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. 1984 Nov;74(5):1782–1791. doi: 10.1172/JCI111597

Effects of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia.

J R Snapper, J M Hinson Jr, A A Hutchison, P L Lefferts, M L Ogletree, K L Brigham
PMCID: PMC425358  PMID: 6501570

Abstract

The effect of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia was studied in eight unanesthetized sheep. Platelets were depleted with rabbit anti-sheep platelet antibodies (APA). Bolus injections of APA alone caused marked pulmonary hypertension (PPA increased from 21 +/- 2 to 62 +/- 5 cm H2O +/- SE) and alterations in lung mechanics (dynamic compliance of the lung [Cdyn] decreased to 38.5 +/- 4.6% and resistance to air flow across the lung [RL] increased to 705 +/- 162% +/- SE of control), which were attenuated by pretreatment with meclofenamate. It was possible to deplete platelets before endotoxemia through a slow continuous infusion of APA without altering base-line values of the measured variables. Platelet depletion did not significantly attenuate the alterations in pulmonary hemodynamics, lung mechanics, lung fluid and solute exchange, or the normal increase in lung lymph concentrations of thromboxane B2 or 6-keto-PGF1 alpha observed following endotoxemia in the sheep. We conclude that normal circulating platelet counts are not required for the full expression of the sheep's response to endotoxemia.

