POTENTIAL ETIOLOGIC ROLE OF PAF IN 2 MAJOR SEPTIC COMPLICATIONS - DISSEMINATED INTRAVASCULAR COAGULATION AND MULTIPLE ORGAN FAILURE

A Possible role of platelet-activating factor (PAF) in the occurrence of the two septic complications, i.e., disseminated intravascular coag ulation (DIC) and multiple organ failure (MOF) was investigated, emplo ying a rabbit model and a novel PAF antagonist E5880. By an instillati on of fecal suspension into the common bile duct of the rabbit, manife stations of DIC and MOF were observed with high reproducibility by 9 h ours after the septic insult. E5880 was intravenously administered to 12 rabbits for 1 hour after the septic insult at dose of 1 mg/kg(n=6) or 3mg/kg(n=6). All the rabbits were subjected to observation of vital signs and serial determination of laboratory tests for 9 hours and th en lung, liver and kidney were removed for histological examination. B lood endotoxin level increased significantly by 9 hours after the sept ic insult. Although administration of E5880 did not affect the endotox emia, the antagonist attenuated in a dose related manner laboratory ma nifestation of DIC such as thrombocytopenia and prolonged prothrombin time as well as that of MOF such as increase in serum bibirubin and cr eatinine level. The beneficial effect of E5880 on MOF was also confirm ed by the histological evaluation. These observations indicated that P AF is deeply involved in the occurrence of DIC and MOF due to sepsis a nd E5880 may be one of the modalities to treat or prevent these two ma jor septic complications.