Winslow C, Dorinsky P M
Department of Medicine, Ohio State University, Columbus 43210.
J Crit Care. 1994 Sep;9(3):159-68. doi: 10.1016/0883-9441(94)90012-4.
The aim of this study was to determine whether the improved hemodynamic profiles reported with cyclooxygenase inhibition during sepsis include improvements in tissue perfusion is unknown. Our hypothesis was that cyclooxygenase inhibition with ibuprofen will prevent the endotoxin-induced alterations in regional blood flow distribution from developing and/or restore the endotoxin-induced loss of responsiveness to intravascular volume expansion.
We measured cardiac output, regional blood flow, and total systemic shunt flow in dogs using radiolabeled 15-microns microspheres. These parameters were assessed in control (N = 10) and endotoxin-treated animals (N = 7). Additional endotoxin-treated animals (N = 7) were also pretreated with ibuprofen.
Compared with controls, endotoxin-treated animals exhibited marked reductions in blood flow to most systemic organs that were not reversed with large, intravenous saline infusions (ie, isotonic saline; 40 mL/kg; N = 4). By contrast, although ibuprofen pretreatment (12.5 mg/kg; N = 7) completely prevented the reductions in mean arterial pressure caused by endotoxin from occurring, it did little to prevent the development of endotoxin-induced alterations in regional blood flow distribution. Nonetheless, in contrast to the endotoxin-treated animals, there were significant increases in cardiac output and blood flow to several organs after saline infusion in the ibuprofen-pretreated animals.
Cyclooxygenase inhibition with ibuprofen has few direct effects on regional blood flow distribution after endotoxin. However, cyclooxygenase inhibition with ibuprofen does attenuate the endotoxin-induced decrease in vascular responsiveness to intravenous saline infusion.
本研究旨在确定脓毒症期间环氧化酶抑制所报告的改善的血流动力学状况是否包括组织灌注的改善，目前尚不清楚。我们的假设是，布洛芬抑制环氧化酶将预防内毒素诱导的局部血流分布改变的发生和/或恢复内毒素诱导的对血管内容量扩张反应性的丧失。
我们使用放射性标记的15微米微球测量犬的心输出量、局部血流量和全身总分流流量。在对照动物（n = 10）和内毒素处理的动物（n = 7）中评估这些参数。另外的内毒素处理动物（n = 7）也用布洛芬进行预处理。
与对照相比，内毒素处理的动物表现出大多数全身器官血流量显著减少，大剂量静脉输注生理盐水（即等渗盐水；40 mL/kg；n = 4）不能逆转这种减少。相比之下，尽管布洛芬预处理（12.5 mg/kg；n = 7）完全预防了内毒素引起的平均动脉压降低的发生，但它对内毒素诱导的局部血流分布改变的发展几乎没有预防作用。尽管如此，与内毒素处理的动物不同，在布洛芬预处理的动物中静脉输注生理盐水后心输出量和几个器官的血流量有显著增加。
布洛芬抑制环氧化酶对内毒素后的局部血流分布几乎没有直接影响。然而，布洛芬抑制环氧化酶确实减弱了内毒素诱导的血管对静脉输注生理盐水反应性的降低。