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Selected References

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

  1. Addonizio V. P., Jr, Edmunds L. H., Jr, Colman R. W. The function of monkey (M. mulatta) platelets compared to platelets of pig, sheep, and man. J Lab Clin Med. 1978 Jun;91(6):989–997. [PubMed] [Google Scholar]
  2. Binder A. S., Kageler W., Perel A., Flick M. R., Staub N. C. Effect of platelet depletion on lung vascular permeability after microemboli in sheep. J Appl Physiol Respir Environ Exerc Physiol. 1980 Mar;48(3):414–420. doi: 10.1152/jappl.1980.48.3.414. [DOI] [PubMed] [Google Scholar]
  3. Bredenberg C. E., Taylor G. A., Webb W. R. The effect of thrombocytopenia on the pulmonary and systemic hemodynamics of canine endotoxin shock. Surgery. 1980 Jan;87(1):59–68. [PubMed] [Google Scholar]
  4. Brigham K. L., Bowers R. E., McKeen C. R. Methylprednisolone prevention of increased lung vascular permeability following endotoxemia in sheep. J Clin Invest. 1981 Apr;67(4):1103–1110. doi: 10.1172/JCI110123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brigham K. L., Bowers R., Haynes J. Increased sheep lung vascular permeability caused by Escherichia coli endotoxin. Circ Res. 1979 Aug;45(2):292–297. doi: 10.1161/01.res.45.2.292. [DOI] [PubMed] [Google Scholar]
  6. Burke S. E., Lefer A. M., Nicolaou K. C., Smith G. M., Smith J. B. Responsiveness of platelets and coronary arteries from different species to synthetic thromboxane and prostaglandin endoperoxide analogues. Br J Pharmacol. 1983 Feb;78(2):287–292. doi: 10.1111/j.1476-5381.1983.tb09393.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Corash L., Tan H., Gralnick H. R. Heterogeneity of human whole blood platelet subpopulations. I. Relationship between buoyant density, cell volume, and ultrastructure. Blood. 1977 Jan;49(1):71–87. [PubMed] [Google Scholar]
  8. DUBOIS A. B., BOTELHO S. Y., BEDELL G. N., MARSHALL R., COMROE J. H., Jr A rapid plethysmographic method for measuring thoracic gas volume: a comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects. J Clin Invest. 1956 Mar;35(3):322–326. doi: 10.1172/JCI103281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Esbenshade A. M., Newman J. H., Lams P. M., Jolles H., Brigham K. L. Respiratory failure after endotoxin infusion in sheep: lung mechanics and lung fluid balance. J Appl Physiol Respir Environ Exerc Physiol. 1982 Oct;53(4):967–976. doi: 10.1152/jappl.1982.53.4.967. [DOI] [PubMed] [Google Scholar]
  10. Evensen S. A., Elgjo R. F. Antibody-induced platelet injury: its potency as a trigger of intravascular clotting. Scand J Haematol. 1972;9(1):61–72. doi: 10.1111/j.1600-0609.1972.tb00914.x. [DOI] [PubMed] [Google Scholar]
  11. Hechtman H. B., Lonergan E. A., Staunton H. P., Dennis R. C., Shepro D. Pulmonary entrapment of platelets during acute respiratory failure. Surgery. 1978 Mar;83(3):277–283. [PubMed] [Google Scholar]
  12. Heflin A. C., Jr, Brigham K. L. Prevention by granulocyte depletion of increased vascular permeability of sheep lung following endotoxemia. J Clin Invest. 1981 Nov;68(5):1253–1260. doi: 10.1172/JCI110371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hinson J. M., Jr, Hutchison A. A., Ogletree M. L., Brigham K. L., Snapper J. R. Effect of granulocyte depletion on altered lung mechanics after endotoxemia in sheep. J Appl Physiol Respir Environ Exerc Physiol. 1983 Jul;55(1 Pt 1):92–99. doi: 10.1152/jappl.1983.55.1.92. [DOI] [PubMed] [Google Scholar]
  14. Kovacs I. B., Caen J. P. Increased interaction of vascular endothelium and leucocytes after administration of antiplatelet serum: role in the developing vascular defect. J Clin Pathol. 1979 May;32(5):445–449. doi: 10.1136/jcp.32.5.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leach C. M., Thorburn G. D. A comparative study of collagen induced thromboxane release from platelets of different species: implications for human atherosclerosis models. Prostaglandins. 1982 Jul;24(1):47–59. doi: 10.1016/0090-6980(82)90176-9. [DOI] [PubMed] [Google Scholar]
  16. Martin B. A., Dahlby R., Nicholls I., Hogg J. C. Platelet sequestration in lung with hemorrhagic shock and reinfusion in dogs. J Appl Physiol Respir Environ Exerc Physiol. 1981 Jun;50(6):1306–1312. doi: 10.1152/jappl.1981.50.6.1306. [DOI] [PubMed] [Google Scholar]
  17. McDonald J. W., Ali M., Morgan E., Townsend E. R., Cooper J. D. Thromboxane synthesis by sources other than platelets in association with complement-induced pulmonary leukostasis and pulmonary hypertension in sheep. Circ Res. 1983 Jan;52(1):1–6. doi: 10.1161/01.res.52.1.1. [DOI] [PubMed] [Google Scholar]
  18. Meyers K. M., Katz J. B., Clemmons R. M., Smith J. B., Holmsen H. An evaluation of the arachidonate pathway of platelets from companion and food-producing animals, mink, and man. Thromb Res. 1980 Oct 1;20(1):13–24. doi: 10.1016/0049-3848(80)90052-3. [DOI] [PubMed] [Google Scholar]
  19. Meyrick B., Brigham K. L. Acute effects of Escherichia coli endotoxin on the pulmonary microcirculation of anesthetized sheep structure:function relationships. Lab Invest. 1983 Apr;48(4):458–470. [PubMed] [Google Scholar]
  20. Ogletree M. L., Brigham K. L. Effects of cyclooxygenase inhibitors on pulmonary vascular responses to endotoxin in unanesthetized sheep. Prostaglandins Leukot Med. 1982 May;8(5):489–502. [PubMed] [Google Scholar]
  21. Snapper J. R., Hutchison A. A., Ogletree M. L., Brigham K. L. Effects of cyclooxygenase inhibitors on the alterations in lung mechanics caused by endotoxemia in the unanesthetized sheep. J Clin Invest. 1983 Jul;72(1):63–76. doi: 10.1172/JCI110985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Staub N. C., Bland R. D., Brigham K. L., Demling R., Erdmann A. J., 3rd, Woolverton W. C. Preparation of chronic lung lymph fistulas in sheep. J Surg Res. 1975 Nov;19(5):315–320. doi: 10.1016/0022-4804(75)90056-6. [DOI] [PubMed] [Google Scholar]
  23. Vaage J. Intravascular platelet aggregation and pulmonary injury. Ann N Y Acad Sci. 1982;384:301–318. doi: 10.1111/j.1749-6632.1982.tb21380.x. [DOI] [PubMed] [Google Scholar]
  24. Williams F. E., Bellinger L. L., Frazier L. W. Short-term autonomic control in the cardiovascular system. Physiologist. 1981 Dec;24(6):53–55. [PubMed] [Google Scholar]
  25. Wonders T. R., Southmayd J. R., Schuette A. H., Huttemeier P. C., Kong D., Watkins W. D., Carvalho A., Zapol W. M. Reduced plasma thromboxane elevation during partial cardiopulmonary bypass in thrombocytopenic sheep. Trans Am Soc Artif Intern Organs. 1981;27:276–279. [PubMed] [Google Scholar]

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