Skip to main content
Log in

Prolonged infusion of prostacyclin in patients with advanced stages of peripheral vascular disease: A placebo-controlled cross-over study

  • Originalien
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

Twelve patients (age 33–77 years, mean age 68.4 years) with peripheral vascular disease (PVD) stage III–IV received continuous intravenous infusions of 5 ng prostacyclin (PGI2)/kg/min and physiological saline for 7 days. The administration was randomized and double-blind with an interval of 7 days between the infusions. During PGI2 infusion systolic blood pressure fell significantly from 147.8±4.8 mm Hg to 140.6±4.0 mm Hg (P<0.01) and returned to 144.5±4.9 mm Hg post infusion. Transcutaneous p O2 (tcp O2 ) measured on the instep of the affected limb increased significantly by 8.9±3.8 Torr during PGI2 infusion and remained elevated during the subsequent week. A significant reduction of pain was observed from the 5th day of PGI2 infusion, lasting for at least the following observation period. Platelet cAMP increased from 18.8±1.5 pmol/108 platelets to 24.7±1.6 pmol/108 platelets on the 3rd day of PGI2 infusion (P<0.01). Spontaneous platelet aggregation was also significantly reduced during PGI2 infusion. However, 7 days after the infusion thromboxane B2 (TXB2) in plasma and spontaneous platelet aggregation significantly increased in comparison with the preinfusion values, indicating a rebound phenomenon. The clinical outcome was favorable in 9 of 12 patients, was unchanged in two patients, while progressing to limb amputation in one patient.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

TXA2 :

Thromboxane A2

PGI2 :

Prostacyclin

PVD:

Peripheral Vascular Disease

tcpO2 :

transcutaneous pO2

VAS:

Visual Analog Scale

PAT III:

Platelet Aggregation Test III by Breddin

HDL:

high density lipoprotein

AT III:

antithrombin III

SFMC:

Soluble fibrinogen-fibrin monomer complexes

PAR:

platelet aggregation ratio

References

  • Araki H, Lefer AM (1980) Role of prostacyclin in the preservation of ischemic myocardial tissue in the perfused cat heart. Circ Res 47:757–763

    PubMed  Google Scholar 

  • Belch JJF, McArdle B, Pollock JG, Forbes CD, McKay A, Leiberman P, Lowe GDO, Prentice CRM (1983) Epoprostenol (prostacyclin) and severe arterial disease. A doubleblind trial. Lancet I:315–317

    Google Scholar 

  • Blättler W, Furrer K, Schriber K, Kofmehl R, Massini C (1981) Platelet proteins during and after prostacyclin therapy for lower limb ischaemia — suggestion of a rebound platelet activation. Vasa 10:261–263

    PubMed  Google Scholar 

  • Breddin K, Grun H, Krzywanek HJ, Schremmer WP (1976) On the measurement of spontaneous platelet aggregation: the platelet aggregation test III. Method and first clinical results. Thromb Haemostas 35:669–691

    Google Scholar 

  • Bunting S, Moncada S, Vane JR (1983) The prostacyclin-thromboxane A2 balance: Pathophysiological and therapeutic implications. Br Med Bull 39:271–277

    PubMed  Google Scholar 

  • Dembinska-Kiec A, Kosta-Trabka E, Zmuda A, Byrska-Danek A, Bieron K, Grodzinska L, Kedzior A, Zelazny T (1982) Effect of prostacyclin (PGI2) on platelets and fibrinolytic activity in patients with arteriosclerosis obliterans. Pharmacol Res Commun 14:485–498

    PubMed  Google Scholar 

  • FitzGerald GA, Brash AR, Falardeau P, Oates JA (1981) Estimated rate of prostacyclin secretion into the circulation of normal man. J Clin Invest 68:1272–1276

    PubMed  Google Scholar 

  • FitzGerald GA, Smith B, Pedersen AK, Brash AR (1984) Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. N Engl J Med 310:1065–1068

    PubMed  Google Scholar 

  • Gilman AG (1970) Protein binding assay for adenosine 3-5-cyclic monophosphate. Proc Natl Acad Sci (USA) 67:305–312

