Harkin C P, Hudetz A G, Schmeling W T, Kampine J P, Farber N E
Department of Anesthesiology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee 53226, USA.
Anesthesiology. 1997 Apr;86(4):885-94. doi: 10.1097/00000542-199704000-00019.
Halothane is a potent dilator of cerebral arteries. The predominant site of cerebrovascular resistance is thought to be intracerebral arterioles, and the effects of halothane on these vessels were not previously examined. This study compared the effects of halothane with those of the vasodilator and nitric oxide donor, sodium nitroprusside, on intraparenchymal microvessel responsiveness in a brain slice preparation.
Anesthetized Sprague-Dawley rats underwent thoracotomy and intracardiac perfusion and then were decapitated. Hippocampal brain slices were prepared and placed in a perfusion/recording chamber and superfused with artificial cerebrospinal fluid. An arteriole was located within the brain parenchyma and its diameter was monitored with videomicroscopy before, during, and after various concentrations of halothane or sodium nitroprusside were equilibrated in the perfusate. All vessels were preconstricted with prostaglandin F2 alpha before halothane or sodium nitroprusside treatment. An observer blinded to treatment analyzed vessel diameter changes with a computerized videomicrometer.
Baseline microvessel diameter was 18 +/- 2 microns in the halothane group (n = 14) and 15 +/- 1 microns in the sodium nitroprusside group (n = 15). Prostaglandin F2 alpha (0.5 micron) preconstricted vessels by approximately 15% from resting diameter in both groups. Halothane significantly and dose dependently dilated intracerebral microvessels by 54% +/- 6%, 74% +/- 8%, 108% +/- 13%, and 132% +/- 7% (normalized to the preconstricted diameter) at 0.5%, 1.0%, and 2.5% halothane, respectively. This dilatation corresponds to a decrease in a calculated index of cerebrovascular resistance index of up to 117% +/- 2% at 2.5% halothane. Sodium nitroprusside, in concentrations ranging from 10(-8) to 10(-3)M, also dose dependently dilated these intraparenchymal vessels by 129% +/- 7% at the highest concentration. These alterations in microvessel diameter corresponded to a decrease in the cerebrovascular resistance index of up to 116 +/- 4% for the largest dose.
Halothane produces dose-dependent vasodilatation of intraparenchymal cerebral microvessels, thus predicting marked decreases in cerebrovascular resistance in this in vitro brain slice preparation. The effects of halothane on these cerebral microvessels are similar to those of the potent vasodilator sodium nitroprusside. These findings suggest that direct effects of halathane on cerebral microvessels diameter contribute substantially to alterations in cerebrovascular resistance and flow produced by this agent.
氟烷是一种强效的脑动脉扩张剂。脑血管阻力的主要部位被认为是脑内小动脉，而氟烷对这些血管的作用此前未被研究过。本研究比较了氟烷与血管扩张剂及一氧化氮供体硝普钠对脑片制备中脑实质微血管反应性的影响。
对麻醉的Sprague-Dawley大鼠进行开胸和心内灌注，然后断头。制备海马脑片并置于灌注/记录室，用人工脑脊液进行灌流。在灌注液中平衡不同浓度的氟烷或硝普钠之前、期间和之后，通过视频显微镜监测位于脑实质内的一条小动脉的直径。在氟烷或硝普钠处理前，所有血管均用前列腺素F2α预收缩。一位对处理不知情的观察者用计算机化视频测微仪分析血管直径变化。
氟烷组（n = 14）的基线微血管直径为18±2微米，硝普钠组（n = 15）为15±1微米。前列腺素F2α（0.5微米）使两组血管从静息直径预收缩约15%。氟烷在0.5%、1.0%和2.5%浓度时，分别使脑内微血管显著且剂量依赖性地扩张54%±6%、74%±8%、108%±13%和132%±7%（相对于预收缩直径）。在2.5%氟烷时，这种扩张相当于计算得出的脑血管阻力指数下降高达117%±2%。硝普钠浓度范围为10(-8)至10(-3)M时，在最高浓度下也使这些脑实质内血管剂量依赖性地扩张129%±7%。微血管直径的这些变化相当于最大剂量时脑血管阻力指数下降高达116±4%。
氟烷可使脑实质内脑微血管产生剂量依赖性血管扩张，从而预示在这种体外脑片制备中脑血管阻力会显著降低。氟烷对这些脑微血管的作用与强效血管扩张剂硝普钠相似。这些发现表明，氟烷对脑微血管直径的直接作用在很大程度上导致了该药物引起的脑血管阻力和血流的改变。
