Skip to main content
Top
Published in: BMC Infectious Diseases 1/2002

Open Access 01-12-2002 | Research article

Effects of Ibuprofen on the physiology and outcome of rabbit endotoxic shock

Authors: Ilhami Celik, Ayhan Akbulut, S Sirri Kilic, Ali Rahman, Pervin Vural, Mukaddes Canbaz, Suleyman Felek

Published in: BMC Infectious Diseases | Issue 1/2002

Login to get access

Abstract

Background

Despite major developments in the management of septic shock, the mortality rate had progressively increased. Ibuprofen has been shown to have beneficial physiological effects when used as a treatment. However, there are conflicting results with respect to survival. This study aims to investigate the effect of ibuprofen on vital functions, various physiological parameters and survival during endotoxic shock in rabbits.

Methods

Twenty-eight New Zealand rabbits were randomly separated into four groups. The first group received only saline, the second was given 2 mg/kg intravenous endotoxin at t0, the third received 30 mg/kg ibuprofen 30 minutes after endotoxin administration, whilst the fourth group received ibuprofen 30 minutes before the endotoxin. Respiratory and heart rate, mean arterial blood pressure and rectal temperature were recorded. Complete blood counts were performed and thromboxane B2 was measured every 30 minutes for the first two hours, and then hourly over the course of the experiment. Urine samples were collected at the same time points for the measurement of prostaglandin E2.

Results

Ibuprofen was found to improve respiratory rate, heart rate, and arterial pressure. However, it did not improve the negative effects of endotoxin on body temperature, haematocrit values, white blood cell count, and thrombocyte number. Thromboxane B2 levels in group IV were significantly lower than in the other groups, and the increase started at a later timepoint. In ibuprofen-treated animals, Prostaglandin E2 levels stayed low for at least 90 minutes, but started to rise thereafter. While the average survival in Group II animals was 192.9 ± 46.9 minutes, those of groups III and IV were 339.1 ± 33.5 minutes (p < 0.05) and 383.0 ± 39.6 minutes (p = 0.01), respectively.

Conclusions

Ibuprofen appears to increase survival in endotoxic shock-induced animals. Therefore, it may be helpful for the prophylaxis and treatment of patients with, or who are likely to develop, septic shock.
Appendix
Available only for authorised users
Literature
1.
go back to reference Hubbard JD, Janssen HF: Increased microvascular permeability in canine endotoxic shock: protective effects of ibuprofen. Circ Shock. 1988, 26 (2): 169-83.PubMed Hubbard JD, Janssen HF: Increased microvascular permeability in canine endotoxic shock: protective effects of ibuprofen. Circ Shock. 1988, 26 (2): 169-83.PubMed
2.
go back to reference Karima R, Matsumoto S, Higashi H: The molecular pathogenesis of endotoxic shock and organ failure. Mol Med Today. 1999, 5 (3): 123-32. 10.1016/S1357-4310(98)01430-0.CrossRefPubMed Karima R, Matsumoto S, Higashi H: The molecular pathogenesis of endotoxic shock and organ failure. Mol Med Today. 1999, 5 (3): 123-32. 10.1016/S1357-4310(98)01430-0.CrossRefPubMed
3.
go back to reference Fletcher JR: The effects of ibuprofen on eicosanoid synthesis in sepsis. Crit Care Med. 1999, 27 (4): 669-70.CrossRefPubMed Fletcher JR: The effects of ibuprofen on eicosanoid synthesis in sepsis. Crit Care Med. 1999, 27 (4): 669-70.CrossRefPubMed
4.
go back to reference Griffin MP, Gore DC, Lobe TE, Flynn JF, Traber DL, Herndon DN: Ibuprofen therapy in experimental porcine gram-negative septic shock. Resuscitation. 1991, 22 (1): 75-83.CrossRefPubMed Griffin MP, Gore DC, Lobe TE, Flynn JF, Traber DL, Herndon DN: Ibuprofen therapy in experimental porcine gram-negative septic shock. Resuscitation. 1991, 22 (1): 75-83.CrossRefPubMed
6.
go back to reference Fink MP, MacVittie TJ, Casey LC: Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis. Ann Surg. 1984, 200 (5): 619-26.CrossRefPubMedPubMedCentral Fink MP, MacVittie TJ, Casey LC: Inhibition of prostaglandin synthesis restores normal hemodynamics in canine hyperdynamic sepsis. Ann Surg. 1984, 200 (5): 619-26.CrossRefPubMedPubMedCentral
7.
go back to reference Hulton NR, Johnson DJ, Willmore DW: Limited effects of prostaglandin inhibitors in Escherichia coli sepsis. Surg. 1985, 98 (2): 291-7. Hulton NR, Johnson DJ, Willmore DW: Limited effects of prostaglandin inhibitors in Escherichia coli sepsis. Surg. 1985, 98 (2): 291-7.
8.
go back to reference Coran AG, Drongowski RA, Paik JJ, Remick DG: Ibuprofen intervention in canine septic shock: reduction of pathophysiology without decreased cytokines. J Surg Res. 1992, 53 (3): 272-9.CrossRefPubMed Coran AG, Drongowski RA, Paik JJ, Remick DG: Ibuprofen intervention in canine septic shock: reduction of pathophysiology without decreased cytokines. J Surg Res. 1992, 53 (3): 272-9.CrossRefPubMed
9.
go back to reference Herbertson M, Werner H, Studer W, Russell JA, Walley KR: Decreased left ventricular contractility during porcine endotoxemia is not prevented by ibuprofen. Crit Care Med. 1996, 24 (5): 815-9.CrossRefPubMed Herbertson M, Werner H, Studer W, Russell JA, Walley KR: Decreased left ventricular contractility during porcine endotoxemia is not prevented by ibuprofen. Crit Care Med. 1996, 24 (5): 815-9.CrossRefPubMed
10.
go back to reference Bernard GR, Wheeler AP, Russell JA, et al: The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med. 1997, 336 (13): 912-8. 10.1056/NEJM199703273361303.CrossRefPubMed Bernard GR, Wheeler AP, Russell JA, et al: The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med. 1997, 336 (13): 912-8. 10.1056/NEJM199703273361303.CrossRefPubMed
11.
go back to reference Northover BJ, Subramanian G: Analgesics-antipyretics drugs as antagonists of endotoxic shock in dogs. J Pathol Bacteriol. 1962, 83: 463-8.CrossRefPubMed Northover BJ, Subramanian G: Analgesics-antipyretics drugs as antagonists of endotoxic shock in dogs. J Pathol Bacteriol. 1962, 83: 463-8.CrossRefPubMed
13.
go back to reference Kopolovic R, Thrailkill KM, Martin DT, Ambrose T, Vento M, Carey LC, Cloutier CT: Effects of ibuprofen on a porcine model of acute respiratory failure. J Surg Res. 1984, 36 (4): 300-5.CrossRefPubMed Kopolovic R, Thrailkill KM, Martin DT, Ambrose T, Vento M, Carey LC, Cloutier CT: Effects of ibuprofen on a porcine model of acute respiratory failure. J Surg Res. 1984, 36 (4): 300-5.CrossRefPubMed
14.
