TY - JOUR
T1 - The effects of tumor necrosis factor and their selective inhibition by ibuprofen
AU - Evans, D. A.
AU - Jacobs, D. O.
AU - Revhaug, A.
AU - Wilmore, D. W.
PY - 1989
Y1 - 1989
N2 - High doses of tumor necrosis factor (TNF) cause hypotension, metabolic acidosis and, death. At Brigham and Women's Hospital, the effects of a sublethal, 6-hour infusion of TNF (0.57 x 105 Units/kg body weight) in twelve anesthetized dogs were studied. This dose caused falls in mean arterial pressure from 153 mmHg to 96 mmHg, pulmonary artery pressure (-4.5 mmHg), central venous pressure (-2.5 mmHg) and pulmonary capillary wedge pressures (-5.25 mmHg). Associated with these responses were a fourfold increase in urine volume (22.4 ml/kg/6 hours as compared to 5.2 ml/kg/6 hours in controls), significant pyrexia (from 38.1 C to 39.5 C, rectal), tachycardia (from 125 to 175 beats/minute), and hypermetabolism. In addition, leukopenia and increased circulating stress hormone concentrations were observed. Blood glucose concentrations fell from 4.68 mM/l to 3.97 mM/l (84-71 mg/dl) within 3 hours of TNF infusion, whereas lactate and pyruvate concentrations increased. These alterations occurred in the absence of severe hypotension or acidosis and were similar to changes observed after endotoxin administration or gram-negative septicemia. Pretreatment of the animals with the cyclooxygenase inhibitor ibuprofen abolished most of the hemodynamic changes and attenuated other responses. These findings support the hypothesis that TNF is an important mediator of septic responses and that some of the effects of TNF are mediated via cyclooxygenase pathways.
AB - High doses of tumor necrosis factor (TNF) cause hypotension, metabolic acidosis and, death. At Brigham and Women's Hospital, the effects of a sublethal, 6-hour infusion of TNF (0.57 x 105 Units/kg body weight) in twelve anesthetized dogs were studied. This dose caused falls in mean arterial pressure from 153 mmHg to 96 mmHg, pulmonary artery pressure (-4.5 mmHg), central venous pressure (-2.5 mmHg) and pulmonary capillary wedge pressures (-5.25 mmHg). Associated with these responses were a fourfold increase in urine volume (22.4 ml/kg/6 hours as compared to 5.2 ml/kg/6 hours in controls), significant pyrexia (from 38.1 C to 39.5 C, rectal), tachycardia (from 125 to 175 beats/minute), and hypermetabolism. In addition, leukopenia and increased circulating stress hormone concentrations were observed. Blood glucose concentrations fell from 4.68 mM/l to 3.97 mM/l (84-71 mg/dl) within 3 hours of TNF infusion, whereas lactate and pyruvate concentrations increased. These alterations occurred in the absence of severe hypotension or acidosis and were similar to changes observed after endotoxin administration or gram-negative septicemia. Pretreatment of the animals with the cyclooxygenase inhibitor ibuprofen abolished most of the hemodynamic changes and attenuated other responses. These findings support the hypothesis that TNF is an important mediator of septic responses and that some of the effects of TNF are mediated via cyclooxygenase pathways.
UR - http://www.scopus.com/inward/record.url?scp=0024562975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024562975&partnerID=8YFLogxK
U2 - 10.1097/00000658-198903000-00011
DO - 10.1097/00000658-198903000-00011
M3 - Article
C2 - 2538107
AN - SCOPUS:0024562975
SN - 0003-4932
VL - 209
SP - 312
EP - 321
JO - Annals of surgery
JF - Annals of surgery
IS - 3
ER -