Tnf[alpha] and the pathophysiology of endotoxin-induced acute respiratory failure in sheep. Perkowski, Sandra Z., Peter J. Sloane, James A. Spath, Jr, Ted H. Elsasser, Jill K. Fisher, and Marlys H. Gee. Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania and Department of Physiology and Department of Medicine, Division of Pulmonary Medicine and Critical Care, Jefferson Medical College, Thomas Jefferson University and USDA Ruminant Laboratory, Beltsville, MD
APStracts 2:0447A, 1995.
We studied changes in cardiovascular and pulmonary function during prolonged endotoxemia in conscious sheep. Sheep with chronic lung lymph fistulas received a 12 hour infusion of E. coli endotoxin (10 ng/kg.min) followed by a 12 hour recovery period. Supportive therapies were withheld. Prolonged endotoxemia without volume support caused systemic hypotension associated with reduced cardiac output and increased systemic vascular resistance, pulmonary hypertension, and acute lung injury with progressive respiratory failure. Plasma TNF[alpha] concentrations increased transiently. Sustained pulmonary hypertension and increased pulmonary and systemic vascular resistances contributed to poor outcome in 9 of 34 sheep (26%). Plasma TNF[alpha] concentrations were significantly greater in survivors with sustained pulmonary hypertension and in nonsurviving sheep than in surviving sheep without pulmonary hypertension. Endotoxin (1 ng/ml) increased neutrophil expression of TNF[alpha] in vitro. Addition of interleukin-6 prevented this response. Synthesis and release of TNF[alpha] may be an important proximal event influencing the development of sustained pulmonary hypertension and progressive respiratory failure with endotoxemia. Interleukin-6 may contribute to the phasic nature of the TNF[alpha] response. 

Received 7 April 1995; accepted in final form 5 September 1995.
APS Manuscript Number A378-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95