go back to reference Balk RA, Jacobs RF, Tryka F, Townsed JW, Walls RC, Bone RC: Effects of ibuprofen on neutrophil function and acute lung injury in canine endotoxic shock. Crit Care Med. 1988, 16 (11): 1121-7.CrossRefPubMed Balk RA, Jacobs RF, Tryka F, Townsed JW, Walls RC, Bone RC: Effects of ibuprofen on neutrophil function and acute lung injury in canine endotoxic shock. Crit Care Med. 1988, 16 (11): 1121-7.CrossRefPubMed
15.
go back to reference Suffredini AF, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA, Parillo JE: The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med. 1989, 321 (5): 280-7.CrossRefPubMed Suffredini AF, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA, Parillo JE: The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med. 1989, 321 (5): 280-7.CrossRefPubMed
16.
go back to reference Bernard GR, Reines HD, Halushka PV, et al: Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome. Effects of cyclooxygenase inhibition. Am Rev Respir Dis. 1991, 144 (5): 1095-1101.CrossRefPubMed Bernard GR, Reines HD, Halushka PV, et al: Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome. Effects of cyclooxygenase inhibition. Am Rev Respir Dis. 1991, 144 (5): 1095-1101.CrossRefPubMed
17.
go back to reference Martich GD, Parker MM, Cunnion RE, Suffredini AF: Effects of ibuprofen and pentoxiphylline on the cardiovascular response of normal humans to endotoxin. J Appl Physiol. 1992, 73 (3): 925-31.PubMed Martich GD, Parker MM, Cunnion RE, Suffredini AF: Effects of ibuprofen and pentoxiphylline on the cardiovascular response of normal humans to endotoxin. J Appl Physiol. 1992, 73 (3): 925-31.PubMed
18.
go back to reference Revhaug A, Michie HR, Manson JM, Watters JM, Dinarello CA, Wolf SM, Willmore DW: Inhibition of cyclo-oxygenase attenuates the metabolic response to the endotoxin in humans. Arch Surg. 1988, 123 (2): 162-170.CrossRefPubMed Revhaug A, Michie HR, Manson JM, Watters JM, Dinarello CA, Wolf SM, Willmore DW: Inhibition of cyclo-oxygenase attenuates the metabolic response to the endotoxin in humans. Arch Surg. 1988, 123 (2): 162-170.CrossRefPubMed
19.
go back to reference Yamanaka S, Iwao H, Yukimura T, Kim S, Miura K: Effect of the thrombocyte-activating factor antagonist, TCV-309, and the cyclo-oxygenase inhibitor, ibuprofen, on the hemodynamic changes in canine experimental endotoxic shock. Br J Pharmacol. 1993, 110 (4): 1501-7.CrossRefPubMedPubMedCentral Yamanaka S, Iwao H, Yukimura T, Kim S, Miura K: Effect of the thrombocyte-activating factor antagonist, TCV-309, and the cyclo-oxygenase inhibitor, ibuprofen, on the hemodynamic changes in canine experimental endotoxic shock. Br J Pharmacol. 1993, 110 (4): 1501-7.CrossRefPubMedPubMedCentral
20.
go back to reference Beck RR, Abel FL: Effect of ibuprofen on the course of canine endotoxin shock. Circ Shock. 1987, 23 (1): 59-70.PubMed Beck RR, Abel FL: Effect of ibuprofen on the course of canine endotoxin shock. Circ Shock. 1987, 23 (1): 59-70.PubMed
21.
go back to reference Ebong S, Call D, Nemzek J, Bolgos G, Newcomb D, Remick D: Immunopathologic alterations in murine models of sepsis of increasing severity. Infection and Immunity. 1999, 66 (12): 6603-10. Ebong S, Call D, Nemzek J, Bolgos G, Newcomb D, Remick D: Immunopathologic alterations in murine models of sepsis of increasing severity. Infection and Immunity. 1999, 66 (12): 6603-10.
22.
go back to reference Haupt MT, Jastremski MS, Clemmer TP, Metz CA, Goris GB: Effect of ibuprofen in patients with severe sepsis: a randomized, double-blinded, multicenter study. The Ibuprofen Study Group. Crit Care Med. 1991, 19 (11): 1339-47.CrossRefPubMed Haupt MT, Jastremski MS, Clemmer TP, Metz CA, Goris GB: Effect of ibuprofen in patients with severe sepsis: a randomized, double-blinded, multicenter study. The Ibuprofen Study Group. Crit Care Med. 1991, 19 (11): 1339-47.CrossRefPubMed
23.
go back to reference Arons MM, Wheeler AP, Bernard GR, et al: Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. Crit Care Med. 1999, 27 (4): 699-707.CrossRefPubMed Arons MM, Wheeler AP, Bernard GR, et al: Effects of ibuprofen on the physiology and survival of hypothermic sepsis. Ibuprofen in Sepsis Study Group. Crit Care Med. 1999, 27 (4): 699-707.CrossRefPubMed
24.
go back to reference Mullen PG, Windsor AC, Walsh CJ, et al: Combined ibuprofen and monoclonal antibody to tumor necrosis factor-alpha attenuate hemodynamic dysfunction and sepsis-induced acute lung injury. J Trauma. 1993, 34 (5): 612-21.CrossRefPubMed Mullen PG, Windsor AC, Walsh CJ, et al: Combined ibuprofen and monoclonal antibody to tumor necrosis factor-alpha attenuate hemodynamic dysfunction and sepsis-induced acute lung injury. J Trauma. 1993, 34 (5): 612-21.CrossRefPubMed
