Javaheri S, Corbett W S, Simbartl L A, Mehta S, Khosla A
VA Medical Center, Department of Medicine, University of Cincinnati College of Medicine, OH 45220, USA.
Brain Res. 1997 Apr 18;754(1-2):321-4. doi: 10.1016/s0006-8993(97)00175-3.
We investigated the effects of omeprazole and Sch 28080, a more specific and a more potent inhibitor of K+,H+-ATPase than omeprazole, in canine cerebrospinal fluid (CSF) production. CSF production was measured by ventriculocisternal perfusion (VCP) technique in three groups (n = 10 in each group) of anesthetized, paralyzed and mechanically ventilated dogs. Group I served as control, Sch 28080 (10(-4) mol/l of synthetic CSF) was added to VCP in group II, and omeprazole (10(-5) mol/l of synthetic CSF) was added to VCP in group III, after baseline control CSF production had been determined at 15, 30, 45, and 60 min. Comparing the three groups, the mean baseline values for CSF production did not differ significantly. However, the percent decreases in CSF production in the omeprazole treated group were 26 +/- 17 and 24 +/- 13 at 210 and 225 min, which were significantly more than the respective values in the control group. Percent decrease in CSF production in Sch 28080 was not significantly different from that in the control group. We conclude that in the canine model, physiological doses of omeprazole decrease CSF production by about 26%. However, the effect is independent of the K+,H+-ATPase activity, since Sch 28080 which is more potent than omeprazole did not significantly affect CSF production.
我们研究了奥美拉唑以及Sch 28080(一种比奥美拉唑更具特异性、更强效的钾离子/氢离子-ATP酶抑制剂)对犬脑脊液(CSF)生成的影响。通过脑室池灌注(VCP)技术,在三组(每组n = 10只)麻醉、麻痹并机械通气的犬中测量CSF生成量。在15、30、45和60分钟测定基线对照CSF生成量后,第一组作为对照,第二组在VCP中加入Sch 28080(10⁻⁴mol/l合成脑脊液),第三组在VCP中加入奥美拉唑(10⁻⁵mol/l合成脑脊液)。比较三组,CSF生成的平均基线值无显著差异。然而,奥美拉唑治疗组在210和225分钟时CSF生成量的减少百分比分别为26±17和24±13,显著高于对照组的相应值。Sch 28080组CSF生成量的减少百分比与对照组无显著差异。我们得出结论,在犬模型中,生理剂量的奥美拉唑可使CSF生成量减少约26%。然而,该作用与钾离子/氢离子-ATP酶活性无关,因为比奥美拉唑更强效的Sch 28080并未显著影响CSF生成。