Skip to main content
Log in

Ischemia aggravating effects of platelet-activating factor in acute myocardial ischemia

  • Original Contributions
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Summary

The effect of platelet-activating factor (PAF) was studied during the acute phase of myocardial ischemia in cats. PAF infusion (0.75 μg/kg/h for 4.5 h) in anesthetized, open-chest cat decreased arterial blood pressure, but did not influence heart rate or biochemical indices of cell integrity. The same dose of PAF, however, started 30 min after coronary ligation, resulted in a significantly higher elevation of plasma creatine phosphokinase (CK) activity and a reduced CK content in the region of the ischemic myocardium. Treatment with the thromboxane A2 synthetase inhibitor, CGS-13080, significantly attenuated the PAF-aggravated ischemic cellular damage. These experiments suggest that hypoxiagenerated PAF may contribute to the aggravation of myocardial ischemia, part of which appears to be due to PAF-induced release of thromboxane A2.

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. Benveniste J, Henson PM, Cochrane CG (1972) Leukocyte-dependent histamine release from rabbit platelets: the role of IgE-basophils and platelet-activating factor. J Exp Med 136:1356

    PubMed  Google Scholar 

  2. Benveniste J, Roubin R, Chignard M, Jouvin-Marche E, LeCouedic JP (1982) Release of platelet-activating factor (PAF-acether) and 2-lyso-PAF-acether from three cell types. Agents and Actions 12:711

    PubMed  Google Scholar 

  3. Benveniste J, Boullet C, Brink C, Labat C (1983) The actions of PAF-acether (platelet-activating factor) on guinea-pig isolated heart preparation. Br J Pharmacol 80:81

    PubMed  Google Scholar 

  4. Bjork J, Lindbrom L, Gerdin B, Smedegard G, Arfors KE, Benveniste J (1983) PAF-acether (platelet-activating factor) increases microvascular permeability and affects endothelium-granulocyte interaction in microvascular beds. Acta Physiol Scand 119:305

    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

    PubMed  Google Scholar 

  6. Burke SE, DiCola G, Lefer AM (1983) Protection of ischemic cat myocardium by CGS-13080, a selective potent thromboxane A2 synthesis inhibitor. J Cardiovasc Pharmacol 5:842

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  8. Chignard M, Wal F, Lefort J, Vargaftig BB (1982) Inhibition by sulphinpyrazone of the platelet-dependent bronchoconstriction due to platelet-activating factor (PAF-acether) in the guinea-pig. Eur J Pharmacol 78:71

    PubMed  Google Scholar 

  9. Coker SJ, Ledingham IMcA, Parratt JR, Zeitlin IJ (1981) Aspirin inhibits the early myocardial release of thromboxane B2 and ventricular ectopic activity following acute coronary artery occlusion in dogs. Br J Pharmacol 72:593

    PubMed  Google Scholar 

  10. Gorman RR, Morton DR, Hopkins NK, Lin AH (1983) Acetyl glyceryl ether phosphorylcholine stimulates leukotriene B4 synthesis and cyclic AMP accumulation in human polymorphonuclear leukocytes. In: Samuelsson B, Paoletti R, Ramwell P (eds). Adv Prostaglandin, Thromboxane, Leukotriene Res Vol 12. Raven Press, New York, p 57

    Google Scholar 

  11. Lefer AM, Ogletree ML, Smith JB, Silver MJ, Nicolaou KC, Barnette WE, Gasic GP (1978) Prostacyclin: A potentially valuable agent for preserving myocardial tissue in acute myocardial ischemia. Science 200:52

    PubMed  Google Scholar 

  12. Lefer AM, Polansky EW (1979) Beneficial effects of ibuprofen in acute myocardial ischemia. Cardiology 69:265

    Google Scholar 

  13. Lefer AM, Smith III EF, Araki H, Smith JB, Aharony D, Claremon DA, Magolda RL, Nicolaou KC (1980) Dissociation of vasoconstrictor and platelet aggregatory activities of thromboxane by carbocyclic thromboxane A2, a stable analog of thromboxane A2. Proc Natl Acad Sci USA 7:1706

    Google Scholar 

  14. Lefer AM, Smith JB, Müller HF (1984) Pathophysiologic mechanisms of sudden death induced by platelet-activating factor (PAF). (In Press, Br J Pharmacol)

  15. Leprán I, Koltai M, Szekeres L (1981) Effect of nonsteroid anti-inflammatory drugs in experimental myocardial infarction in rats. Eur J Pharmacol 69:235

    PubMed  Google Scholar 

  16. McManus LH, Hanahan DJ, Demopoulos CA, Pinckard RN (1980) Pathobiology of intravenous infusion of acetyl glyceryl ether phosphorylcholine (AGEPC), a synthetic platelet-activating factor (PAF), in the rabbit. J Immunol 124:2919

    PubMed  Google Scholar 

  17. Myers A, Ramey E, Ramwell P (1983) Glucocorticoid protection against PAF-acether toxicity in mice. Br J Pharmacol 79:595

    PubMed  Google Scholar 

  18. O'Flaherty JT, Wykle RL, Miller CH, Lewis JC, Waite M, Bass DA, McCall CE, DeChatelet LR (1981) 1-0-alkyl-sn-glyceryl-3-phosphorylcholines: a novel class of neutrophil stimulants. Am J Pathol 103:70

    PubMed  Google Scholar 

  19. Ogletree ML, Lefer AM (1976) Influence of nonsteroidal anti-inflammatory agents on myocardial ischemia. J Pharmacol Exp Therap 197:582

    Google Scholar 

  20. Prevost MC, Cariven C, Simon MF, Chap H, Douste-Blazy L (1984) Platelet activating factor (PAF-acether) is released into rat pulmonary alveolar fluid as a consequence of hypoxia. Biochem Biophys Res Commun 119:58

    PubMed  Google Scholar 

  21. Rosalki SB (1967) Improved procedure for creatine phosphokinase determination. J Lab Clin Med 69:696

    PubMed  Google Scholar 

  22. Smith III EF, Lefer AM, Aharony D, Smith JB, Magolda RL, Claremon D, Nicolaou KC (1981) Carbocyclic thromboxane A2: Aggravation of myocardial ischemia by a new synthetic thromboxane A2 analog. Prostaglandins 21:443

    PubMed  Google Scholar 

  23. Smith JB, Burke SE, Lefer AM, Freilich A (1984) Continuous measurements of ATP secretion in vivo. Pharmaceut Res 1:40

    Google Scholar 

  24. Vargaftig BB, Lefort J, Chignard M, Benveniste J (1980) Platelet activating factor induces a platelet-dependent bronchoconstriction unrelated to the formation of prostaglandin derivatives. Europ J Pharmacol 65:185

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported in part by Research Grant No. HL-5565 from the National Heart, Lung and Blood Institute of the NIH.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leprán, I., Lefer, A.M. Ischemia aggravating effects of platelet-activating factor in acute myocardial ischemia. Basic Res Cardiol 80, 135–141 (1985). https://doi.org/10.1007/BF01910460

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01910460

Key words

Navigation