Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Jan;93(1):188–194. doi: 10.1172/JCI116944

Platelet-activating factor causes ventilation-perfusion mismatch in humans.

R Rodriguez-Roisin 1, M A Félez 1, K F Chung 1, J A Barberà 1, P D Wagner 1, A Cobos 1, P J Barnes 1, J Roca 1
PMCID: PMC293752  PMID: 8282786

Abstract

We hypothesized that platelet-activating factor (PAF), a potent inflammatory mediator, could induce gas exchange abnormalities in normal humans. To this end, the effect of aerosolized PAF (2 mg/ml solution; 24 micrograms) on ventilation-perfusion (VA/Q) relationships, hemodynamics, and resistance of the respiratory system was studied in 14 healthy, nonatopic, and nonsmoking individuals (23 +/- 1 [SEM]yr) before and at 2, 4, 6, 8, 15, and 45 min after inhalation, and compared to that of inhaled lyso-PAF in 10 other healthy individuals (24 +/- 2 yr). PAF induced, compared to lyso-PAF, immediate leukopenia (P < 0.001) followed by a rebound leukocytosis (P < 0.002), increased minute ventilation (P < 0.05) and resistance of the respiratory system (P < 0.01), and decreased systemic arterial pressure (P < 0.05). Similarly, compared to lyso-PAF, PaO2 showed a trend to fall (by 12.2 +/- 4.3 mmHg, mean +/- SEM maximum change from baseline), and arterial-alveolar O2 gradient increased (by 16.7 +/- 4.3 mmHg) (P < 0.02) after PAF, because of VA/Q mismatch: the dispersion of pulmonary blood flow and that of ventilation increased by 0.45 +/- 0.1 (P < 0.01) and 0.29 +/- 0.1 (P < 0.04), respectively. We conclude that in normal subjects, inhaled PAF results in considerable immediate VA/Q inequality and gas exchange impairment. These results reinforce the notion that PAF may play a major role as a mediator of inflammation in the human lung.

Full text

PDF
194

Images in this article

191Image
on p.191
191Image
on p.191
191Image
on p.191
191Image
on p.191
191Image
on p.191
191Image
on p.191

