Logo of annsurgLink to Publisher's site
Ann Surg. 1984 Nov; 200(5): 619–626.
PMCID: PMC1250546

Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis.


This study investigates the role of prostaglandins (PG) in hyperdynamic sepsis. Thirteen chronically instrumented dogs were rendered septic by implanting in the peritoneal cavity a fibrin clot containing viable Escherichia coli. One day later, cardiac output (CO) increased from 2.80 +/- 0.22 to 3.72 +/- 0.32 l/min (p = 0.011); heart rate (HR) increased from 122 +/- 8 to 147 +/- 6 beats/min (p = 0.005); mean pulmonary artery pressure (PAP) increased from 15 +/- 1 to 19 +/- 1 mmHg (p = 0.003); mean systemic arterial pressure (MAP) decreased from 120 +/- 5 to 107 +/- 7 mmHg; and systemic vascular resistance (SVR) decreased from 44.1 +/- 2.6 to 29.3 +/- 1.9 mmHg/l/min (p less than 0.001). Sixty minutes after intravenous injection of indomethacin (2 mg/kg) or ibuprofen (25 mg/kg), CO decreased to 2.60 +/- 0.21 l/min (p less than 0.001); HR decreased to 118 +/- 5 beats/min (p less than 0.001); PAP decreased to 17 +/- 1 mmHg (p = 0.021); and SVR increased to 43.7 mmHg/l/min (p less than 0.001). In seven control dogs, laparotomy alone did not significantly affect any of these parameters. Infusion of indomethacin caused a slight increase in MAP (106 +/- 4 to 116 +/- 4 mmHg, p = 0.035) but otherwise did not alter hemodynamics. It is concluded that administration of indomethacin or ibuprofen restores normal hemodynamics in a canine model of high-output sepsis, probably by inhibiting PG synthesis.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Cook JA, Wise WC, Halushka PV. 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. [PMC free article] [PubMed]
  • Anderson FL, Jubiz W, Tsagaris TJ, Kuida H. Endotoxin-induced prostaglandin E and F release in dogs. Am J Physiol. 1975 Feb;228(2):410–414. [PubMed]
  • Anderson FL, Tsagaris TJ, Jubiz W, Kuida H. Prostaglandin F and E levels during endotoxin-induced pulmonary hypertension in calves. Am J Physiol. 1975 May;228(5):1479–1482. [PubMed]
  • Coker SJ, Hughes B, Parratt JR, Rodger IW, Zeitlin IJ. The release of prostanoids during the acute pulmonary response to E. coli endotoxin in anaesthetized cats. Br J Pharmacol. 1983 Mar;78(3):561–570. [PMC free article] [PubMed]
  • Casey LC, Fletcher JR, Zmudka MI, Ramwell PW. Prevention of endotoxin-induced pulmonary hypertension in primates by the use of a selective thromboxane synthetase inhibitor, OKY 1581. J Pharmacol Exp Ther. 1982 Aug;222(2):441–446. [PubMed]
  • Fletcher JR, Ramwell PW. E. coli endotoxin shock in the dog; treatment with lidocaine or indomethacin. Br J Pharmacol. 1978 Oct;64(2):185–191. [PMC free article] [PubMed]
  • Fletcher JR, Ramwell PW. Lidocaine or indomethacin improves survival in baboon endotoxin shock. J Surg Res. 1978 Mar;24(3):154–160. [PubMed]
  • Short BL, Gardiner M, Walker RI, Jones SR, Fletcher JR. Indomethacin improves survival in gram-negative sepsis. Adv Shock Res. 1981;6:27–36. [PubMed]
  • Wichterman KA, Baue AE, Chaudry IH. Sepsis and septic shock--a review of laboratory models and a proposal. J Surg Res. 1980 Aug;29(2):189–201. [PubMed]
  • Brown PP, Coalson JJ, Elkins RC, Hinshaw LB, Greenfield LJ. Hemodynamic and respiratory responses of conscious swine to E. coli endotoxin. J Trauma. 1976 Mar;16(3):184–190. [PubMed]
  • Somani P, Saini RK. A comparison of the cardiovascular, renal, and coronary effects of dopamine and monensin in endotoxic shock. Circ Shock. 1981;8(4):451–464. [PubMed]
  • Cohn JD, Greenspan M, Goldstein CR, Gudwin AL, Siegel JH, DelGuercio LR. Arteriovenous shunting in high cardiac output shcok syndromes. Surg Gynecol Obstet. 1968 Aug;127(2):282–288. [PubMed]
  • Finley RJ, Duff JH, Holliday RL, Jones D, Marchuk JB. Capillary muscle blood flow in human sepsis. Surgery. 1975 Jul;78(1):87–94. [PubMed]
  • Nishijima H, Weil MH, Shubin H, Cavanilles J. Hemodynamic and metabolic studies on shock associated with gram negative bacteremia. Medicine (Baltimore) 1973 Jul;52(4):287–294. [PubMed]
  • Fink MP, MacVittie TJ, Casey LC. Effects of nonsteroidal anti-inflammatory drugs on renal function in septic dogs. J Surg Res. 1984 May;36(5):516–525. [PubMed]
  • Rossing RG, Cain SM. A nomogram relating pO2, pH, temperature, and hemoglobin saturation in the dog. J Appl Physiol. 1966 Jan;21(1):195–201. [PubMed]
  • Ahrenholz DH, Simmons RL. Fibrin in peritonitis. I. Beneficial and adverse effects of fibrin in experimental E. coli peritonitis. Surgery. 1980 Jul;88(1):41–47. [PubMed]
  • Cronenwett JL, Lindenauer SM. Hemodynamic effects of cecal ligation sepsis in dogs. J Surg Res. 1982 Oct;33(4):324–331. [PubMed]
  • Carroll GC, Snyder JV. Hyperdynamic severe intravascular sepsis depends on fluid administration in cynomolgus monkey. Am J Physiol. 1982 Jul;243(1):R131–R141. [PubMed]
  • Clowes GH, Jr, O'Donnell TF, Jr, Ryan NT, Blackburn GL. Energy metabolism in sepsis: treatment based on different patterns in shock and high output stage. Ann Surg. 1974 May;179(5):684–696. [PMC free article] [PubMed]
  • Zambraski EJ, Dunn MJ. Renal prostaglandin E2 secretion and excretion in conscious dogs. Am J Physiol. 1979 Jun;236(6):F552–F558. [PubMed]
  • Dunn MJ, Zambraski EJ. Renal effects of drugs that inhibit prostaglandin synthesis. Kidney Int. 1980 Nov;18(5):609–622. [PubMed]
  • Groves AC, Griffiths J, Leung F, Meek RN. Plasma catecholamines in patients with serious postoperative infection. Ann Surg. 1973 Jul;178(1):102–107. [PMC free article] [PubMed]
  • Dahn M, Bouwman D, Kirkpatrick J. The sepsis-glucose intolerance riddle: a hormonal explanation. Surgery. 1979 Sep;86(3):423–428. [PubMed]
  • Sugerman HJ, Austin G, Newsome HH, Hylemon P, Greenfield LJ. Hemodynamics, oxygen consumption and serum catecholamine changes in progressive, lethal peritonitis in the dog. Surg Gynecol Obstet. 1982 Jan;154(1):8–12. [PubMed]
  • Bravo EL, Tarazi RC. Plasma catecholamines in clinical investigation: a useful index or a meaningless number? J Lab Clin Med. 1982 Aug;100(2):155–160. [PubMed]
  • Hedqvist P. Studies on the effect of prostaglandins E1 and E2 on the sympathetic neuromuscular transmission in some animal tissues. Acta Physiol Scand Suppl. 1970;345:1–40. [PubMed]
  • Lonigro AJ, Terragno NA, Malik KU, McGiff JC. Differential inhibition by prostaglandins of the renal actions of pressor stimuli. Prostaglandins. 1973 May;3(5):595–606. [PubMed]
  • Malik KU. Prostaglandin-mediated inhibition of the vasoconstrictor responses of the isolated perfused art splenic vasculature to adrenergic stimuli. Circ Res. 1978 Aug;43(2):225–233. [PubMed]
  • Dusting GJ, Moncada S, Vane JR. Recirculation of prostacyclin (PGI2) in the dog. Br J Pharmacol. 1978 Oct;64(2):315–320. [PMC free article] [PubMed]
  • Fitzpatrick TM, Alter I, Corey EJ, Ramwell PW, Rose JC, Kot PA. Cardiovascular responses to PGI2 (prostacyclin) in the dog. Circ Res. 1978 Feb;42(2):192–194. [PubMed]
  • Chapple DJ, Dusting GJ, Hughes R, Vane JR. Some direct and reflex cardiovascular actions of prostacyclin (PGI2) and prostaglandin E2 in anaesthetized dogs. Br J Pharmacol. 1980 Mar;68(3):437–447. [PMC free article] [PubMed]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...