Thromboxane-blocked swine as an experimental model of severe intravascular inflammation and septic shock

Shock
G Jesmok, R Gundel

Abstract

The cardiopulmonary response elicited by intravenous bacteria or endotoxin is well characterized in swine and has two major components. The first represents the acute pulmonary and broncho-constrictive phase (0-2 h) and the second phase (3-8 h) represents increased microvascular permeability, hypotension, and enhanced leukocyte-endothelial adhesion. The pulmonary vasoconstriction and bronchoconstriction of phase 1 results in acute pulmonary hypertension and airway dysfunction, which may result in rapid mortality. Because this acute pulmonary response may not mimic the development of human septic shock, we sought to block this early phase and examine the role of tumor necrosis factor in the latter septic phase (3-8 h). Employing a thromboxane A2 (TXA2) receptor antagonist (BAY U 3405) in the presence of LD100 Escherichia coli challenge, we blocked the acute pulmonary hypertensive phase and prevented early mortality, however, TXA2 blockade did not affect the latter development of septic shock and death. This latter lethal phase, characterized by prolonged leukopenia, was blocked in a dose-dependent manner by tumor necrosis factor monoclonal antibody. We conclude that the TXA2-blocked E. coli-challenged swine may provide a novel a...Continue Reading

Citations

Jul 1, 1997·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·B SchröppelU B Brückner
Feb 20, 2004·Archives of Physiology and Biochemistry·B LambermontV D'Orio
May 25, 2002·Artificial Cells, Blood Substitutes, and Immobilization Biotechnology·Erin FreilichJames Hebert

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