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Cardiovascular reactions and respiratory events during platelet activating factor-induced shock

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Summary

The platelet activating factor (PAF), a low molecular phospholipid, plays an important role in inflammation, anaphylaxis, and shock state development. In the isolated perfused guinea pig heart, PAF induces a decrease in coronary flow and cardiac contractility and atrioventricular conduction disturbances. Furthermore, PAF mediates a powerful bronchoconstrictory action causing a severe impairment in respiratory function. In the present study an attempt was made to separate cardiac from respiratory events during PAF-induced shock in vivo. PAF was injected intravenously (0.1–10 μg/kg) into anesthetized guinea pigs ventilated with room air or 100% oxygen. Administration of 10 μg/kg PAF was uniformly lethal: already within 2 min, cardiac output decreased by 60% and end-diastolic left ventricular pressure increased markedly indicating cardiac failure. ECG recordings showed signs of acute myocardial ischemia. Arrhythmias occurred in terms of atrioventricular conduction delay. Blood pressure initially increased, then declined continuously to below baseline within 10 min. All animals died within 25 min. Ventilation with room air was paralleled by development of severe hypoxia. However, under ventilation with 100% oxygen a dissociation between PAF-mediated cardiac and respiratory effects occurred. It is concluded that the PAF-induced shock is primarily based on direct cardiac damage. Furthermore, the ECG signs of ischemia are most likely due to coronary spasms.

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References

  1. Benveniste J, Henson PM, Cochrane CG (1972) Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor. J Exp Med 136:1536–1377

    Google Scholar 

  2. Benveniste J, Tencé M, Varenne P, Bidault J, Boullet C, Polonsky J (1979) Semi-synthèse et structure purposée du facteur activant les plaquettes (PAF); PAF-acéter, un alkyl éther analogue de la lysophosphatidylcholine. CR Acad Sci Ser D 289:1037–1040

    Google Scholar 

  3. Bessin P, Bonnet J, Apffel D, Soulard C, Desgroux L, Pelas I, Benveniste J (1983) Acute circulatory collapse caused by platelet-activating factor (PAF-acether) in dogs. Eur J Pharmacol 86:403–413

    PubMed  Google Scholar 

  4. Björk J, Smedegard G (1983) Acute microvascular effects of PAF-acether as studied by intravital microscopy. Eur J Pharmacol 96:87–94

    PubMed  Google Scholar 

  5. Blank ML, Snyder F, Byers LW, Brooks B, Muirhead EE (1979) Antihypertensive activity of an alkyl ether analog of phosphatidylcholine. Biochem Biophys Res Comm 90:1194–1200

    PubMed  Google Scholar 

  6. Braquet P, Rola-Pleszezynski M (1987) The role of PAF in immunological responses: A review. Prostaglandins 34:143–147

    PubMed  Google Scholar 

  7. Camussi G, Aglietta M, Coda R, Bussolino F, Piacibello W, Tetta C (1981) Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: Monocytes, polymorphonuclear neutrophils and basophils. Immunology 42:191–199

    PubMed  Google Scholar 

  8. Camussi G, Brentjens JR (1987) The role of platelet-activating factor in inflammation. In: Snyder F (ed) Platelet-activating factor and related lipid mediators. Plenum Press, New York, pp 299–322

    Google Scholar 

  9. Chignard M, LeCouedic JP, Tencé M, Vargaftig BB, Benveniste J (1979) The role of platelet-activating factor in platelet aggregation. Nature 279:799–800

    PubMed  Google Scholar 

  10. Demopoulos CA, Pinckard RN, Hanahan DJ (1979) Platelet-activating factor: Evidence for 1-O-alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). J Biol Chem 254:9355–9358

    PubMed  Google Scholar 

  11. 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 127:799–808

    PubMed  Google Scholar 

  12. Ezra D, Laurindo FRM, Czaja JF, Snyder F, Goldstein RE, Feuerstein G (1987) Cardiac and coronary consequences of intracoronary platelet activating factor infusion in the domestic pig. Prostaglandins 34:41–57

    PubMed  Google Scholar 

  13. Feuerstein G, Goldstein RE (1987) Effect of PAF on the cardiovascular system. In: Snyder F (ed) Platelet-activating factor and related lipid mediators. Plenum Press, New York, pp 403–424

