Skip to main content
SpringerLink
Log in

Antiinflammatorische Effekte von Pentoxifyllin

Bedeutung bei herzchirurgischen Eingriffen

Anti-inflammatory effects of pentoxifylline

Importance in cardiac surgery

  • Allgemeinanästhesie
  • Published:
Der Anaesthesist Aims and scope Submit manuscript

Zusammenfassung

Ursprünglich wurde Pentoxifyllin (PTX), ein Methylxanthinderivat zur rheologischen Therapie bei der „Schaufensterkrankheit“ aufgrund einer peripheren arteriellen Verschlusskrankheit oder bei ischämischen zerebrovaskulären Erkrankungen eingesetzt. Neuere Arbeiten weisen jedoch auf verschiedene antiinflammatorische Eigenschaften der Substanz hin, die PTX zu einer interessanten immunmodulatorischen Zusatzmedikation für die Versorgung von herzchirurgischen Patienten macht. Als unspezifischer Phosphodiesterasehemmer (PDE-I) greift PTX auf den unterschiedlichsten Ebenen in die inflammatorischen Signalkaskaden ein und ist dadurch in der Lage, die proinflammatorische Antwort auf verschiedenste Stimuli zu minimieren. Darüber hinaus zeigen mehrere kleine klinische Studien, dass PTX die entzündliche Antwort nach herzchirurgischen Eingriffen unter Einsatz der Herz-Lungen-Maschine (HLM) minimieren könnte und die prophylaktische Anwendung dieser Substanz möglicherweise die postoperative Funktion von gefährdeten Organen, wie Nieren und Leber, sowie die postoperative neurokognitive Funktion verbessern kann.

Abstract

Initially introduced as a rheologic agent for use in intermittent claudication due to peripheral artery disease and in ischemic cerebrovascular disease, the methylxanthine derivative pentoxifylline (PTX) has been shown to possess several anti-inflammatory properties which make this drug an interesting immunomodulating adjunct for the management of patients undergoing cardiac surgery. As an unspecific phosphodiesterase inhibitor PTX ameliorates the inflammatory response following a septic stimulus and blunts organ dysfunction after ischemia-reperfusion injury. Apart from this several small clinical studies have shown that the use of PTX may blunt the inflammatory response induced by cardiac surgery using a cardiopulmonary bypass. Additionally it has been shown that the perioperative application of this drug may improve postoperative function of organs at risk, such as the kidneys and liver.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Akriviadis E, Botla R, Briggs W et al (2000) Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 119:1637–1648

    Article  PubMed  CAS  Google Scholar 

  2. Argel MI, Vittone L, Grassi AO et al (1980) Effect of phosphodiesterase inhibitors on heart contractile behaviour, protein kinase activity and cyclic nucleotide levels. J Mol Cell Cardiol 12:939–954

    Article  PubMed  CAS  Google Scholar 

  3. Asimakopoulos G, Gourlay T (2003) A review of anti-inflammatory strategies in cardiac surgery. Perfusion 18 [Suppl 1]:7–12

    Google Scholar 

  4. Bahlmann L, Weber C, Heinrichs G et al (2006) The effect of pentoxifylline on cognitive dysfunction and mood state after open coronary revascularisation while using the heart-lung machine. Anaesthesiol Intensivmed 47:255–263

    Google Scholar 

  5. Barroso-Aranda J, Schmid-Schonbein GW (1990) Pentoxifylline pretreatment decreases the pool of circulating activated neutrophils, in-vivo adhesion to endothelium, and improves survival from hemorrhagic shock. Biorheology 27:401–418

    PubMed  CAS  Google Scholar 

  6. Beermann B, Ings R, Mansby J et al (1985) Kinetics of intravenous and oral pentoxifylline in healthy subjects. Clin Pharmacol Ther 37:25–28

    PubMed  CAS  Google Scholar 

  7. Bessler H, Gilgal R, Djaldetti M et al (1986) Effect of pentoxifylline on the phagocytic activity, cAMP levels, and superoxide anion production by monocytes and polymorphonuclear cells. J Leukoc Biol 40:747–754

    PubMed  CAS  Google Scholar 

  8. Boldt J, Brosch C, Lehmann A et al (2001) Prophylactic use of pentoxifylline on inflammation in elderly cardiac surgery patients. Ann Thorac Surg 71:1524–1529

    Article  PubMed  CAS  Google Scholar 

  9. Boldt J, Brosch C, Piper SN et al (2001) Influence of prophylactic use of pentoxifylline on postoperative organ function in elderly cardiac surgery patients. Crit Care Med 29:952–958

