Effect of Ibuprofen on interleukin-1beta-induced abnormalities in hemodynamics and oxygen metabolism in rabbits.

We showed previously that the administration of interleukin (IL)-1beta induces circulatory shock and impairs the oxygen consumption (VO2)/oxygen delivery (DO2) relation by increasing the slope of the supply-independent line in rabbits. We tested the effect of ibuprofen, a specific inhibitor of the development of shock in this model, on the VO2/DO2 abnormality. Eighteen rabbits were divided randomly into three groups (n = 6 each) and intravenously given 10 microg/kg of IL-1beta alone or 10 microg/kg of IL-1beta followed by 10 mg/kg of ibuprofen or saline (control). All rabbits were subjected to stepwise cardiac tamponade by inflation of a handmade balloon placed into the pericardial sac to reduce DO2. The VO2/DO2 relation was then analyzed by the dual line method. The IL-1beta group had a significantly lower mean arterial pressure than that of the other groups before cardiac tamponade, and this reduction in mean arterial pressure was suppressed completely by treatment with ibuprofen. The cardiac index did not differ between groups. The slope of the supply-independent line was increased significantly by administration of IL-1beta, and this increase was attenuated significantly by treatment with ibuprofen (IL-1beta only: y = 0.14x + 6.1, ibuprofen: y = 0.06x + 8.5, control: y = 0.01x + 9.0). We conclude that ibuprofen reversed the IL-1beta-induced shock by restoring the systemic vascular resistance to normal and thereby normalized the VO2/DO2 relation in the supply-independent range of DO2.