Skip to main content
Log in

Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease

Results of a double-blind placebo-controlled study

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

The effects of an infusion of pentoxifylline 1 g as an inhibitor of free radical generation have been determined in a double-blind placebo-controlled study. Leucocyte-derived free radical generation (by the superoxide dismutase-inhibitable reduction of ferricytochrome), the release of reactive oxygen metabolites (as plasma oxidant activity), unfractionated leucocyte and erythrocyte filterability rates (using a constant-flow positive-pressure system), plasma viscosity, and plasma fibrinogen concentration have been measured in two matched groups of 10 patients with Stage II peripheral vascular disease, before and after treatment. Transcutaneous oxygen pressure (PtcO2) during treadmill exercise to stress leg circulation was also measured.

Leucocyte-derived free radicals were generated during peripheral ischaemia. Pentoxifylline inhibited their generation, blocked the release of reactive oxygen metabolites, and reduced impairment of the filterability rate of unfractionated leucocytes.

The improvements were accompanied by significant shortening of the half-time of recovery of transcutaneous oxygen pressure, indicating that ischaemic damage had been contained.

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

References

  1. Baumann JC (1983) New prospects for the conservative management of peripheral arterial disease: clinical investigations with pentoxifylline (Trental 400). Pharmatherapeutica 3 [Suppl 1]: 30–41

    Google Scholar 

  2. Kellner H (1983) Treatment of chronic arterial circulatory disorders: double-blind trial with pentoxifylline (Trental 400). Pharmatherapeutica 3 [Suppl 1]: 67–73

    Google Scholar 

  3. Di Perri T, Carandente O, Vittoria A, Guerrini M, Messa GL (1984) Studies of the clinical pharmacology and therapeutic efficacy of penoxifylline in peripheral obstructive arterial disease. Angiology 35: 427–435

    Google Scholar 

  4. Strano A, Davo G, Avellone G, Novo S, Pinto A (1984) Double-blind crossover study of the clinical efficacy and the hemorheological effects of pentoxifylline in patients with occlusive arterial disease of the lower limbs. Angiology 35: 439–446

    Google Scholar 

  5. Angelides NS (1986) Continuous infusion treatment with pentoxifylline in patients with severe peripheral vascular occlusive disease. Angiology 37: 555–564

    Google Scholar 

  6. Ohshima N, Sato M (1981) Effect of pentoxifylline on microvascular blood flow velocity. Angiology 32: 752–763

    Google Scholar 

  7. Schultheiss R, Leuwer R, Leniger-Follert E, Wassmann H, Wullenweber R (1987) Tissue PO2 of human brain cortex: method, basic results and effects of pentoxifylline. Angiology 38: 221–225

    Google Scholar 

  8. Angelkort B, Kiesewetter H (1981) Influence of risk factors and coagulation phenomena on the fluidity of blood in chronic arterial occlusive disease. Scand J Clin Lab Invest 41: 185–188

    Google Scholar 

  9. Angelkort B, Spurk P, Habbaba A, Mahder M (1985) Blood flow properties and walking performance in chronic arterial occlusive disease. Angiology 36: 285–292

    Google Scholar 

  10. Angelkort B, Maurin N, Boateng K (1979) Influence of pentoxifylline on erythrocyte deformability in peripheral occlusive arterial disease. Curr Med Res Opin 6: 255–258

    Google Scholar 

  11. Nash GB, Thomas PRS, Dormandy JA (1988) Abnormal flow properties of white blood cells in patients with severe ischaemia of the leg. Br Med J 296: 1699–1701

    Google Scholar 

  12. Ciuffetti G, Mercuri M, Lombardini R, Maragoni G, Santambrogio L, Mannarino E (1989) Leucocyte behaviour in controlled ischaemia of the calves. J Clin Pathol 42: 1083–1087

    Google Scholar 

  13. Bessler H, Gigal R, Djaldetti M, Zahavi I (1986) Effect of pentoxifylline on the phagocytic activity, cAMP levels, and superoxide anion production by monocytes and polymorphonuclear cells. J Leucocyte Biol 40: 747–754

    Google Scholar 

  14. Till GO, Warren JS, Gannon DE, Chensue SW, Kunkel SL, Varani J, Johnson KJ, Ward PA (1987) Effects of pentoxifylline on phagocyte responses in vitro and acute and chronic inflammatory reactions in vitro. In: Mandell GL, Novick WJ (eds) Pentoxifylline and leucocyte function. Hoechst-Roussel Pharmaceuticals Inc. Sommerville, New Jersey (Proceedings of a symposium held in Key Biscayne, Florida, USA, 30 November-1 December 1987)

