Effects of ONO-6240, a platelet-activating factor antagonist, on endotoxin shock in unanesthetized sheep.
To determine the role of platelet-activating factor (PAF) in endotoxin shock, we studied the effects of ONO-6240, a PAF antagonist, on endotoxin shock in unanesthetized sheep. Changes in hemodynamics, lung lymph balance, leukocyte and platelet counts, and arterial blood gas tensions were measured in four groups; endotoxin alone; endotoxin plus ONO-6240; ONO-6240 alone; vehicle control. Pretreatment with ONO-6240 in sheep given endotoxin significantly prevented the decreases in systemic arterial pressure, left atrial pressure and cardiac output observed in sheep given endotoxin alone. A partial effect on diminishing the magnitude of peripheral leukopenia was also noted. However, pretreatment with ONO-6240 had little effect on pulmonary hypertension and lung lymph balance. We conclude that endotoxin causes two different effects: vascular collapse and direct lung injury; and that PAF is involved only in the circulatory manifestations.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004731:Endotoxins; D006439:Hemodynamics / Q000187:drug effects*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects; D008196:Lymph / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000097:blood*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000494:pharmacology; D010976:Platelet Count; D012756:Sheep; D012772:Shock, Septic / Q000503:physiopathology*; D013844:Thiazoles; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D010972:Platelet Activating Factor; D013844:Thiazoles; C048549:ONO 6240; D010100:Oxygen