a period of 8 days. A sudden decrease in platelet sensitivity to PGI2, increased β-thromboglobulin level in blood, increased circulating platelet factor 4 (PF4) were observed as soon as 24 hr after beginning of the therapy. This “rebound effect” of PGI2 on platelets is of an unknown mechanism but exhaustion of the platelet adenylate-cyclase system is one of possible explanations.

Keywords

Central Retinal Vein Occlusion Stroke Volume Index Pulmonary Artery Hypertension Retinal Blood Vessel Arteriosclerosis Obliterans 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. W. Aiken, R. R. Gorman, and R. J. Shebuski, Prostacyclin prevents blockage of partially obstructed coronary arteries, in: “Prostacyclin” ( J. R. Vane and S. Bergström, eds.), Raven Press, New York (1979).Google Scholar
  2. 2.
    J. M. Armstrong, D. Chapple, D. J. Dusting, R. Hughes, S. Moncada, and J. R. Vane, Cardiovascular actions of prostacyclin in chloralose anaesthetized dogs, Br. J. Pharmacol., 61: 36P (1977).Google Scholar
  3. 3.
    H. J. Dargie and P. J. Lewis, Effect of prostacyclin on angina at rest, in: “Clinical Pharmacology of Prostacyclin” ( P. J. Lewis and J. O’Grady, eds.), Raven Press, New York (1981).Google Scholar
  4. 4.
    T. M. Fitzpatrick, I. Alter, E. J. Corey, P. W. Ramwell, J. C. Rose, and P. A. Kot, Cardiovascular responses to PGI2 (Prostacyclin) in the dog, Circ. Res., 42: 192 (1978).Google Scholar
  5. 5.
    R. J. Gryglewski, A. Szczeklik, and R. Nizankowski, Anti-platelet action of intravenous infusion of prostacyclin in man, Thrombos. Res., 13: 153 (1978).Google Scholar
  6. 6.
    H. B. Hechturan, T. Utsunomiya, A. M. Vegas, G. A. Grindlinger, G. A. McLaughlin, M. M. Krausz, and D. Shepro, Prostaglandin mediation of pulmonary fibrinolytic activity, in: Symposium A. Einstein Coll. of Med., Raven Press, New York (in press).Google Scholar
  7. 7.
    V. Hossman, G. A. FitzGerald, A. Heinen, and H. Auel, Effect of prostacyclin on haemorrheology and haemostasis in obliterative arterial disease, in: “Clinical Pharmacology of Prostacyclin” ( P. J. Lewis and J. O’Grady, eds.), Raven Press, New York (1981).Google Scholar
  8. 8.
    P. J. Kadovitz, B. M. Chapnick, L. P. Feigen, A. L. Hyman, P. K. Nelson, and E. W. Spannhake, Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin PGI2, J. Appl. Physiol.: Resp. Environm. Exerc. Physiol., 45 /3: 403 (1978).Google Scholar
  9. 9.
    A. M. Lefer and E. F. Smith III, Protective action of prostacyclin in myocardial ischemia and trauma, in: “Prostacylin” ( J. R. Vane and S. Bergström, eds.), Raven Press, New York (1979).Google Scholar
  10. 10.
    S. J. Machin, G. Defreyn, D. A. F. Chamone, and J. Vermylen, Clinical infusions of prostacylin in advanced arterial disease, in: “Clinical Pharmacology of Prostacyclin” ( P. J. Lewis and J. O’Grady, eds.), Raven Press, New York (1981).Google Scholar
  11. 11.
    A. Masseri, Pathogenetic mechanism of angina pectoris: expanding views, Br. Heart J., 43: 648 (1980).CrossRefGoogle Scholar
  12. 12.
    R. N. McAlpin, Relation of coronary arterial spasm to site of organic stenosis, Am. J. Cardiol., 46: 143 (1980).CrossRefGoogle Scholar
  13. 13.
    J. Mehta, P. Mehta, and G. J. Pepine, Platelet aggregation in aortic and coronary venous blood in patients with and without coronary disease, 3: Role of tachycardial stress and practolol. Circulation, 58: 881 (1978).PubMedCrossRefGoogle Scholar
  14. 14.
    J. O’Grady, S. Warrington, M. J. Moti, S. Bunting, R. Flower, A. S. E. Higgs, E. A. Fowle, and S. Moncada, Effects of intravenous prostacyclin infusions in healthy volunteers - some preliminary observations, in: “Prostacyclin” ( J. R. Vane and S. Bergström, eds.), Raven Press, New York (1979).Google Scholar
  15. 15.
    Report on the Joint Int. Soc. and Fed. of Cardiology/WHO Task Force on Standardization of Clinical Nomenclature: Nomenclature and Criteria for Diagnosis of Ischemic Heart Disease, Circulation, 59: 697 (1979).Google Scholar
  16. 16.
    H. Sinzinger, K. Silberbauer, A. K. Harsch, and A. Gall, Decreased sensitivity of human platelets to PGI2 during longterm intraarterial prostacyclin infusion in patients with peripheral vascular disease - a rebound phenomenon, Prostaglandins, 21: 49 (1981).PubMedGoogle Scholar
