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. 1982 Sep;70(3):536–541. doi: 10.1172/JCI110645

Ibuprofen in canine endotoxin shock.

E R Jacobs, M E Soulsby, R C Bone, F J Wilson Jr, F C Hiller
PMCID: PMC370254  PMID: 7107893

Abstract

The participation of prostaglandins in the physiologic alterations of endotoxin shock has been well established with the aid of prostaglandin synthetase inhibitors. Our study was designed to investigate the potential of ibuprofen, a highly specific cyclooxygenase inhibitor, to reverse the hemodynamic and acid base abnormalities of canine endotoxin shock. Mean blood pressure fell to 49.8 +/- 6.6 mm Hg in dogs given endotoxin by 5 min after injection, and remained below 83 mm Hg for the duration of the 120-min observation period. In animals given endotoxin followed by ibuprofen, a similar initial drop of systemic blood pressure was seen, but it subsequently recovered to 150.2 +/- 4.1 mm Hg by 120 min (P less than 0.001). Cardiac index increased in animals given ibuprofen (2.3 +/- 0.28 liter/m2 per min) compared with animals given endotoxin alone (1.0 +/- 0.09 liter/m2 per min) by termination of the experiment. The arterial pH dropped in endotoxin treated animals to 7.18 +/- 0.03 by 120 min. Ibuprofen prevented the acidosis, the final pH in ibuprofen and endotoxin treated animals measuring 7.36 +/- 0.01. We conclude that ibuprofen protects against the hypotension, acidosis, and depression of cardiac index of canine endotoxin shock.