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ballester E., Roca J., Ramis L., Wagner P. D., Rodriguez-Roisin R. Pulmonary gas exchange in severe chronic asthma. Response to 100% oxygen and salbutamol. Am Rev Respir Dis. 1990 Mar;141(3):558–562. doi: 10.1164/ajrccm/141.3.558. [DOI] [PubMed] [Google Scholar]
  2. Burhop K. E., Garcia J. G., Selig W. M., Lo S. K., van der Zee H., Kaplan J. E., Malik A. B. Platelet-activating factor increases lung vascular permeability to protein. J Appl Physiol (1985) 1986 Dec;61(6):2210–2217. doi: 10.1152/jappl.1986.61.6.2210. [DOI] [PubMed] [Google Scholar]
  3. Burhop K. E., van der Zee H., Bizios R., Kaplan J. E., Malik A. B. Pulmonary vascular response to platelet-activating factor in awake sheep and the role of cyclooxygenase metabolites. Am Rev Respir Dis. 1986 Sep;134(3):548–554. doi: 10.1164/arrd.1986.134.3.548. [DOI] [PubMed] [Google Scholar]
  4. Christman B. W., Lefferts P. L., King G. A., Snapper J. R. Role of circulating platelets and granulocytes in PAF-induced pulmonary dysfunction in awake sheep. J Appl Physiol (1985) 1988 May;64(5):2033–2041. doi: 10.1152/jappl.1988.64.5.2033. [DOI] [PubMed] [Google Scholar]
  5. Chung K. F., Barnes P. J. Effects of platelet activating factor on airway calibre, airway responsiveness, and circulating cells in asthmatic subjects. Thorax. 1989 Feb;44(2):108–115. doi: 10.1136/thx.44.2.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chung K. F., Dent G., Barnes P. J. Effects of salbutamol on bronchoconstriction, bronchial hyperresponsiveness, and leucocyte responses induced by platelet activating factor in man. Thorax. 1989 Feb;44(2):102–107. doi: 10.1136/thx.44.2.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chung K. F. Platelet-activating factor in inflammation and pulmonary disorders. Clin Sci (Lond) 1992 Aug;83(2):127–138. doi: 10.1042/cs0830127. [DOI] [PubMed] [Google Scholar]
  8. Cuss F. M., Dixon C. M., Barnes P. J. Effects of inhaled platelet activating factor on pulmonary function and bronchial responsiveness in man. Lancet. 1986 Jul 26;2(8500):189–192. doi: 10.1016/s0140-6736(86)92489-x. [DOI] [PubMed] [Google Scholar]
  9. Denjean A., Arnoux B., Masse R., Lockhart A., Benveniste J. Acute effects of intratracheal administration of platelet-activating factor in baboons. J Appl Physiol Respir Environ Exerc Physiol. 1983 Sep;55(3):799–804. doi: 10.1152/jappl.1983.55.3.799. [DOI] [PubMed] [Google Scholar]
  10. Evans J. W., Wagner P. D. Limits on VA/Q distributions from analysis of experimental inert gas elimination. J Appl Physiol Respir Environ Exerc Physiol. 1977 Jun;42(6):889–898. doi: 10.1152/jappl.1977.42.6.889. [DOI] [PubMed] [Google Scholar]
  11. Evans T. W., Chung K. F., Rogers D. F., Barnes P. J. Effect of platelet-activating factor on airway vascular permeability: possible mechanisms. J Appl Physiol (1985) 1987 Aug;63(2):479–484. doi: 10.1152/jappl.1987.63.2.479. [DOI] [PubMed] [Google Scholar]
  12. Gale G. E., Torre-Bueno J. R., Moon R. E., Saltzman H. A., Wagner P. D. Ventilation-perfusion inequality in normal humans during exercise at sea level and simulated altitude. J Appl Physiol (1985) 1985 Mar;58(3):978–988. doi: 10.1152/jappl.1985.58.3.978. [DOI] [PubMed] [Google Scholar]
  13. Halonen M., Palmer J. D., Lohman I. C., McManus L. M., Pinckard R. N. Respiratory and circulatory alterations induced by acetyl glyceryl ether phosphorylcholine, a mediator of IgE anaphylaxis in the rabbit. Am Rev Respir Dis. 1980 Dec;122(6):915–924. doi: 10.1164/arrd.1980.122.6.915. [DOI] [PubMed] [Google Scholar]
  14. Humphrey D. M., McManus L. M., Hanahan D. J., Pinckard R. N. Morphologic basis of increased vascular permeability induced by acetyl glyceryl ether phosphorylcholine. Lab Invest. 1984 Jan;50(1):16–25. [PubMed] [Google Scholar]
  15. Johnson P. R., Black J. L., Armour C. L. Platelet-activating factor-induced contraction of human isolated bronchus. Eur Respir J. 1992 Sep;5(8):970–974. [PubMed] [Google Scholar]
  16. Laurindo F. R., Goldstein R. E., Davenport N. J., Ezra D., Feuerstein G. Z. Mechanisms of hypotension produced by platelet-activating factor. J Appl Physiol (1985) 1989 Jun;66(6):2681–2690. doi: 10.1152/jappl.1989.66.6.2681. [DOI] [PubMed] [Google Scholar]
  17. Matthews J. N., Altman D. G., Campbell M. J., Royston P. Analysis of serial measurements in medical research. BMJ. 1990 Jan 27;300(6719):230–235. doi: 10.1136/bmj.300.6719.230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McMurtry I. F., Morris K. G. Platelet-activating factor causes pulmonary vasodilation in the rat. Am Rev Respir Dis. 1986 Oct;134(4):757–762. doi: 10.1164/arrd.1986.134.4.757. [DOI] [PubMed] [Google Scholar]
  19. Mojarad M., Hamasaki Y., Said S. I. Platelet-activating factor increases pulmonary microvascular permeability and induces pulmonary edema. A preliminary report. Bull Eur Physiopathol Respir. 1983 May-Jun;19(3):253–256. [PubMed] [Google Scholar]
