Démolis P, Florence G, Thomas L, Tran Dinh Y R, Giudicelli J F, Seylaz J, Alkayed N J
Service de Pharmacologie Clinique, Hôpital de Bicêtre, Le Kremlin Bicetre, France.
Stroke. 2000 Feb;31(2):508-15. doi: 10.1161/01.str.31.2.508.
The cerebral vasodilating effect of acetazolamide (ACZ) injection has been used as an index of the autoregulatory vasodilation (or cerebral perfusion reserve). The question of whether the ACZ test assesses the maximal autoregulatory vasodilating capacity is not definitely resolved. The effects of ACZ injection on this reserve at a dose producing maximal vasodilation have never been evaluated and may help to resolve this problem.
The effect of ACZ injection on cerebral blood flow (CBF) autoregulation was tested in anesthetized rats. A pilot experiment evaluated the dose-effect relationship of injected ACZ, cumulative doses (n=4, group 1), and independent bolus doses (n=6, group 2). CBF was estimated by laser-Doppler flowmetry, and cerebrovascular resistance (CVR) was calculated from mean arterial blood pressure (MABP) and from CBF (expressed as a percentage of baseline CBF). A bolus of ACZ of 21 mg/kg produced the maximal cerebral vasodilation that could be obtained by ACZ administration. In the main experiment, MABP was lowered from 110 to 20 mm Hg by stepwise bleeding in 3 groups of 6 animals treated 10 minutes before bleeding by injection of saline (group 3), 7 mg/kg ACZ (group 4), or 21 mg/kg ACZ (group 5).
The CVR-MABP relationship was linear in all groups, indicating that CBF autoregulation was still effective after ACZ administration.
These results indicate that maximal ACZ-induced cerebral vasodilation is not quantitatively equivalent to maximal autoregulatory vasodilating capacity in anesthetized rats.
乙酰唑胺(ACZ)注射的脑血管舒张作用已被用作自动调节性血管舒张(或脑灌注储备)的指标。ACZ试验是否评估了最大自动调节性血管舒张能力的问题尚未明确解决。ACZ注射在产生最大血管舒张剂量时对该储备的影响从未被评估过,这可能有助于解决这个问题。
在麻醉大鼠中测试ACZ注射对脑血流量(CBF)自动调节的影响。一项预实验评估了注射ACZ的剂量-效应关系,累积剂量(n = 4,第1组)和独立推注剂量(n = 6,第2组)。通过激光多普勒血流仪估计CBF,并根据平均动脉血压(MABP)和CBF(表示为基线CBF的百分比)计算脑血管阻力(CVR)。21 mg/kg的ACZ推注产生了通过ACZ给药可获得的最大脑血管舒张。在主要实验中,通过逐步放血将MABP从110降至20 mmHg,在放血前10分钟,3组每组6只动物分别注射生理盐水(第3组)、7 mg/kg ACZ(第4组)或21 mg/kg ACZ(第5组)进行处理。
所有组中CVR-MABP关系均呈线性,表明ACZ给药后CBF自动调节仍然有效。
这些结果表明,在麻醉大鼠中,最大ACZ诱导的脑血管舒张在数量上不等同于最大自动调节性血管舒张能力。