Effects of ONO-6240, a platelet-activating factor antagonist, on endotoxin shock in unanesthetized sheep.

Abstract

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.

• Authors: T Toyofuku, K Kubo, T Kobayashi, S Kusama
• Journal: Prostaglandins (Prostaglandins) Vol. 31 Issue 2 Pg. 271-81 (Feb 1986) ISSN: 0090-6980 [Print] United States
• PMID: 3754344 (Publication Type: Journal Article)

Chemical References

• Endotoxins
• Platelet Activating Factor
• Thiazoles
• ONO 6240
• Oxygen

Topics

• Animals
• Blood Pressure (drug effects)
• Cardiac Output (drug effects)
• Endotoxins
• Hemodynamics (drug effects)
• Leukocyte Count
• Lung (drug effects)
• Lymph (drug effects, physiology)
• Oxygen (blood)
• Platelet Activating Factor (analogs & derivatives, pharmacology)
• Platelet Count
• Sheep
• Shock, Septic (physiopathology)
• Thiazoles
• Vascular Resistance (drug effects)