  20. Mélot C., Naeije R., Hallemans R., Lejeune P., Mols P. Hypoxic pulmonary vasoconstriction and pulmonary gas exchange in normal man. Respir Physiol. 1987 Apr;68(1):11–27. doi: 10.1016/0034-5687(87)90073-9. [DOI] [PubMed] [Google Scholar]
  21. Ralph D. D., Ott S. M., Sherrard D. J., Hlastala M. P. Inert gas analysis of ventilation-perfusion matching during hemodialysis. J Clin Invest. 1984 May;73(5):1385–1391. doi: 10.1172/JCI111342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roca J., Sanchis J., Agusti-Vidal A., Segarra F., Navajas D., Rodriguez-Roisin R., Casan P., Sans S. Spirometric reference values from a Mediterranean population. Bull Eur Physiopathol Respir. 1986 May-Jun;22(3):217–224. [PubMed] [Google Scholar]
  23. Rodriguez-Roisin R., Ballester E., Roca J., Torres A., Wagner P. D. Mechanisms of hypoxemia in patients with status asthmaticus requiring mechanical ventilation. Am Rev Respir Dis. 1989 Mar;139(3):732–739. doi: 10.1164/ajrccm/139.3.732. [DOI] [PubMed] [Google Scholar]
  24. Rodriguez-Roisin R., Ferrer A., Navajas D., Agusti A. G., Wagner P. D., Roca J. Ventilation-perfusion mismatch after methacholine challenge in patients with mild bronchial asthma. Am Rev Respir Dis. 1991 Jul;144(1):88–94. doi: 10.1164/ajrccm/144.1.88. [DOI] [PubMed] [Google Scholar]
  25. Rodriguez-Roisin R., Roca J., Agusti A. G., Mastai R., Wagner P. D., Bosch J. Gas exchange and pulmonary vascular reactivity in patients with liver cirrhosis. Am Rev Respir Dis. 1987 May;135(5):1085–1092. doi: 10.1164/arrd.1987.135.5.1085. [DOI] [PubMed] [Google Scholar]
  26. Rodriguez-Roisin R., Wagner P. D. Clinical relevance of ventilation-perfusion inequality determined by inert gas elimination. Eur Respir J. 1990 Apr;3(4):469–482. [PubMed] [Google Scholar]
  27. Romaldini H., Rodriguez-Roisin R., Lopez F. A., Ziegler T. W., Bencowitz H. Z., Wagner P. D. The mechanisms of arterial hypoxemia during hemodialysis. Am Rev Respir Dis. 1984 May;129(5):780–784. doi: 10.1164/arrd.1984.129.5.780. [DOI] [PubMed] [Google Scholar]
  28. Rubin A. H., Smith L. J., Patterson R. The bronchoconstrictor properties of platelet-activating factor in humans. Am Rev Respir Dis. 1987 Nov;136(5):1145–1151. doi: 10.1164/ajrccm/136.5.1145. [DOI] [PubMed] [Google Scholar]
  29. Schellenberg R. R. Airway responses to platelet-activating factor. Am Rev Respir Dis. 1987 Oct;136(4 Pt 2):S28–S32. doi: 10.1164/ajrccm/136.4_Pt_2.S28. [DOI] [PubMed] [Google Scholar]
  30. Shaw J. O., Pinckard R. N., Ferrigni K. S., McManus L. M., Hanahan D. J. Activation of human neutrophils with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glycerol-3-phosphorylcholine (platelet activating factor). J Immunol. 1981 Sep;127(3):1250–1255. [PubMed] [Google Scholar]
  31. Tam F. W., Clague J., Dixon C. M., Stuttle A. W., Henderson B. L., Peters A. M., Lavender J. P., Ind P. W. Inhaled platelet-activating factor causes pulmonary neutrophil sequestration in normal humans. Am Rev Respir Dis. 1992 Oct;146(4):1003–1008. doi: 10.1164/ajrccm/146.4.1003. [DOI] [PubMed] [Google Scholar]
  32. Tokuyama K., Lötvall J. O., Barnes P. J., Chung K. F. Mechanism of airway narrowing caused by inhaled platelet-activating factor. Role of airway microvascular leakage. Am Rev Respir Dis. 1991 Jun;143(6):1345–1349. doi: 10.1164/ajrccm/143.6.1345. [DOI] [PubMed] [Google Scholar]
  33. Wagner P. D., Gale G. E., Moon R. E., Torre-Bueno J. R., Stolp B. W., Saltzman H. A. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol (1985) 1986 Jul;61(1):260–270. doi: 10.1152/jappl.1986.61.1.260. [DOI] [PubMed] [Google Scholar]
  34. Wagner P. D., Hedenstierna G., Bylin G. Ventilation-perfusion inequality in chronic asthma. Am Rev Respir Dis. 1987 Sep;136(3):605–612. doi: 10.1164/ajrccm/136.3.605. [DOI] [PubMed] [Google Scholar]
  35. Wagner P. D., Rodriguez-Roisin R. Clinical advances in pulmonary gas exchange. Am Rev Respir Dis. 1991 Apr;143(4 Pt 1):883–888. doi: 10.1164/ajrccm/143.4_Pt_1.883. [DOI] [PubMed] [Google Scholar]
  36. Wagner P. D., Saltzman H. A., West J. B. Measurement of continuous distributions of ventilation-perfusion ratios: theory. J Appl Physiol. 1974 May;36(5):588–599. doi: 10.1152/jappl.1974.36.5.588. [DOI] [PubMed] [Google Scholar]
  37. Wardlaw A. J., Chung K. F., Moqbel R., MacDonald A. J., Hartnell A., McCusker M., Collins J. V., Barnes P. J., Kay A. B. Effects of inhaled PAF in humans on circulating and bronchoalveolar lavage fluid neutrophils. Relationship to bronchoconstriction and changes in airway responsiveness. Am Rev Respir Dis. 1990 Feb;141(2):386–392. doi: 10.1164/ajrccm/141.2.386. [DOI] [PubMed] [Google Scholar]
  38. Wardlaw A. J., Moqbel R., Cromwell O., Kay A. B. Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils. J Clin Invest. 1986 Dec;78(6):1701–1706. doi: 10.1172/JCI112765. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES