The Possible Roles of Lipoxygenase Products of Arachidonic Acid Metabolism and of Platelet Activating Factor in Shock

  • J. R. Parratt
  • N. Pacitti
Conference paper
Part of the Update in Intensive Care and Emergency Medicine book series (UICM, volume 4)


Lipoxygenase products, such as leukotrienes and platelet activating factor (PAF) are the most recently described and studied vasoactive agents which have been suggested as chemical mediators in shock. They might also be more generally involved in some of the pathophysiological consequences of tissue underperfusion. Neither were discussed to any extent in two of the most recent reviews on neurohumoral agents and their release in shock [1, 2] and it is as yet too early to decide on their importance relative to other more established mediators. This brief review attempts to summarize the limited experimental data available on their actions and possible role in shock. Hopefully, it will provide pointers for more clearly defining their importance in tissue low perfusion states.


Platelet Activate Factor Systemic Hypotension Circ Shock Lipoxygenase Inhibitor Ginkgo Biloba Extract 
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.
    I. Lefer AM (1983) Role of prostaglandins and thromboxanes in shock states. In: Altura BM, Lefer AM, Schumer W (eds) Handbook of Shock and Trauma. Raven Press, New York, pp 355–376Google Scholar
  2. 2.
    Parratt JR (1983) Neurohumoral agents and their release in shock. In: Altura BM, Lefer AM, Schumer W (eds) Handbook of Shock and Trauma. Raven Press, New York, pp 311336Google Scholar
  3. 3.
    Filep J, Foldes-Filep E, Frohlich JC (1987) Vascular responses to leukotriene B, C and D following FPL 55712, indomethacin, saralasin, phentolamine and verapamil in the conscious rat. Br J Pharmac 90: 431–439Google Scholar
  4. 4.
    Letts LG, Piper PJ, Newman DA (1983) Leukotrienes and their action in the coronary circulation. In: Piper PJ (ed) Leukotrienes and Other Lipoxygenase Products. John Wiley & Sons, Chichester, pp 94–107Google Scholar
  5. 5.
    Parratt JR, Wainwright CL (1986) Ventricular arrhythmias induced by local injections of vasoconstrictors following coronary occlusion. Br J Pharmac 88: 397 PGoogle Scholar
  6. 6.
    Lux EW, Feuerstein G, Faden AI (1983) Alteration to leukotriene D4 hypotension by thyrotropin releasing hormone. Nature (London) 301: 822–824CrossRefGoogle Scholar
  7. 7.
    Parratt JR (1985) The role of arachidonic acid metabolites in endotoxin shock I: lipoxygenase products. In: Hinshaw LB (ed) Handbook of Endotoxin volume 2, Pathophysiology of Endotoxin. Elsevier, Amsterdam, pp 203–236Google Scholar
  8. 8.
    Ogletree ML, Oates JA, Brigham KL, Hubbard WC (1982) Evidence for pulmonary release of 5-hydroxyeicosatetraenoic acid (5-HETE) during endotoxemia in unanesthetized sheep. Prostaglandins 23: 459–468PubMedCrossRefGoogle Scholar
  9. 9.
    Snapper JR, Brigham KL (1985) Arachidonic products as mediators of diffuse lung injury. In: Said SI (ed) The Pulmonary Circulation and Acute Lung Injury. Futura, New York, pp 321–336Google Scholar
  10. 10.
    Hagmann W, Denzlinger C, Keppler D (1984) Role of peptide leukotrienes and their hepatobiliary elimination in endotoxin action. Circ Shock 14: 223–235PubMedGoogle Scholar
  11. 11.
