Sensitivity to endotoxin in rabbits is increased after hemorrhagic shock

The immunoinflammatory response following trauma and hemorrhage may predispose to the development of sepsis and multiple-organ failure syndrome. Cardiac output (CO), arterial pressure, arterial PO₂, and pulmonary permeability index were measured. We examined the sensitivity of rabbits to infusions of lipopolysaccharide (LPS) after hemorrhagic shock. Shock was produced by reducing CO to 40% of baseline for 90 min, followed by resuscitation with shed blood and then with lactated Ringer solution to maintain CO near baseline. Animals were assigned to three groups: 1) hemorrhagic shock only, 2) LPS only, and 3) hemorrhagic shock + LPS. Groups 1 and 3 were subjected to hemorrhagic shock on day 1. Escherichia coli LPS was infused (1.0 μg/kg iv) into groups 2 and 3 on day 2. Fluid resuscitation with lactated Ringer solution was continued in an effort to maintain CO at baseline. Five hours after LPS infusion, ¹²⁵I-albumin was injected intravenously, and rabbits were killed 1 h later for measurement of pulmonary permeability index. LPS infusion after shock (group 3) caused significant decreases in CO, arterial pressure, and PO₂ and an increase in pulmonary permeability. These changes were not seen in the groups 1 and 2. We conclude that hemorrhagic shock and resuscitation result in a proinflammatory state, leading to increased sensitivity to subsequent exposure to LPS.