Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street PH 5, New York, NY 10032, United States.
Neurosci Lett. 2010 Mar 8;471(3):166-70. doi: 10.1016/j.neulet.2010.01.034. Epub 2010 Jan 25.
The differential effects of age-adjusted equipotent doses of isoflurane (Iso) and desflurane (Des) on hippocampal acetylcholine (ACh) levels were examined using cerebral microdialysis in young (12-16 weeks old) and aged (16-18 months old) Fischer 344 rats. An 80min exposure to 1 minimum alveolar concentration (MAC) of isoflurane and desflurane produced similar maximal decreases in hippocampal ACh levels in both age groups: to 36.3+/-13.9% (Iso) and 28.6+/-12.9% (Des) of baseline in aged rats versus 32.5+/-18.7% (Iso) and 29.6+/-12.5% (Des) of baseline in young rats. Compared to isoflurane, the onset of this maximal decrease was delayed in both age groups with desflurane. Furthermore, following the end of anesthesia in aged rats, hippocampal ACh levels returned to control levels faster with desflurane (within 20-40min) than isoflurane (within 60-80min). These data demonstrate that age-adjusted equipotent doses of isoflurane and desflurane produce similar maximal decreases in hippocampal ACh levels in a manner that is independent of age. However, compared to isoflurane, desflurane is associated with a slower decrease in and a faster restoration of hippocampal ACh levels following anesthesia in this rat model of aging. Hence, in the aged, the administration of age-adjusted equipotent doses of an inhalational anesthetic with low blood and tissue solubility, such as desflurane, may provide a viable pharmacotherapeutic strategy for minimizing the duration of the attenuation of hippocampal cholinergic outflow observed following anesthesia.
使用脑微透析技术,在年轻(12-16 周龄)和老年(16-18 月龄)Fischer 344 大鼠中,观察了年龄校正等效剂量的异氟烷(Iso)和地氟烷(Des)对海马乙酰胆碱(ACh)水平的差异影响。在 1 个最低肺泡有效浓度(MAC)下,80min 的异氟烷和地氟烷暴露导致两个年龄组的海马 ACh 水平都出现类似的最大下降:老年大鼠的基线值下降到 36.3+/-13.9%(Iso)和 28.6+/-12.9%(Des),而年轻大鼠的基线值下降到 32.5+/-18.7%(Iso)和 29.6+/-12.5%(Des)。与异氟烷相比,地氟烷在两个年龄组中均延迟了这种最大降低的发生。此外,在老年大鼠麻醉结束后,地氟烷比异氟烷更快地使海马 ACh 水平恢复到对照水平(20-40min 内),而异氟烷则需要(60-80min 内)。这些数据表明,年龄校正等效剂量的异氟烷和地氟烷以与年龄无关的方式产生类似的最大海马 ACh 水平降低。然而,与异氟烷相比,在这个衰老大鼠模型中,与麻醉后海马 ACh 水平的降低速度较慢且恢复速度较快相关。因此,在老年患者中,给予具有低血液和组织溶解度的年龄校正等效剂量的吸入性麻醉剂,如地氟烷,可能是一种可行的药物治疗策略,可最大限度地减少麻醉后观察到的海马胆碱能输出减弱的持续时间。