    Google Scholar 

  15. Sourbier P, Perianin A, Hakim J (1987) In vitro effect of pentoxifylline on human neutrophil function. In: Mandell GL, Novick WJ (eds) Pentoxifylline and leucocyte function. Hoechst-Roussel Pharmaceuticals Inc. Sommerville, New Jersey (Proceedings of a symposium held in Key Biscayne, Florida, USA, 30 November–1 December 1987)

    Google Scholar 

  16. Ciuffetti G, Mannarino E, Mercuri M, Pasqualini L, Lombardini R, Ott C, Lupattelli G, Paltriccia R (1990) Reactive oxygen metabolites in peripheral vascular disease. VASA 3: 234–236

    Google Scholar 

  17. Mancini G, Carbonara AD, Haremans JF (1965) Immunochemical quantification of antigens by single radial immunodiffusion. Immunochemistry 2: 235–240

    Google Scholar 

  18. Mikita J, Nash G, Dormandy JA (1986) A simple method of preparing white blood cells for filterability testing. Clin Hemorheol 6: 635–639

    Google Scholar 

  19. Lennie SE, Lowe GDO, Barbenel JC, Forbes CD, Foulds WS (1987) Filterability of white blood cell subpopulations, separated by an improved method. Clin Hemorheol 7: 811–816

    Google Scholar 

  20. Nash GB, Jones JG, Mikita J, Christopher B, Dormandy JA (1988) Effects of preparative procedures and of cell activation on flow of white cells through micropore filters. Br J Haematol 70: 171–176

    Google Scholar 

  21. Matthews SB, Hallett MB, Henderson AH, Campbell AK (1985) The adrenochrome pathway. A potential catabolic route for adrenaline metabolism in inflammatory disease. Adv Myocardiol 6: 367–381

    Google Scholar 

  22. Matthews SB, Henderson AH, Campbell AK (1985) The adrenochrome pathway: The major route for adrenalin catabolism by polymorphonuclear leucocytes. J Mol Cell Cardiol 17: 339–348

    Google Scholar 

  23. English D, Roloff JS, Lukens JN (1981) Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils. Blood 58: 129–134

    Google Scholar 

  24. Ciuffetti G, Mercuri M, Mannarino E, Robinson MK, Lennie SE, Lowe GDO (1989) Peripheral vascular disease: Rheologic variables during controlled ischaemia. Circulation 20: 348–352

    Google Scholar 

  25. Ciuffetti G, Mercuri M, Lombardini R, Bellomo G, Corea L, Lowe GDO, Ventura A (1990) Stable angina pectoris and controlled ischaemia. What causes the abnormalities in whole blood filterability? Am Heart J 119: 54–58

    Google Scholar 

  26. Ott E, Fazekas F, Lechner H (1983) Haemorheological effects of pentoxifylline in disturbed blood flow behaviour in patients with cerebrovascular disease. Eur Neurol 22 [Suppl 1]: 105–107

    Google Scholar 

  27. Kobaladze SG, Tschikvadze IV (1979) The use of pentoxifylline in the treatment of ischaemic heart disease. Curr Med Res Opin 6 [Suppl 4]: 12–15

    Google Scholar 

  28. Ernst E, Hammerschmid DE, Bagge U, Matrai A, Dormandy JA (1987) Leucocytes and risk of ischemic diseases. JAMA: 257: 2318–2324

    Google Scholar 

  29. Ernst E (1989) Peripheral vascular disease. Br Med J 299: 873

    Google Scholar 

  30. Mannarino E, Maragoni G, Pasqualini L, Sanchini R, Rossi P, Orlandi U (1987) Transcutaneous oxygen tension behaviour in the different stages of peripheral vascular disease and its correlation with ankle/arm pressure ratio and calf blood flow. Angiology 38: 463–468

    Google Scholar 

  31. Dormandy J (1989) European Consensus Document on Critical Limb Ischaemia. Springer, Berlin Heidelberg New York

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ciuffetti, G., Mercuri, M., Ott, C. et al. Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease. Eur J Clin Pharmacol 41, 511–515 (1991). https://doi.org/10.1007/BF00314976

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00314976

Key words

Navigation