    Article  PubMed  CAS  Google Scholar 

  10. Cagli K, Ulas MM, Ozisik K et al (2005) The intraoperative effect of pentoxifylline on the inflammatory process and leukocytes in cardiac surgery patients undergoing cardiopulmonary bypass. Perfusion 20:45–51

    Article  PubMed  Google Scholar 

  11. Coe DA, Freischlag JA, Johnson D et al (1997) Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury. J Surg Res 67:21–25

    Article  PubMed  CAS  Google Scholar 

  12. Coimbra R, Melbostad H, Loomis W et al (2006) LPS-induced acute lung injury is attenuated by phosphodiesterase inhibition: effects on proinflammatory mediators, metalloproteinases, NF-kappaB, and ICAM-1 expression. J Trauma 60:115–125

    Article  PubMed  CAS  Google Scholar 

  13. Coimbra R, Melbostad H, Loomis W et al (2005) Phosphodiesterase inhibition decreases nuclear factor-kappaB activation and shifts the cytokine response toward anti-inflammatory activity in acute endotoxemia. J Trauma 59:575–582

    PubMed  CAS  Google Scholar 

  14. Coimbra R, Porcides RD, Melbostad H et al (2005) Nonspecific phosphodiesterase inhibition attenuates liver injury in acute endotoxemia. Surg Infect 6:73–85

    Article  Google Scholar 

  15. De Campos T, Deree J, Martins JO et al (2008) Pentoxifylline attenuates pulmonary inflammation and neutrophil activation in experimental acute pancreatitis. Pancreas 37:42–49

    Article  CAS  Google Scholar 

  16. Ege T, Arar C, Canbaz S et al (2004) The importance of aprotinin and pentoxifylline in preventing leukocyte sequestration and lung injury caused by protamine at the end of cardiopulmonary bypass surgery. Thorac Cardiovasc Surg 52:10–15

    Article  PubMed  CAS  Google Scholar 

  17. Faist E, Kim C (1998) Therapeutic immunomodulatory approaches for the control of systemic inflammatory response syndrome and the prevention of sepsis. New Horiz 6:S97–S102

    PubMed  CAS  Google Scholar 

  18. Friedrich M, Sterry W, Klein A et al (2001) Addition of pentoxifylline could reduce the side effects of fumaric acid esters in the treatment of psoriasis. Acta Derm Venereol 81:429–430

    Article  PubMed  CAS  Google Scholar 

  19. Golbasi I, Akbas H, Ozdem S et al (2006) The effect of pentoxifylline on haemolysis during cardiopulmonary bypass in open-heart surgery. Acta Cardiol 61:7–11

    Article  PubMed  Google Scholar 

  20. Groesdonk HV, Bauer A, Kreft B et al (2009) Urodilatin and pentoxifylline prevent the early onset of Escherichia coli-induced acute renal failure in a model of isolated perfused rat kidney. Kidney Blood Press Res 32:81–90

    Article  PubMed  CAS  Google Scholar 

  21. Heinze H, Rosemann C, Weber C et al (2007) A single prophylactic dose of pentoxifylline reduces high dependency unit time in cardiac surgery – a prospective randomized and controlled study. Eur J Cardiothorac Surg 32:83–89

    Article  PubMed  Google Scholar 

  22. Hemmer CJ, Hort G, Chiwakata CB et al (1997) Supportive pentoxifylline in falciparum malaria: no effect on tumor necrosis factor alpha levels or clinical outcome: a prospective, randomized, placebo-controlled study. Am J Trop Med Hyg 56:397–403

    PubMed  CAS  Google Scholar 

  23. Hoffmann H, Markewitz A, Kreuzer E et al (1998) Pentoxifylline decreases the incidence of multiple organ failure in patients after major cardio-thoracic surgery. Shock 9:235–240

    Article  PubMed  CAS  Google Scholar 

  24. Iskesen I, Kurdal AT, Kahraman N et al (2009) Preoperative oral pentoxifylline for management of cytokine reactions in cardiac surgery. Heart Surg Forum 12:E100–E104

    Article  PubMed  Google Scholar 

  25. Iskesen I, Saribulbul O, Cerrahoglu M et al (2006) Pentoxifylline affects cytokine reaction in cardiopulmonary bypass. Heart Surg Forum 9:E883–E887

    Article  PubMed  Google Scholar 

  26. Kleinschmidt S, Bauer M, Grundmann U et al (1997) Effect of gamma-hydroxybutyric acid and pentoxifylline on kidney function parameters in coronary surgery interventions. Anaesthesiol Reanim 22:102–107

