Prostanoids in the treatment of critical limb ischemia

  • J. D. Gruß
Conference paper


Vascular surgery may claim to be one of the first applications in the endless history of prostanoids. When attending a congress in Japan, I remember seeing a number of young male patients with stages III and IV inoperable arterial occlusive disease being treated with prostaglandin E1 at the University Vascular Surgery Clinic Nagoya (S. Shionoya). Continous intra-arterial therapy was carried out with a timer-controlled roller pump so that the patient received on average 0.2 ng PGE1/kg body weight/min. I have to admit that I had only heard of this compound once during my studies and without any connection with a therapeutic active constituent. The treatment results reported by Shionoya appeared to me so convincing that I was able, with the assistance of the manufacturer Ono and the support of S. Shionoya himself and Flughafen AG Frankfurt to import the compound into Germany during the following months and years in a continuous refrigeration chain, in order to collect initial experience in inoperable stage III and IV arteriosclerosis patients (30, 42). Attempts to publish our first clinical experience with PGE1 in a serious German-language journal failed as a result of their absence of credibility, so that a first communication was only possible in 1978 in the form of a reader’s letter in the Deutsche Medizinische Wochenschrift and then only on the recommendation of my teacher, G. Schettler (19).


Critical Limb Ischemia Arterial Occlusive Disease Peripheral Arterial Occlusive Disease Lumbar Sympathectomy Early Occlusion 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Akaba N (1981) Intra-arterial infusion therapy of prostaglandin E1 with insulin for diabetic gangrene. Surg DiagTreat (Japan) 23: 122Google Scholar
  2. 2.
    Balzer K, Rogatti W, Ruttgerodt K (1989) Therapeutische Wirksamkeit von Prostaglandin E1 -intraarterielle und intravenose PGE1 -Therapie im Stadium III/IV. Therapiewoche 39: 2736–42Google Scholar
  3. 3.
    Bergstrom H, Duner H, von Euler US, Pernow B, Sjovall J (1959) Observations on the effects of infusion of prostaglandin E1 in man. Acta Physiol Scand 45: 145PubMedCrossRefGoogle Scholar
  4. 4.
    Bergstrom S, Ryhage R, Samuelsson B, Sjovall J (1963) Prostaglandins and related factors. The structure of prostaglandin El, F10 and F16. J biol Chem 238: 3555–64Google Scholar
  5. 5.
    Blume J (1987) Klinische Wirksamkeit der intraarteriellen Infusionstherapie mit Prostaglandin E1 im Stadium IIB der arteriellen Verschlußkrankheit. Therapiewoche 37: 4819–23Google Scholar
  6. 6.
    Böhme JIM, Brülisauer M, Härtel U, Bollinger A (1989) Periphere arterielle Verschlußkrankheit im Stadium III und IV- Kontrollierte Zweizentren-Studie zur Wirksamkeit von intraarteriellen Prostaglandin - E1 - Infusionen. Med Welt 40: 1501–3Google Scholar
  7. 7.
    Carlson LA, Ericsson M, Erikson U (1972) Prostaglandin E1 (PGE1) in peripheral arteriographie. Acta Radiol Diagn (Stockholm) 14: 583Google Scholar
  8. 8.
    Carlson LA, Erikson I (1973) Femoral artery infusion of prostaglandin E1 in severe peripheral vascular disease. Lancet 1: 155PubMedCrossRefGoogle Scholar
  9. 9.
    Creutzig A, Creutzig H, Alexander K (1986) Effects of intra-arterial prostaglandin E1 in patients with peripheral arterial occlusive disease. Europ J Clin Invest 16: 480–5PubMedCrossRefGoogle Scholar
  10. 10.
    Creutzig A (1992) Aufhebung von Vasospasmen beim Ergotismus unter i.v. PGE1 Therapie. In: Gruss JD (Hrsg) Angiologie im Bild. Köln, Echo Verlag: 23Google Scholar
  11. 11.
    Creutzig A, Kamin K, Flöge J, Wannske M, Alexander K, Wagner HH (1985) Ergotamin-induzierte periphere Durchblutungsstörungen - ein Fallbericht. Röntgenblätter 38: 193–5.PubMedGoogle Scholar
  12. 12.
    Diehm C, Hübsch-Müller C, Stammler E (1988) Intravenöse Prostaglandin-E1Therapie bei Patienten mit peripherer arterieller Verschlußkrankheit (AVK) im Stadium III - eine doppelblinde plazebokontrollierte Studie. In: Heidrich K, Böhme H, Rogatti W (Hrsg) Prostaglandin E1-Wirkungen und therapeutische Wirksamkeit. Berlin Heidelberg New York, Springer: 133–43Google Scholar
  13. 13.
    Emmons PR, Hampton JR, Harrison MJG, Honour AJ, Mitchel JRA (1967) Effect of prostaglandin E1 on platelet behaviour in vitro and in vivo. Br Med J 2: 468–72PubMedCrossRefGoogle Scholar
  14. 14.
    von Euler US (1935) Über die spezifische blutdrucksenkende Substanz des menschlichen Prostata- und Samenblasensekretes. Klin Wochenschr 14: 1182CrossRefGoogle Scholar
  15. 15.
    von Euler US (1983) History and development of prostaglandins. Gen Pharmac 14: 3CrossRefGoogle Scholar
  16. 16.
    Fantone JC, Kunkel SL, Ward PA, Zuner RB (1981) Suppression of human polymorphonuclear leukocyte function after intervenous infusion of prostaglandin E1 - Prostaglandins Med 2: 195–8Google Scholar
  17. 17.
    Fietze-Fischer B, Gruss JD, Bartels D, Vargas-Montano H, Stritter W(1987) Prostaglandin E1 as an adjuvant therapy in the event of femoro-popliteal and crural saphenous vein in situ bypass surgery. Vasa (Suppl) 17: 23–5Google Scholar
  18. 18.
    Goldblatt MW (1935) Properties of human seminal plasma. J Physiol (London) 84: 208Google Scholar
  19. 19.
    Gruß JD, Kawai S, Karadedos C, Bartels D (1978) Erste Erfahrungen mit der intraarteriellen Langzeitperfusion von Prostaglandin E1 bei fortgeschrittener arterieller Verschlußkrankheit der unteren Extremitäten im Stadium IV, Dtsch Med Wochenschr 41: 1624Google Scholar
  20. 20.
    Gruß JD, Vargas-Montano H, Bartels D, Simmenroth HW, SakuraiT, Schafer G, Fietze-Fischer B (1984) Use of prostaglandins in arterial occlusive diseases. Int Angio Suppl 3: 7Google Scholar
  21. 21.
    Gruß JD (1986) Experiences with PGE1 in patients with phlegmasia cerulea dolens and in ergotism. In: Sinzinger H, Rogatti W (eds) Prostaglandin E1 in Atherosclerosis. Berlin Heidelberg New York, Springer: 99–105Google Scholar
  22. 22.
    Gruß JD, Fietze-Fischer B (1988) Die adjuvante PGE1-Therapie bei femoro-distalen Rekonstruktionen. In: Heidrich H, Rogatti W (Hrsg) Prostaglandin E1 Wirkungen und therapeutische Wirksamkeit. Berlin Heidelberg New York, Springer: 151–9Google Scholar
  23. 23.
    Gruß JD (1989) Experiences with PGE1 in patients with post-operative trash-foot. Vasa (Suppl) 28: 57–60Google Scholar
  24. 24.
    Gruß JD (1991) Adjuvante Therapie bei femoro-distaler Bypasschirurgie. In: Landgrat H (Hrsg) Aktuelle Therapieprinzipien bei der peripheren arteriellen Verschlußkrankheit. Braunschweig, Vieweg: 43–56Google Scholar
  25. 25.
    Gruß JD (1991) Adjuvant intravenous PGE1 treatment after profundaplasty for limb salvage. In: Diehm C, Sinzinger H, Rogatti W (eds) Prostaglandin E1. New Aspects on Pharmacology, Metabolism and Clinical Efficacy. Berlin Heidelberg, Springer: 109–13Google Scholar
  26. 26.
    Gruß JD (1992) Gliedmaßenerhaltung bei peripherer arterieller Verschlußkrankheit im Stadium IV. Der Bay Int 12: 35–8Google Scholar
  27. 27.
    Heidrich H, Breddin HK, Rudotsky G, Scheffler P (1992) Kardiopulmonale Wirkungen von Prostaglandin E1. Med Klin 87: 123–30Google Scholar
  28. 28.
    Heidrich H, Ranft J, Peters A, Rummel S (1987) Früh-und Spätergebnisse nach intravenoser Prostavasm-Therapie bei peripher-arteriellen Durchblutungsstörungen mit Ruheschmerz und Nekrose. Vasa (Suppl) 20: 202Google Scholar
  29. 29.
    Kurzrock L, Lieb CC (1930) Biochemical studies of human semen. II. The action of semen on the human uterus. Proc Soc Exp Biol Med 28: 268Google Scholar
  30. 30.
    Mishima Y (1975) Peripheral vascular disorders. Metabolism and disease. Japan 12: 1727Google Scholar
  31. 31.
    Moncada S, Gryglowski RJ, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663PubMedCrossRefGoogle Scholar
  32. 32.
