THROMBOXANE-BLOCKED SWINE AS AN EXPERIMENTAL-MODEL OF SEVERE INTRAVASCULAR INFLAMMATION AND SEPTIC SHOCK

The cardiopulmonary response elicited by intravenous bacteria or endot oxin is well characterized in swine and has two major components. The first represents the acute pulmonary and bronchoconstrictive phase (0- 2 h) and the second phase (3-8 h) represents increased microvascular p ermeability, hypotension, and enhanced leukocyte-endothelial adhesion. The pulmonary vasoconstriction and bronchoconstriction of phase 1 res ults 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 th is early phase and examine the role of tumor necrosis factor in the la tter septic phase (3-8 h). Employing a thromboxane A(2) (TXA(2)) recep tor antagonist (BAY U 3405) in the presence of LD(100) Escherichia coi l challenge, we blocked the acute pulmonary hypertensive phase and pre vented early mortality, however, TXA(2) blockade did not affect the la tter 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 TXA(2)-blocked E. coli-challenged swine may provide a novel anima l model in which to investigate the pathophysiology of acute septic sh ock.