    PubMed  CAS  Google Scholar 

  27. Koul BL, Nordhas O, Sonnenfeld T et al (1984) The effect of pentoxifylline on impaired red cell deformability following open-heart surgery. Scand J Thorac Cardiovasc Surg 18:129–131

    PubMed  CAS  Google Scholar 

  28. Kowalski J, Kosmider M, Pasnik J et al (1999) Pentoxifylline decreases neutrophil respiratory bursts in patients with stable angina. Fundam Clin Pharmacol 13:237–242

    Article  PubMed  CAS  Google Scholar 

  29. Lauterbach R, Pawlik D, Kowalczyk D et al (1999) Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: a placebo-controlled, double-blind trial. Crit Care Med 27:807–814

    Article  PubMed  CAS  Google Scholar 

  30. Lauterbach R, Zembala M (1996) Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis. Eur J Pediatr 155:404–409

    Article  PubMed  CAS  Google Scholar 

  31. McKinley BA, Butler BD (1999) Comparison of skeletal muscle PO2, PCO2, and pH with gastric tonometric P(CO2) and pH in hemorrhagic shock. Crit Care Med 27:1869–1877

    Article  PubMed  CAS  Google Scholar 

  32. Noel C, Hazzan M, Coppin MC et al (1997) A randomized controlled trial of pentoxifylline for the prevention of delayed graft function in cadaveric kidney graft. Clin Transplant 11:169–173

    PubMed  CAS  Google Scholar 

  33. Otani S, Kuinose M, Murakami T et al (2008) Preoperative oral administration of pentoxifylline ameliorates respiratory index after cardiopulmonary bypass through decreased production of IL-6. Acta Med Okayama 62:69–74

    PubMed  CAS  Google Scholar 

  34. Pereda J, Gomez-Cambronero L, Alberola A et al (2006) Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats. Br J Pharmacol 149:450–455

    Article  PubMed  CAS  Google Scholar 

  35. Rieckmann P, Weber F, Gunther A et al (1996) Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis. J Neuroimmunol 64:193–200

    Article  PubMed  CAS  Google Scholar 

  36. Sakaguchi T, Hayashi S (1978) Pentoxifylline: pharmacology and clinical trials of pentoxifylline. Pharmacometrics 15:153–183

    CAS  Google Scholar 

  37. Sampaio EP, Moraes MO, Nery JA et al (1998) Pentoxifylline decreases in vivo and in vitro tumour necrosis factor-alpha (TNF-alpha) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL). Clin Exp Immunol 111:300–308

    Article  PubMed  CAS  Google Scholar 

  38. Schade UF, Von Der Bosch J, Schonharting M (1989) Pentoxifylline increases survival of mice in endotoxic shock. Prog Clin Biol Res 301:223–227

    PubMed  CAS  Google Scholar 

  39. Schreiber P, Schröppel M, Heidrich H (1983) Effects of naftidrofuryl, pentoxifylline and bencyclane on the renal blood flow and renal excretion of conscious dogs. Herz 15:195–201

    CAS  Google Scholar 

  40. Shaw SM, Shah MK, Williams SG et al (2009) Immunological mechanisms of pentoxifylline in chronic heart failure. Eur J Heart Fail 11:113–118

    Article  PubMed  CAS  Google Scholar 

  41. Silomon M, Pizanis A, Larsen R et al (1998) Pentoxifylline prevention of altered hepatocyte calcium regulation during hemorrhagic shock/resuscitation. Crit Care Med 26:494–500

    Article  PubMed  CAS  Google Scholar 

  42. Sliwa K, Skudicky D, Candy G et al (2002) The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum cardiomyopathy. Eur J Heart Fail 4:305–309

    Article  PubMed  CAS  Google Scholar 

  43. Sliwa K, Woodiwiss A, Candy G et al (2002) Effects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 90:1118–1122

    Article  PubMed  CAS  Google Scholar 

  44. Sliwa K, Woodiwiss A, Kone VN et al (2004) Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study. Circulation 109:750–755

    Article  PubMed  CAS  Google Scholar 

  45. Sliwa K, Woodiwiss A, Libhaber E et al (2004) C-reactive protein predicts response to pentoxifylline in patients with idiopathic dilated cardiomyopathy. Eur J Heart Fail 6:731–734

    Article  PubMed  CAS  Google Scholar 

  46. Staubach KH, Schroder J, Stuber F et al (1998) Effect of pentoxifylline in severe sepsis: results of a randomized, double-blind, placebo-controlled study. Arch Surg 133:94–100

    Article  PubMed  CAS  Google Scholar 

  47. Trajkovic V, Badovinac V, Popadic D et al (1997) Cell-specific effects of pentoxifylline on nitric oxide production and inducible nitric oxide synthase mRNA expression. Immunology 92:402–406

    Article  PubMed  CAS  Google Scholar 

  48. Tsang GM, Allen S, Pagano D et al (1996) Pentoxifylline preloading reduces endothelial injury and permeability in cardiopulmonary bypass. ASAIO J 42:M429–M434

    Article  PubMed  CAS  Google Scholar 

  49. Turkoz R, Yorukoglu K, Akcay A et al (1996) The effect of pentoxifylline on the lung during cardiopulmonary bypass. Eur J Cardiothorac Surg 10:339–346

    Article  PubMed  CAS  Google Scholar 

  50. Ustunsoy H, Sivrikoz MC, Bakir K et al (2002) The inhibition of pro-inflammatory cytokines with pentoxifylline in the cardiopulmunary bypass lung. Respir Med 96:275–279

    Article  PubMed  CAS  Google Scholar 

  51. Ustunsoy H, Sivrikoz MC, Tarakcioglu M et al (2006) The effects of pentoxifylline on the myocardial inflammation and ischemia-reperfusion injury during cardiopulmonary bypass. J Card Surg 21:57–61

    Article  PubMed  Google Scholar 

  52. Van Leenen D, Van Der Poll T, Levi M et al (1993) Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees. J Immunol 151:2318–2325

    Google Scholar 

  53. Vittone L, Chiappe LE, Argel MI et al (1980) The mechanical and biochemical effects of pentoxifylline on the perfused rat heart. Experientia 36:1088–1090

    Article  PubMed  CAS  Google Scholar 

  54. Wang P, Ba ZF, Morrison MH et al (1992) Mechanism of the beneficial effects of pentoxifylline on hepatocellular function after trauma hemorrhage and resuscitation. Surgery 112:451–457; discussion 457–458

    PubMed  CAS  Google Scholar 

  55. Wang W, Tam WF, Hughes CC et al (1997) c-Rel is a target of pentoxifylline-mediated inhibition of T lymphocyte activation. Immunity 6:165–174

    Article  PubMed  CAS  Google Scholar 

  56. Wang W, Zolty E, Falk S et al (2006) Pentoxifylline protects against endotoxin-induced acute renal failure in mice. Am J Physiol Renal Physiol 291:F1090–F1095

    Article  PubMed  CAS  Google Scholar 

  57. Ward A, Clissold SP (1987) Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 34:50–97

    Article  PubMed  CAS  Google Scholar 

  58. Watanabe H, Furukawa Y, Chiba S (1982) Cardiovascular effects of aminophylline and pentoxifylline on intact dogs and isolated dog atria. Jpn Heart J 23:235–243

    PubMed  CAS  Google Scholar 

  59. Weber F, Polak T, Gunther A et al (1998) Synergistic immunomodulatory effects of interferon-beta1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing-remitting multiple sclerosis. Ann Neurol 44:27–34

    Article  PubMed  CAS  Google Scholar 

  60. Wenisch C, Looareesuwan S, Wilairatana P et al (1998) Effect of pentoxifylline on cytokine patterns in the therapy of complicated Plasmodium falciparum malaria. Am J Trop Med Hyg 58:343–347

    PubMed  CAS  Google Scholar 

  61. Yada-Langui MM, Coimbra R, Lancellotti C et al (2000) Hypertonic saline and pentoxifylline prevent lung injury and bacterial translocation after hemorrhagic shock. Shock 14:594–598

    Article  PubMed  CAS  Google Scholar 

  62. Zhang M, Xu YJ, Saini HK et al (2005) Pentoxifylline attenuates cardiac dysfunction and reduces TNF-alpha level in ischemic-reperfused heart. Am J Physiol Heart Circ Physiol 289:H832–H839

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Klinik für Thorax- und Herz-Gefäßchirurgie, Universitätskliniken des Saarlandes, Kirrbergerstr., 66421, Homburg/Saar, Deutschland

    H.V. Groesdonk

  2. Klinik für Anästhesiologie, Universität zu Lübeck, Lübeck, Deutschland

    H.V. Groesdonk, M. Heringlake & H. Heinze

Authors
  1. H.V. Groesdonk
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Heringlake
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Heinze
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H.V. Groesdonk.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Groesdonk, H., Heringlake, M. & Heinze, H. Antiinflammatorische Effekte von Pentoxifyllin. Anaesthesist 58, 1136–1143 (2009). https://doi.org/10.1007/s00101-009-1626-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00101-009-1626-9

Schlüsselwörter

Keywords

Search

Navigation