25.
go back to reference Bjornson AB, Knippenberg RW, Bjornson HS: Nonsteroidal anti-inflammatory drugs correct the bactericidal defect of polymorphonuclear leukocytes in a guinea pig model of thermal injury. J Infect Dis. 1988, 157 (5): 959-67.CrossRefPubMed Bjornson AB, Knippenberg RW, Bjornson HS: Nonsteroidal anti-inflammatory drugs correct the bactericidal defect of polymorphonuclear leukocytes in a guinea pig model of thermal injury. J Infect Dis. 1988, 157 (5): 959-67.CrossRefPubMed
26.
go back to reference Baumgartner JD, Calandra T: Treatment of sepsis: Update on causes and complications. J Crit Ilness. 1999, 7: 1233-54. Baumgartner JD, Calandra T: Treatment of sepsis: Update on causes and complications. J Crit Ilness. 1999, 7: 1233-54.
27.
go back to reference Adams T, Traber DL: The effects of a prostaglandin synthetase inhibitor, ibuprofen, on the cardiopulmonary response to endotoxin in sheep. Circ Shock. 1982, 9 (5): 481-9.PubMed Adams T, Traber DL: The effects of a prostaglandin synthetase inhibitor, ibuprofen, on the cardiopulmonary response to endotoxin in sheep. Circ Shock. 1982, 9 (5): 481-9.PubMed
28.
go back to reference Fletcher JR, Collins JN, Graves ED, Luterman A, Williams MD, Izenberg SD: Tumor necrosis factor-induced mortality is reversed with cyclooxygenase inhibition. Ann Surg. 1993, 217 (6): 668-75.CrossRefPubMedPubMedCentral Fletcher JR, Collins JN, Graves ED, Luterman A, Williams MD, Izenberg SD: Tumor necrosis factor-induced mortality is reversed with cyclooxygenase inhibition. Ann Surg. 1993, 217 (6): 668-75.CrossRefPubMedPubMedCentral
29.
go back to reference Wise WC, Halushka PV, Knapp RG, Cook JA: Ibuprofen, methylprednisolone, and gentamicin as conjoint therapy in septic shock. Circ Shock. 1985, 17 (1): 59-71.PubMed Wise WC, Halushka PV, Knapp RG, Cook JA: Ibuprofen, methylprednisolone, and gentamicin as conjoint therapy in septic shock. Circ Shock. 1985, 17 (1): 59-71.PubMed
30.
go back to reference Rosello AM, Ferron-Orihuela JA, Ruiz-Cabello F, Garrote-Lara D, Fernandez-Mondeyar E, Delgado-Carrasco ML: Differential effects of IL-1β and ibuprofen after endotoxic challenge in mice. J Surg Research. 1997, 67 (2): 199-204. 10.1006/jsre.1996.4982.CrossRef Rosello AM, Ferron-Orihuela JA, Ruiz-Cabello F, Garrote-Lara D, Fernandez-Mondeyar E, Delgado-Carrasco ML: Differential effects of IL-1β and ibuprofen after endotoxic challenge in mice. J Surg Research. 1997, 67 (2): 199-204. 10.1006/jsre.1996.4982.CrossRef
31.
go back to reference Vural P, Canbaz M, Akbulut A, Celik I: Effects of ibuprofen on plasma endothelin levels and some vital parameters during endotoxin shock in rabbits. Clin Chim Acta. 2002, 316 (1–2): 101-8. 10.1016/S0009-8981(01)00740-9.CrossRefPubMed Vural P, Canbaz M, Akbulut A, Celik I: Effects of ibuprofen on plasma endothelin levels and some vital parameters during endotoxin shock in rabbits. Clin Chim Acta. 2002, 316 (1–2): 101-8. 10.1016/S0009-8981(01)00740-9.CrossRefPubMed
32.
go back to reference Schirmer WJ, Schirmer JM, Townsed MC, Fry DE: Effects of ibuprofen, indomethacin, and imidazole on survival in sepsis. Curr Surg. 1987, 44 (2): 102-5.PubMed Schirmer WJ, Schirmer JM, Townsed MC, Fry DE: Effects of ibuprofen, indomethacin, and imidazole on survival in sepsis. Curr Surg. 1987, 44 (2): 102-5.PubMed
33.
go back to reference Young JS, Passmore JC: Haemodynamic and renal advantages of dual cyclooxygenase and leukotriene blockade during canine endotoxic shock. Circ Shock. 1990, 32 (3): 243-55.PubMed Young JS, Passmore JC: Haemodynamic and renal advantages of dual cyclooxygenase and leukotriene blockade during canine endotoxic shock. Circ Shock. 1990, 32 (3): 243-55.PubMed
Metadata
Title
Effects of Ibuprofen on the physiology and outcome of rabbit endotoxic shock
Authors
Ilhami Celik
Ayhan Akbulut
S Sirri Kilic
Ali Rahman
Pervin Vural
Mukaddes Canbaz
Suleyman Felek
Publication date
01-12-2002
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2002
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-2-26

Other articles of this Issue 1/2002

BMC Infectious Diseases 1/2002 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.