ROLE OF PLATELET-ACTIVATING-FACTOR ANTAGONISM IN POSTHEMORRHAGE SEPTIC SHOCK IN PIGS

Objectives: To study the role of platelet-activating factor (PAF) anta gonism in posthemorrhage septic shock in pigs. Design: Experimental st udy. Materials and Methods: Twelve anesthetized pigs were bled, kept w ith a mean arterial pressure of 30 mm Hg for 30 minutes, and then resu scitated with 50 mL/kg of isotonic saline. A continuous infusion of Es cherichia coli endotoxin 36 mu g/kg/hour was give intravenously for 3. 5 hours starting 30 minutes after resuscitation. The animals were divi ded 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 resuscit ation, followed by a continuous infusion of BB-882 1 mg/kg/hour. The o ther group received vehicle alone. Measurements and Main Results: The measured variables were blood temperature, heart rate, intravascular p ressures, cardiac output, systemic and pulmonary vascular resistance, lung-thorax compliance, blood gases, hemoglobin oxygen saturation, pac ked cell volume, and blood sugar and serum lactic acid concentrations. The group treated with BB-882 had significantly higher intracardiac p ressures and cardiac output, and had less increase in systemic vascula r 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-induc ed hypoxia or reduced lung-thorax compliance. Conclusions: PAF antagon ism reduced the increase in systemic vascular resistance, improved car diac output, and reduced lactic acidemia in posthemorrhage septic shoc k in pigs, but it did not improve hypoxia or reduced lung-thorax compl iance.