    Moncada S, Vane JR (1979) Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin. Pharmacol Rev 30: 292Google Scholar
  33. 33.
    Moncada S, Vane JR (1981) Discovery, biological significance and therapeutic potential of prostacyclin. In: Lewis PJ, O’Grady J (eds) Clinical Pharmacology of Prostacyclin. New York. Raven: 1Google Scholar
  34. 34.
    Moncada S (1982) Biological importance of prostacyclin. VII Gaddum Memorial Lecture. Br J Pharmacol 76: 3Google Scholar
  35. 35.
    Ney P, Schrör K (1989) E-type prostaglandins but not doprost inhibit platelet activating factor-induced generation of leukotriene B4 by human polymorphnuclear leukocytes. Br J Pharmacol 96: 186–92PubMedGoogle Scholar
  36. 36.
    Peskar BA, Hesse WH, Rogatti W, Diehm C, Rudofsky G, Schweer H, Scyberth HW (1991) Formations of 13, 14 dihydro-prostaglandin E1 during intravenous infusions of prostaglandin E1 in patients with peripheral arterial occlusive disease. Prostaglandins 41: 225–8PubMedCrossRefGoogle Scholar
  37. 37.
    Rudofsky G (1989) Intravenous prostaglandin E1 in the treatment of venous ulcers -a double blind, placebo-controlled trial. Vasa (Suppl) 28: 39–43Google Scholar
  38. 38.
    Rustin MHA, Kovacs JB, Cooke ED, Dowd PM, Bawcoks SA, Kirby JDT (1984) Experience with PGE1 and PGI2 infusions in patients with systemic sclerosis and Raynaud's phenomenon. Int Angiol 3: 43Google Scholar
  39. 39.
    Sakagushi S, Kusaba, Mischima Y, Kamiya K, Nashimura A, Furukawa K, Shionoya S, Kawashima M, Katsumura T, Sakuma A (1978) A multi-clinical double blind study with PGE1 (a cyclodextrin clathrate) in patients with ischemic ulcer of the extremities. Vasa 7: 263Google Scholar
  40. 40.
    Scheffler P, de la Hamette D, Leiprinz G (1989) Therapeutic efficacy of intravenously applied prostaglandin E1 Vasa 28 (Suppl): 19–25Google Scholar
  41. 41.
    Schrör K (1984) Prostaglandine und verwandte Verbindungen. Stuttgart, Thieme: 101–25Google Scholar
  42. 42.
    Shionoya S, Matsubara J, Hirai M, Kawai S (1976) Dauerperfusion mit Prostaglandin E1 bei peripheren arteriellen Verschlußkrankheiten. Gekachiryo 213: 34Google Scholar
  43. 43.
    Sinzinger H (1986) Inhibition of mitotic and proliferative activity of smooth muscle cells by prostaglandin E1. In: Sinzinger H, Rogatti W (eds) Prostaglandin E1 in Atherosclerosis. Berlin Heidelberg New York, Springer: 39–48Google Scholar
  44. 44.
    Sinzinger H. Fitscha P, Wagner O, Kaliman J, Rogatti W(1986) Prostacyclin E1 decreases activation of arterial smooth-muscle cells, Lancet I: 156–7CrossRefGoogle Scholar
  45. 45.
    Sinzinger H, Fitscha P (1987) Influence of PGE1 on invivo accumulation of radiolabeled platelets and LDL on human arteries. Vasa 17 (Suppl): 5–10Google Scholar
  46. 46.
    Sinzinger H, Virgolini J, Lupatelli G, Hanyai M (1991) PGE1 and 13, 14 dihydro PGE1 increase low-density lipoprotein receptors and improve arterial wall lipid metabolism. In: Diehm C, Sinzinger H, Rogatti W (eds) Prostaglandin E1. Berlin Heidelberg New York, Springer: 39–48Google Scholar
  47. 47.
    Spiecker M, Buereke M, Darius H, Meyer J (1992) Antithrombotische und hämodynamische Effekte der Prostacyclin-Analoga Hoprest und Taprosten in vivo. Perfusion 11: 326–30Google Scholar
  48. 48.
    Trübestein G, Ludwig M, Diehm C, Gruß JD, Horsch S (1987) Prostaglandin E1 bei arterieller Verschlußkrankheit im Stadium III und IV. Dtsch Med Wochenschr 112: 995CrossRefGoogle Scholar
  49. 49.
    Trübestein G, v. Bary S, Breddin K, Diehm C, Gruß JD, Heidrich H, Horsch S, Kriessmann A, Maass U, Marin N, Scheifler P (1989) Intravenous prostaglandin E1 versus pentoxifylline therapy in chronic arterial occlusive disease -a controlled randomized multicentre study. Vasa (Suppl) 28: 44–49Google Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt 1995

Authors and Affiliations

  • J. D. Gruß
    • 1
  1. 1.Dept. of Vascular SurgeryKurhess DiakonissenhausKasselGermany

Personalised recommendations