Role of platelet-activating factor antagonism in posthemorrhage septic shock in pigs

Objectives: To study the role of platelet-activating factor (PAF) antagonism in posthemorrhage septic shock in pigs. Design: Experimental study. Materials and Methods: Twelve anesthetized pigs were bled, kept with a mean arterial pressure of 30 mm Hg for 30 minutes, and then resuscitated with 50 mL/kg of isotonic saline. A continuous infusion of Escherichia coli endotoxin 36 mu g/kg/hour was give intravenously for 3.5 hours starting 30 minutes after resuscitation. The animals were divided into two groups of six each. One group received 1 mg/kg of BB-882 (a potent specific PAF receptor antagonist) as a bolus during resuscitation, followed by a continuous infusion of BB-882 1 mg/kg/hour. The other group received vehicle alone. Measurements and Main Results: The measured variables were blood temperature, heart rate, intravascular pressures, cardiac output, systemic and pulmonary vascular resistance, lung-thorax compliance, blood gases, hemoglobin oxygen saturation, packed cell volume, and blood sugar and serum lactic acid concentrations. The group treated with BB-882 had significantly higher intracardiac pressures and cardiac output, and had less increase in systemic vascular resistance. The BB-882 group had significantly less lactic acidemia than the control group (p < 0.05, analysis of variance appropriate for repeated measurement design). BB-882 had no effect on endotoxin-induced hypoxia or reduced lung-thorax compliance. Conclusions: PAF antagonism reduced the increase in systemic vascular resistance, improved cardiac output, and reduced lactic acidemia in posthemorrhage septic shock in pigs, but it did not improve hypoxia or reduced lung-thorax compliance.