Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet: Influence of cyclooxygenase inhibition

H. Osiovich, R. N. Goldberg, C. Sugihara, J. A. Adams, Octavio V. Martinez, G. Kuo, William J Feuer, S. Offenbacher, Eduardo Bancalari

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Abstract

Tumor necrosis factor-α (TNF) is believed to play an important role in mediating many of the pathophysiologic changes accompanying bacterial sepsis. In order to characterize the cardiopulmonary responses to TNF in a young animal model and to determine to what extent these changes were secondary to cyclooxygenase byproducts, three groups of mechanically ventilated piglets received an infusion of either TNF, indomethacin followed by TNF (Indo + TNF) or neither (control). Compared to controls at 120 min, TNF resulted in the following changes beginning 30-60 min after the infusion began: mean pulmonary artery pressure (P̄(pa)) increased from 1.7 ± 0.3 to 4.4 ± 0.7 kPa (13 ± 2 to 33 ± 5 mm Hg) (p < 0.001); cardiac output (CO) fell from 0.28 ± 0.05 to 0.20 ± 0.07 liters/kg/min (p < 0.01); mean arterial blood pressure (P̄(sa)) decreased from 9.5 ± 1.2 to 7.9 ± 1.9 kPa (71 ± 9 to 59 ± 14 mm Hg) as did pH from 7.49 ± 0.04 to 7.13 ± 0.17 (p < 0.001). Dynamic lung compliance (C(dyn)) also decreased; however, pulmonary resistance (R(I)) remained unchanged. Thromboxane B2 (TxB2) rose in all animals at 60 min coincident with P̄(sa) elevation and was significantly blocked by Indo (p < 0.03). In the Indo + TNF group the early TNF-induced rise in P̄(sa) was blunted compared to the TNF group [2.9 ± 1.2 vs. 3.6 ± 0.8 kPa (22 ± 3 vs. 27 ± 6 mm Hg; p < 0.04)] as were the late decreases in pH and P̄(sa) (p < 0.04). There were no significant changes in C(dyn) secondary to Indo. Although delayed, the hemodynamic changes observed with TNF infusion are similar to those reported for piglets receiving group B streptococci; however, in contrast to the latter the early changes secondary to TNF are only mildly effected by indomethacin. The significant improvement in the late occurring hypotension and acidosis suggests that TNF may act in part via the cyclooxygenase pathway as a mediator of the late hypotension associated with sepsis.

Original languageEnglish
Pages (from-to)342-353
Number of pages12
JournalBiology of the Neonate
Volume68
Issue number5
StatePublished - Dec 1 1995

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Prostaglandin-Endoperoxide Synthases
Tumor Necrosis Factor-alpha
Indomethacin
Hypotension
Sepsis
Arterial Pressure
Lung Compliance
Thromboxane B2
Streptococcus agalactiae
Acidosis
Cardiac Output
Pulmonary Artery
Animal Models
Hemodynamics
Pressure

Keywords

  • Cyclooxygenase byproducts
  • Indomethacin
  • Piglets
  • Pulmonary function
  • Sepsis
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health

Cite this

Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet : Influence of cyclooxygenase inhibition. / Osiovich, H.; Goldberg, R. N.; Sugihara, C.; Adams, J. A.; Martinez, Octavio V.; Kuo, G.; Feuer, William J; Offenbacher, S.; Bancalari, Eduardo.

In: Biology of the Neonate, Vol. 68, No. 5, 01.12.1995, p. 342-353.

Research output: Contribution to journalArticle

Osiovich, H, Goldberg, RN, Sugihara, C, Adams, JA, Martinez, OV, Kuo, G, Feuer, WJ, Offenbacher, S & Bancalari, E 1995, 'Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet: Influence of cyclooxygenase inhibition', Biology of the Neonate, vol. 68, no. 5, pp. 342-353.
Osiovich, H. ; Goldberg, R. N. ; Sugihara, C. ; Adams, J. A. ; Martinez, Octavio V. ; Kuo, G. ; Feuer, William J ; Offenbacher, S. ; Bancalari, Eduardo. / Cardiopulmonary effects of tumor necrosis factor-alpha in the piglet : Influence of cyclooxygenase inhibition. In: Biology of the Neonate. 1995 ; Vol. 68, No. 5. pp. 342-353.
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abstract = "Tumor necrosis factor-α (TNF) is believed to play an important role in mediating many of the pathophysiologic changes accompanying bacterial sepsis. In order to characterize the cardiopulmonary responses to TNF in a young animal model and to determine to what extent these changes were secondary to cyclooxygenase byproducts, three groups of mechanically ventilated piglets received an infusion of either TNF, indomethacin followed by TNF (Indo + TNF) or neither (control). Compared to controls at 120 min, TNF resulted in the following changes beginning 30-60 min after the infusion began: mean pulmonary artery pressure (P̄(pa)) increased from 1.7 ± 0.3 to 4.4 ± 0.7 kPa (13 ± 2 to 33 ± 5 mm Hg) (p < 0.001); cardiac output (CO) fell from 0.28 ± 0.05 to 0.20 ± 0.07 liters/kg/min (p < 0.01); mean arterial blood pressure (P̄(sa)) decreased from 9.5 ± 1.2 to 7.9 ± 1.9 kPa (71 ± 9 to 59 ± 14 mm Hg) as did pH from 7.49 ± 0.04 to 7.13 ± 0.17 (p < 0.001). Dynamic lung compliance (C(dyn)) also decreased; however, pulmonary resistance (R(I)) remained unchanged. Thromboxane B2 (TxB2) rose in all animals at 60 min coincident with P̄(sa) elevation and was significantly blocked by Indo (p < 0.03). In the Indo + TNF group the early TNF-induced rise in P̄(sa) was blunted compared to the TNF group [2.9 ± 1.2 vs. 3.6 ± 0.8 kPa (22 ± 3 vs. 27 ± 6 mm Hg; p < 0.04)] as were the late decreases in pH and P̄(sa) (p < 0.04). There were no significant changes in C(dyn) secondary to Indo. Although delayed, the hemodynamic changes observed with TNF infusion are similar to those reported for piglets receiving group B streptococci; however, in contrast to the latter the early changes secondary to TNF are only mildly effected by indomethacin. The significant improvement in the late occurring hypotension and acidosis suggests that TNF may act in part via the cyclooxygenase pathway as a mediator of the late hypotension associated with sepsis.",
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AU - Adams, J. A.

AU - Martinez, Octavio V.

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