    PubMed  Google Scholar 

  • Hafter R, Graeff H (1976) Estimation of soluble fibrin monomer complexes by agarose gel filtration. In: Davidson JF, Samama MM, Desnoyers PC (eds) Progress in Chemical Fibrinolysis and Thrombolysis. Vol 2. Raven Press, New York, pp 137–149

    Google Scholar 

  • Hamberg M, Svensson J, Samuelsson B (1975) Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci (USA) 72:2994–2998

    PubMed  Google Scholar 

  • Hossmann V, Heinen A, Auel H, FitzGerald GA (1981) A randomized, placebo controlled trial of prostacyclin (PGI2) in peripheral arterial disease. Thromb Res 22:481–490

    PubMed  Google Scholar 

  • Kovacs IB, O'Grady J (1982) Prostacyclin increases filterability of normal fresh and stored human red blood cells. Br J Clin Pharmacol 13:298P

  • Machin SJ, Chamone DAF, Defreyn G, Vermylen J (1981) The effect of clinical prostacyclin infusions in advanced arterial disease on platelet function and plasma 6-keto PGF levels. Br J Haematol 47:413–422

    PubMed  Google Scholar 

  • Moncada S, Gryglewski R, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665

    PubMed  Google Scholar 

  • Olsson AG, Nilsson E (1981) The effect of intravenous prostacyclin on resting pains and healing of ischaemic ulcers in peripheral artery disease. Prostaglandins Med 6:329–339

    PubMed  Google Scholar 

  • Pardy BJ, Lewis JD, Eastcott HHG (1980) Preliminary experience with prostaglandins E1 and I2 in peripheral vascular disease. Surgery 88:826–832

    PubMed  Google Scholar 

  • Peskar BA, Anhut H, Kröner EE, Peskar BM (1978) Development, specificity and some applications of radioimmunoassays for prostaglandins and related compounds. In: Tillement JP (ed) Advances in pharmacology and therapeutics, Vol 7. Pergamon Press, Oxford New York, pp 275–286

    Google Scholar 

  • Ritter JM, Blair IA, Barrow SE, Dollery CT (1983) Release of prostacyclin in vivo and its role in man. Lancet I:317–319

    Google Scholar 

  • Schrör K, Ohlendorf R, Darius H (1981) Beneficial effects of a new carbacyclin derivative, ZK 36374, in acute myocardial ischemia. J Pharmacol Exp Ther 219:243–249

    PubMed  Google Scholar 

  • Sinzinger H, Silberbauer K, Horsch AK, Gall A (1981) Decreased sensitivity of human platelets to PGI2 during longterm intraarterial prostacyclin infusion in patients with peripheral vascular disease — a rebound phenomenon? Prostaglandins 21:49–51

    PubMed  Google Scholar 

  • Szczeklik A, Skawinski S, Gluszko P, Nizankowski R, Szczeklik J, Gryglewski RJ (1979) Successful therapy of advanced arteriosclerosis obliterans with prostacyclin Lancet I:1111–1114

    Google Scholar 

  • Szczeklik A, Gryglewski RJ, Nizankowski R, Skawinski S, Gluszko P, Korbut R (1980) Prostacyclin therapy in peripheral arterial disease. Thromb Res 19:191–199

    PubMed  Google Scholar 

  • Thiemermann C, Steinhagen-Thiessen E, Schrör K (1984) Inhibition of oxygen-centered free radical formation by the stable prostacyclin-mimetic Iloprost (ZK 36374) in acute myocardial ischemia. J Cardiovasc Pharmacol 6:365–366

    PubMed  Google Scholar 

  • Working Group Report on Red Cell Deformability. Methods and terminology. Second European Conference on Clinical Haemorheology, London, 29th September, 1981. Russell Wilks Associates, London

  • Wu KK, Hoak JC (1974) A new method for the quantitative detection of platelet aggregates in patients with arterial insufficiency. Lancet II:924–926

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

For Professor Dr. W. Kaufmann on his 60th Geburtstag

Supported by the Landesamt für Wissenschaft und Forschung, NRW

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hossmann, V., Auel, H., Rücker, W. et al. Prolonged infusion of prostacyclin in patients with advanced stages of peripheral vascular disease: A placebo-controlled cross-over study. Klin Wochenschr 62, 1108–1114 (1984). https://doi.org/10.1007/BF01782467

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01782467

Key words

Navigation