Inhibition of tumor necrosis factor prevents myocardial dysfunction during burn shock.
Tumor necrosis factor-alpha (TNF) is a pluripotent cytokine that mediates many of the hemodynamic manifestations of endotoxic shock. To determine whether TNF is responsible for postburn myocardial dysfunction, we compared cardiac function (Langendorff preparation) in 49 guinea pigs 18 h after thermal injury. Group 1 (n = 15) was sham burned; all remaining animals received a 43% surface area burn under anesthesia. Group 2 (n = 15) received lactated Ringer solution (LR, 4 ml.kg-1.%burn-1). Group 3 (n = 9) received LR and drug vehicle. Group 4 (n = 10) received LR plus 1 mg of TNF inhibitor consisting of the human p80 TNF receptor linked to the Fc portion of human immunoglobulin G1, which was shown to specifically bind and neutralize TNF secreted by guinea pig peritoneal macrophages in vitro. Burn injury caused a significant fall in left ventricular pressure (LVP, from 86 +/- 2 to 62 +/- 3 mmHg, P < 0.05) and maximal rate of LVP rise (+) and fall (-) (+/- dP/dtmax) [from 1,365 +/- 42 to 1,109 +/- 44 mmHg/s (P < 0.05) and from 1,184 +/- 31 to 881 +/- 40 mmHg/s (P < 0.05), respectively], a decrease in time to peak systolic LVP (from 111 +/- 2 to 102 +/- 2 ms, P < 0.05), and a decrease in time to +dP/dtmax (from 57 +/- 1 to 48 +/- 1 ms, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Giroir
B P
BP
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9031.
Horton
J W
JW
White
D J
DJ
McIntyre
K L
KL
Lin
C Q
CQ
D000818:Animals; D002056:Burns / Q000503:physiopathology*; D002319:Cardiovascular System / Q000503:physiopathology; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012774:Shock, Traumatic / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D011961:Receptors, Fc; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha