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William J. Schirmer, MD; James M. Schirmer; Donald E. Fry, MD

Arch Surg. 1989;124(4):445-448.

Abstract
• Tumor necrosis factor (TNF) is a macrophage-derived peptide mediator released during endotoxemia and sepsis. We examined the systemic and visceral hemodynamic response to low doses of human recombinant TNF in rats. Each animal received a 30-minute intravenous infusion of either saline solution (n=8) or TNF (n=8) in a dose of 0.25 mg/kg or 1.0 mg/kg. Thermodilution cardiac output, blood pressure, pulse, vascular resistance, effective hepatic blood flow (galactose clearance), and effective renal plasma flow (p-aminohippurate clearance) were determined at time=2 hours. The 0.25-mg/kg dose had no apparent effect on systemic hemodynamics. The 1.0-mg/kg dose produced a hyperdynamic systemic circulatory response with an elevated cardiac output, tachycardia, and a diminished systemic vascular resistance. Effective hepatic blood flow was exquisitely sensitive to even the lowest dose of TNF, with a 29% reduction despite the normal cardiac output. Renal flow was unaffected by either dose. Tumor necrosis factor–induced systemic and visceral hemodynamic changes are remarkably similar to those seen in gram-negative sepsis, suggesting that TNF may occupy a proximal position in the pathogenesis of overwhelming infection.

(Arch Surg 1989;124:445-448)

Author Affiliations
From the Departments of Surgery, Veterans Administration Medical Center and Case Western Reserve University Hospitals, Cleveland. Dr W. J. Schirmer is a Dudley P. Allen Fellow in surgical research of Case Western Reserve University Hospitals. Dr Fry is now with the Department of Surgery, University of New Mexico, Albuquerque.

Footnotes
Accepted for publication Oct 6, 1988.

Read before the 12th Annual Surgical Symposium of the Association of Veterans Administration Surgeons, Minneapolis, May 12, 1988.

Reprint requests to Department of Surgery 112W, Veterans Administration Medical Center, 10701 East Blvd, Cleveland, OH 44106 (Dr W. J. Schirmer).

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