    Coker SJ, Hughes B, Parratt JR, Rodger IW, Zeitlin IJ (1983) The release of prostanoids during acute pulmonary response to Escherichia coli endotoxin in anesthetized cats. Br J Pharmacol 78: 561–570PubMedGoogle Scholar
  12. 12.
    Smith M, Gunther R, Zaiss C, Flynn J, Demling R (1981) Pulmonary microvascular injury from lipoxygenase infusion: comparison with endotoxemia. Circ Shock 8: 647–656PubMedGoogle Scholar
  13. 13.
    Abaitey AK, Parratt JR (1976) Cardiovascular effects of diethylcarbamazine citrate. Br J Pharmacol 56: 219–228PubMedGoogle Scholar
  14. 14.
    Abaitey AK, Parratt JR (1977) The effects of diethylcarbamazine citrate on smooth muscle. J Pharm Pharmacol 29: 428–432PubMedCrossRefGoogle Scholar
  15. 15.
    Pacitti N, Bryson S, McKechnie K, Rodger IW, Parratt JR (1987) Leukotriene antagonist FPL 57231 prevents the acute pulmonary effects of Escherichia coli endotoxin in cats. Circ Shock 21: 155–167PubMedGoogle Scholar
  16. 16.
    Ahmed T, Wassermann M, Muccitelli R, Tucker S, Gazeloglu H, Marchette B (1986) Endotoxin-induced changes in pulmonary haemodynamics and respiratory mechanics–role of lipoxygenase and cyclooxygenase products. Am Rev Respir Dis 134: 1149–1157PubMedGoogle Scholar
  17. 17.
    Goldberg RN, Suguihara C, Streitfeld MM, Bancalari A, Clark MR, Bancalari E (1986) Effects of a leukotriene antagonist on the early hemodynamic manifestations of Group B streptococcal sepsis in piglets. Pediatric Res 20: 1004–1008CrossRefGoogle Scholar
  18. 18.
    Cook JA, Wise WC, Halushka PV (1985) Protective effect of a selective leukotriene antagonist in endotoxemia in the rat. J Pharmacol Exp Ther 235: 470–474PubMedGoogle Scholar
  19. 19.
    Lefer AM (1986) Leukotrienes as mediators of ischemia and shock. Biochem Pharmacol 35: 123–127PubMedCrossRefGoogle Scholar
  20. 20.
    Hagmann W, Keppler D (1982) Leukotriene antagonists prevent endotoxin lethality. Naturwissenschaften 69: 594–595PubMedCrossRefGoogle Scholar
  21. 21.
    Hagmann W, Fritz MM, Keppler D (1983) Leukotrienes and endotoxin lethality. In: Piper PJ (ed) Leukotrienes and Other Lipoxygenase Products. John Wiley & Sons, Chichester, pp 128–133Google Scholar
  22. 22.
    Coker SJ, Parratt JR (1984) The effects of nafazatrom on arrhythmias and prostanoid release during coronary artery occlusion and reperfusion in anaesthetized greyhounds. J Mol Cell Cardiol 16: 43–52PubMedCrossRefGoogle Scholar
  23. 23.
    Feuerstein G, Bayorh MA, Stull R (1985) Effects of nafazatrom on cardiovascular sympathetic, and endocrine responses to hemorrhagic shock in conscious rats. Circ Shock 17: 223232Google Scholar
  24. 24.
    Hall-Angeras M, Saljo A, Hasselgren P-O (1986) Effect of methylprednisolone, indomethacin and diethylcarbamazine on survival rate following trauma and sepsis in rats. Circ Shock 20: 231–238PubMedGoogle Scholar
  25. 25.
    Dunn R, Rogus F, Nolan P, Phuangsub A, Barrett J (1985) Diethylcarbamazine, a leukotriene inhibitor, improves in-vitro microcirculatory flow during endotoxaemia. Circ Shock 16: Abstract 88 p 69Google Scholar
  26. 26.
    Schade OF (1986) Involvement of lipoxygenases in the activation of mouse macrophages by endotoxin. Biochem Biophys Res Commun 138: 842–849PubMedCrossRefGoogle Scholar
  27. 27.
    Braquet P, Tongui L, Vargaftig BB, Shen TY (1987) Perspectives in platelet activating factor research. Pharmacol Res (in press)Google Scholar
  28. 28.
    Vargaftig BB, Fouque F, Lefort J (1984) Aggregation plaquettaire et PAF-acether. Interférences pharmacologiques. J Pharmacol (Paris) 15: 69–84Google Scholar
  29. 29.
    Burhop KE, Van der Zee H, Bizios R, Kaplan JE, Malik AB (1986) Pulmonary vascular responses to platelet-activating factor in awake sheep and the role of cyclooxygenase metabolites. Am Rev Respir Dis 134: 548–554PubMedGoogle Scholar
  30. 30.
    Hamasaki Y, Mojarad M, Saga T, Hsin-Hsiung T, Said SI (1984) Platelet-activating factor raises airway and vascular pressures and induces edema in lungs perfused with platelet-free solution. Am Rev Respir Dis 129: 742–746PubMedGoogle Scholar
  31. 31.
    Bessin P, Bonnet J, Apffel D (1983) Acute circulatory collapse caused by platelet-activating factor ( PAF-acether) in dogs. Eur J Pharmacol 86: 403–413Google Scholar
  32. 32.
    Doebber TW, Wu MS, Robbins JC, Choy BM, Chang MN, Shen TY (1985) Platelet-activating factor (PAF) involvement in endotoxin-induced hypotension in rats. Studies with PAF-receptor antagonist kadsurenone. Biochem Biophys Res Commun 127: 799–808Google Scholar
  33. 33.
    Inarrea P, Gomez-Cambronero J, Pascual J, del Carmen Ponte M, Hernando L, Sanchez-Crespo M (1985) Synthesis of PAF-acether and blood volume changes in Gram-negative sepsis. Immunopharmacology 9: 45–52PubMedCrossRefGoogle Scholar
  34. 34.
    Toth PD, Mikulaschek AW (1986) Effects of a platelet-activating factor antagonist, CV-3988, on different shock models in the rat. Circ Shock 20: 193–203PubMedGoogle Scholar
  35. 35.
    Terashita Z, Imura Y, Nishikawa K, Sumida S (1985) Is platelet-activating factor (PAF) a mediator of endotoxin shock? Eur J Pharmacol 109: 257–261PubMedCrossRefGoogle Scholar
  36. 36.
    Wallace JL, Whittle BJR (1986) Prevention of endotoxin-induced gastrointestinal damage by CV-3988, an antagonist of platelet-activating factor. Eur J Pharmacol 124: 209–210PubMedCrossRefGoogle Scholar
  37. 37.
    Etienne A, Hecquet F, Soulard C, Spinnewyn B, Clostre F, Braquet P (1985) In vivo inhibition of plasma protein leakage and Salmonella enteritidis–induced mortality in the rat by a specific paf-acether antagonist: BN52021. Agents Actions 17: 368–370CrossRefGoogle Scholar
  38. 38.
    Handley DA, Van Valen RG, Melden MK, Flury S, Lee ML, Saunders RN (1986) Inhibition and reversal of endoxotin-, aggregated IgG- and paf-induced hypotension in the.rat by SRI 63–072, a paf receptor antagonist. Immunopharmacology 12: 11–16PubMedCrossRefGoogle Scholar
  39. 39.
    Okamoto M, Yoshida K, Nishikawa M, Kohsaka M, Aoki H (1986) Platelet activating factor (PAF) involvement in endotoxin-induced thrombocytopenia in rabbits: Studies with FR-900452, a specific inhibitor of PAF. Thrombosis Res 42: 661–671CrossRefGoogle Scholar
  40. 40.
    Issekutz AC, Szpejda M (1986) Evidence that platelat activating factor may mediate some acute inflammatory responses. Studies with the platelet-activating factor antagonist, CV3988. Lab Invest 54: 275–281PubMedGoogle Scholar
  41. 41.
    McKechnie K, Furman BL, Parratt JR (1986) Modification by oxygen free radical scavengers of the metabolic and cardiovascular effects of endotoxin infusion in conscious rats. Circ Shock 19: 429–439PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • J. R. Parratt
  • N. Pacitti

There are no affiliations available

Personalised recommendations