TREATMENT WITH A PLATELET-ACTIVATING-FACTOR ANTAGONIST HAS LITTLE PROTECTIVE EFFECTS DURING ENDOTOXIC-SHOCK IN THE DOG

Platelet-activating factor (PAF) is a potent vasoactive and inflammato ry lipid mediator which has been implicated in the hemodynamic alterat ions of endotoxemia and sepsis. Different PAF receptor antagonists hav e been shown to attenuate the systemic and pulmonary disturbances of s epsls, but they were generally administered before the injection of en dotoxin and their effects have not been consistent, To examine the eff ects of BB-882, a novel potent PAF receptor antagonist, on general hem odynamics and regional flow distribution in a canine endotoxic shock m odel, 14 anesthetized and ventilated dogs received 2 mg/kg of Escheric hia coil endotoxin intravenously (i.v.) followed by generous fluid res uscitation. Thirty minutes later, the dogs received either BB-882 (n = 7) as a continuous i.v. infusion with hourly increasing doses (2, 5, and 10 mg/kg.h, respectively) or a corresponding amount of saline (n = 7). The administration of BB-882 resulted in a dose-dependent reducti on in cardiac output and an increase in systemic and pulmonary vascula r resistance. Mesenteric and renal flow were not different from contro l values whereas femoral blood flow progressively decreased. Another g roup of 7 dogs received 5 mg/kg i.v. bolus of BB-882 30 min before end otoxin. Pretreatment significantly increased mesenteric blood flow by about 50% but did not show any significant hemodynamic effects. This s tudy demonstrates that the administration of a PAF receptor antagonist following endotoxic shock in fluid resuscitated dogs does not offer s ignificant hemodynamic benefit. Pretreatment with BB-882 at the dose u sed only enhanced mesenteric perfusion. These findings do not support beneficial effects of PAF receptor antagonists in septic shock.