  17. 17.
    E. W. Spannhake, B. W. Chapnick, L. P. Faigen, P. K. Nelson, A. L. Hyman, M. K. Carter, and P. J. Kadovitz, Pulmonary and systemic vasodilator effects of prostacyclin, Fed. Proc., 37: 731 (1978).Google Scholar
  18. 18.
    A. Szczeklik and R. J. Gryglewski, Actions of prostacyclin in man, in: “Prostacyclin” ( J. R. Vane and S. Bergström, eds.), Raven Press, New York (1979).Google Scholar
  19. 19.
    A. Szczeklik and R. J. Gryglewski, Low-density lipoproteins (LDL) are carriers for lipid peroxides and invalidate prostacyclin (PGI2) biosynthesis in arteries, Artery, 7: 488 (1980).PubMedGoogle Scholar
  20. 20.
    A. Szczeklik and R. J. Gryglewski, Treatment of vascular di-ease with prostacyclin, in: “Clinical Pharmacology of Prostacyclin” ( J. P. Lewis and J. O’Grady, eds.), Raven Press, New York (1980).Google Scholar
  21. 21.
    R. Nizankowski, Hemodynamic in: “Adv. Prostagl. Thrombox. R. Nizankowski, Hemodyanamic in man, Br. Heart J., 44: 254Google Scholar
  22. 22.
    A. Szczeklik, R. J. Gryglewski, E. Kostka-Trabka, R. Nizankowski, S. Skawinski, 0. Billewicz, P. Gluszko, J. Szczeklik, L. Grodzinska, A. Dembinska-Kiee, K. Bieron, and E. Telesz, Prostacyclin in treatment of peripheral vascular disease of lower extremities [in Polish], Przegl. Lek., 37: 659 (1980).PubMedGoogle Scholar
  23. 23.
    A. Szczeklik, R. J. Gryglewski, J. Musial, L. Grodzinska, M. Serwonska, and E. Marcinkiewicz, Thromboxane generation and platelet aggregation in survivals of myocardial infarction, Thrombos. Haemostas., 40: 66 (1978).Google Scholar
  24. 24.
    A. Szczeklik, R. J. Gryglewski, E. Nizankowska, R. Niankowski, and J. Musial, Pulmonary and anti-platelet effects of intravenous and inhaled prostacyclin in man, Prostaglandins, 16: 651 (1978).Google Scholar
  25. 25.
    A. Szczeklik, R. J. Gryglewski, R. Nizankowski, J. Musial, R. Pieton, and J. Mruk, Circulatory and anti-platelet effects of intravenous prostacyclin in healthy mean, Pharmacol. Res. Commun., 10: 545 (1978).Google Scholar
  26. 26.
    A. Szczeklik, R. J. Gryglewski, R. Nizankowski, S. Skawiriski, and P. Gluszko, Prostacyclin therapy of peripheral vascular disease, Thrombos. Res., 19: 191 (1980).Google Scholar
  27. 27.
    A. Szczeklik, R. Nizankowski, S. Skawiriski, J. Szczeklik, P. Gluszko, and R. J. Gryglewski, Successful therapy of advanced arteriosclerosis obliterans with prostacyclin, Lancet, 1: 1111 (1979).PubMedCrossRefGoogle Scholar
  28. 28.
    A. Szczeklik, R. Piptori, J. Sieradzki, and R. Nizankowski, The effects of prostacyclin on glycemia and insulin release in man, Prostaglandins, 19: 959 (1980).PubMedGoogle Scholar
  29. 29.
    A. Szczeklik, J. Szczeklik, R. Nizankowski, and P. Gluszko, Prostacyclin for unstable angina, N. Engl. J. Med., 303: 881 (1980).PubMedGoogle Scholar
  30. 30.
    J. Szczeklik, J. S. Dubiel, M. Mysik, R. Król, and T. Horzela, Effedts of prostaglandin E1 on pulmonary circulation in patients with pulmonary hypertension, Br. Heart J., 40: 1397 (1978).PubMedCrossRefGoogle Scholar
  31. 31.
    J. Szczeklik, A. Szczeklik, and effects of prostacyclin in man, Res., 7: 687 (1980).Google Scholar
  32. 32.
    J. Szczeklik, A. Szczeklik, and changes induced by prostacyclin (1980).Google Scholar
  33. 33.
    J. Szczeklik, A. Szczeklik, and R. Nizankowski, Prostacyclin for pulmonary hypertension, Lancet, 2: 1076 (1980).PubMedCrossRefGoogle Scholar
  34. 34.
    J. E. Thompson and W. V. Garrett, Peripheral artery surgery, N. Engl. J. Med., 302: 491 (1979).CrossRefGoogle Scholar
  35. 35.
    W. D. Watkins, M. P. Peterson, R. K. Brone, and L. Levine, Prostacyclin and prostaglandin E1 for severe pulmonary artery hypertension, Lancet, 1: 1083 (1980).PubMedCrossRefGoogle Scholar
  36. 36.
    H. Źgulska-Mach, E. Kostka-Trabka, A Niton, and R. Gryglewski, Prostacyclin in central retinal vein occlusion, Lancet, 2: 1075 (1980).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • R. J. Gryglewski
    • 1
  • A. Szczeklik
    • 1
  • E. Kostka-Trabka
    • 1
  • H. Zygulska-Mach
    • 1
  1. 1.N. Copernicus Academy of MedicineKrakówPoland

Personalised recommendations