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Selected References

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

  1. Anderson F. L., Jubiz W., Tsagaris T. J., Kuida H. Endotoxin-induced prostaglandin E and F release in dogs. Am J Physiol. 1975 Feb;228(2):410–414. doi: 10.1152/ajplegacy.1975.228.2.410. [DOI] [PubMed] [Google Scholar]
  2. Baris C., Guest M. M., Frazer M. E. Direct effects of endotoxin on the microcirculation. Adv Shock Res. 1980;4:153–160. [PubMed] [Google Scholar]
  3. Brown K. A., Collins A. J. Action of nonsteroidal, anti-inflammatory drugs on human and rat peripheral leucocyte migration in vitro. Ann Rheum Dis. 1977 Jun;36(3):239–243. doi: 10.1136/ard.36.3.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cook J. A., Wise W. C., Halushka P. V. Elevated thromboxane levels in the rat during endotoxic shock: protective effects of imidazole, 13-azaprostanoic acid, or essential fatty acid deficiency. J Clin Invest. 1980 Jan;65(1):227–230. doi: 10.1172/JCI109655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Craddock P. R., Hammerschmidt D., White J. G., Dalmosso A. P., Jacob H. S. Complement (C5-a)-induced granulocyte aggregation in vitro. A possible mechanism of complement-mediated leukostasis and leukopenia. J Clin Invest. 1977 Jul;60(1):260–264. doi: 10.1172/JCI108763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Demling R. H., Proctor R., Duy N., Starling J. R. Lung lysosomal enzyme release during hemorrhagic shock and endotoxemia. J Surg Res. 1980 Mar;28(3):269–279. doi: 10.1016/0022-4804(80)90126-2. [DOI] [PubMed] [Google Scholar]
  7. Demling R. H., Smith M., Gunther R., Flynn J. T., Gee M. H. Pulmonary injury and prostaglandin production during endotoxemia in conscious sheep. Am J Physiol. 1981 Mar;240(3):H348–H353. doi: 10.1152/ajpheart.1981.240.3.H348. [DOI] [PubMed] [Google Scholar]
  8. Demling R. H., Smith M., Gunther R., Gee M., Flynn J. The effect of prostacyclin infusion on endotoxin-induced lung injury. Surgery. 1981 Feb;89(2):257–263. [PubMed] [Google Scholar]
  9. Fletcher J. R., Ramwell P. W. Indomethacin treatment following baboon endotoxin shock improves survival. Adv Shock Res. 1980;4:103–111. [PubMed] [Google Scholar]
  10. Fletcher J. R., Ramwell P. W. Modification, by aspirin and indomethacin, of the haemodynamic and prostaglandin releasing effects of E. coli endotoxin in the dog. Br J Pharmacol. 1977 Oct;61(2):175–181. doi: 10.1111/j.1476-5381.1977.tb08402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fletcher J. R., Ramwell P. W. Prostaglandins in shock: to give or to block? Adv Shock Res. 1980;3:57–66. [PubMed] [Google Scholar]
  12. Goldstein R. E., Davenport N. J., Capurro N. L., Lipson L. C., Bonow R. O., Shulman N. R., Epstein S. E. Relative effects of sulfinpyrazone and ibuprofen on canine platelet function and prostaglandin-mediated coronary vasodilation. J Cardiovasc Pharmacol. 1980 Jul-Aug;2(4):399–409. doi: 10.1097/00005344-198007000-00007. [DOI] [PubMed] [Google Scholar]
  13. Higgs G. A., Eakins K. E., Mugridge K. G., Moncada S., Vane J. R. The effects of non-steroid anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation. Eur J Pharmacol. 1980 Aug 22;66(1):81–86. doi: 10.1016/0014-2999(80)90297-6. [DOI] [PubMed] [Google Scholar]
  14. Hinshaw L. B., Solomon L. A., Erdös E. G., Reins D. A., Gunter B. J. Effects of acetylsalicylic acid on the canine response to endotoxin. J Pharmacol Exp Ther. 1967 Sep;157(3):665–671. [PubMed] [Google Scholar]
  15. Holaday J. W., Faden A. I. Naloxone reversal of endotoxin hypotension suggests role of endorphins in shock. Nature. 1978 Oct 5;275(5679):450–451. doi: 10.1038/275450a0. [DOI] [PubMed] [Google Scholar]
  16. Hosea S., Brown E., Hammer C., Frank M. Role of complement activation in a model of adult respiratory distress syndrome. J Clin Invest. 1980 Aug;66(2):375–382. doi: 10.1172/JCI109866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hsu C. C., Wu S. J., Celic L., Weaver L. J., Solliday N. Increased proportion of active sheep erythrocyte rosette-forming lymphocytes and plasma rosette enhancement in sarcoidosis. Am Rev Respir Dis. 1979 Mar;119(3):383–389. doi: 10.1164/arrd.1979.119.3.383. [DOI] [PubMed] [Google Scholar]
  18. Lefer A. M., Polansky E. W. Beneficial effects of ibuprofen in acute myocardial ischemia. Cardiology. 1979;64(5):265–279. doi: 10.1159/000170624. [DOI] [PubMed] [Google Scholar]
  19. Nakanishi M., Goto K., Hisadome M. [Studies on anti-inflammatory agents. XXIX. Inhibitory effects of Tinoridine on release of lysosome enzymes and lipid peroxidation in rat liver (author's transl)]. Yakugaku Zasshi. 1975 Aug;95(8):936–943. doi: 10.1248/yakushi1947.95.8_936. [DOI] [PubMed] [Google Scholar]
  20. Parker J. L., Adams H. R. Myocardial effects of endotoxin shock: characterization of an isolated heart muscle model. Adv Shock Res. 1979;2:163–175. [PubMed] [Google Scholar]
  21. Parratt J. R., Sturgess R. M. The possible roles of histamine, 5-hydroxytryptamine and prostaglandin F2alpha as mediators of the acute pulmonary effects of endotoxin. Br J Pharmacol. 1977 Jun;60(2):209–219. doi: 10.1111/j.1476-5381.1977.tb07743.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sibbald W., Peters S., Lindsay R. M. Serotonin and pulmonary hypertension in human septic ARDS. Crit Care Med. 1980 Sep;8(9):490–494. doi: 10.1097/00003246-198009000-00003. [DOI] [PubMed] [Google Scholar]
  23. Smith E. F., 3rd, Tabas J. H., Lefer A. M. Beneficial actions of imidazole in endotoxin shock. Prostaglandins Med. 1980 Apr;4(4):215–225. doi: 10.1016/0161-4630(80)90016-6. [DOI] [PubMed] [Google Scholar]
  24. Soulsby M. E., Bennett C. L., Hess M. L. Canine arterial calcium transport during endotoxin shock. Circ Shock. 1980;7(2):139–148. [PubMed] [Google Scholar]
  25. Stein M., Thomas D. P. Role of platelets in the acute pulmonary responses to endotoxin. J Appl Physiol. 1967 Jul;23(1):47–52. doi: 10.1152/jappl.1967.23.1.47. [DOI] [PubMed] [Google Scholar]
  26. Weissmann G., Dukor P., Zurier R. B. Effect of cyclic AMP on release of lysosomal enzymes from phagocytes. Nat New Biol. 1971 Jun 2;231(22):131–135. doi: 10.1038/newbio231131a0. [DOI] [PubMed] [Google Scholar]
  27. Zimmerman B. G., Ryan M. J., Gomer S., Kraft E. Effect of the prostaglandin synthesis inhibitors indomethacin and eicosa-5,8,11,14-tetraynoic acid on adrenergic responses in dog cutaneous vasculature. J Pharmacol Exp Ther. 1973 Nov;187(2):315–323. [PubMed] [Google Scholar]

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