    Google Scholar 

  14. Koltai M, Lepran I, Szekeres L, Viossat I, Chabrier E, Braquet P (1986) Effect of BN 52021, a specific PAF-acether antagonist on cardiac anaphylaxis in Langendorff hearts isolated from passively sensitized guinea-pigs. Eur J Pharmacol 130:133–136

    PubMed  Google Scholar 

  15. Lefer AM, Müller HF, Smith JB (1984) Pathophysiological mechanisms of sudden death induced by platelet activating factor. Br J Pharmacol 83:125–130

    PubMed  Google Scholar 

  16. Levi R, Burke JA, Guo Z-G, Hattori Y, Hoppens CM, McManus LM, Hanahan DJ, Pinckard RN (1984) Acetyl glyceryl ether phosphorylcholine (AGEPC) a putative mediator of cardiac anaphylaxis in the guinca pig. Circ Res 54:117–124

    PubMed  Google Scholar 

  17. Neumann G, Erhardt W, Oberhuber B, Fritsch R, Blümel G (1980) A new highly potent and short-acting analgesic, Carfentanyl (R33799) in combination with the hypnotic agent Etomidat (R26490), as a method of anaesthesia in guinea pigs. Res Exp Med 177:135–143

    Google Scholar 

  18. Pinckard RN, Farr RS, Hanahan DJ (1979) Physicochemical and functional identity of rabbit platelet activating factor (PAF) released in vivo during IgE anaphylaxis with PAF released in vitro from IgE-sensitized basophiles. J Immunol 123:1847–1857

    PubMed  Google Scholar 

  19. Piper PJ, Stewart AG (1986) Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet-activating factor is mediated by leukotriene C4. Br J Pharmacol 88:595–605

    PubMed  Google Scholar 

  20. Piper PJ, Stewart AG (1987) Antagonism of vasoconstriction induced by platelet-activating factor in guinea-pig perfused hearts by selective platelet-activating factor receptor antagonists. Br J Pharmacol 90:771–783

    PubMed  Google Scholar 

  21. Sanchez Crespo M, Inarrea P, Nieto ML, Fernandez-Gallardo S (1986) Evidence of a role for PAF-acether in the pathophysiology of the shock state. Pharmacol Res Comm 18:181–196

    Google Scholar 

  22. Stahl GL, Lefer DJ, Lefer AM (1987) PAF-acether induced cardiac dysfunction in the isolated perfused guinea pig heart. Naunyn-Schmiedeberg's Arch Pharmacol 336:459–463

    Google Scholar 

  23. Stewart AG, Piper PJ (1986) Platelet-activating factor-induced vasoconstriction in rat isolated, perfused hearts: Contribution of cyclooxygenase and lipoxygenase arachidonic acid metabolites. Pharmacol Res Comm 18:Suppl 163–172

    Google Scholar 

  24. Stewart AG, Piper PJ (1988) Platelet-activating factor and the cardiovascular system: involvement in cardiac anaphylaxis. Prog Biochem Pharmacol 22:132–140

    PubMed  Google Scholar 

  25. Sybertz EJ, Watkins RW, Baum T, Pula K, Rivelli M (1985) Cardiac, coronary and peripheral vascular effects of acetyl glyceryl ether phosphoryl choline in the anesthetized dog. J Pharmacol Exp Ther 232:156–162

    PubMed  Google Scholar 

  26. Terashita ZI, Imura Y, Nishikawa K, Sumida S (1985) Is platelet activating factor (PAF) a mediator of endotoxin shock? Eur J Pharmacol 109:257–261

    PubMed  Google Scholar 

  27. Vargaftig BB, Braquet PG (1987) PAF-acether today — relevance for acute experimental anaphylaxis. Br Med Bull 43:312–335

    PubMed  Google Scholar 

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  1. S. B. Felix

    Present address: I. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 8000, München 80, FRG

Authors and Affiliations

  1. I. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 8000, München 80, FRG

    G. Baumann, P. Raschke, C. Maus & W. E. Berdel

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  1. S. B. Felix
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  2. G. Baumann
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  3. P. Raschke
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Felix, S.B., Baumann, G., Raschke, P. et al. Cardiovascular reactions and respiratory events during platelet activating factor-induced shock. Basic Res Cardiol 85, 217–226 (1990). https://doi.org/10.1007/BF01907110

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