Wang Y, Kikuchi T, Sakai M, Wu J L, Sato K, Okumura F
Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama, Japan.
Acta Anaesthesiol Scand. 2000 Jan;44(1):112-7. doi: 10.1034/j.1399-6576.2000.440120.x.
We sometimes encounter impairment of learning and memory after general anesthesia in elderly patients. The aim of this study was to examine age-related modifications of the effects of ketamine and propofol on rat hippocampal acetylcholine (ACh) release because hippocampal cholinergic neurons are supposed to be involved in learning and memory.
The experiments were performed on male Wistar young rats (2 months old) and old rats (18 months old), using in vivo brain microdialysis technique under freely moving condition. After initial sampling of three collections, test drugs were administered. The ACh release was determined by the HPLC-ECD method.
In old rats, the hippocampal basal ACh release was significantly lower than in young rats. Ketamine (25 and 50 mg kg(-1) i.p.) increased and propofol (25 and 50 mg kg(-1) i.p.) decreased the hippocampal ACh release in both young and old rats. Furthermore, ketamine 50 mg kg(-1) i.p. (anesthetic dose) produced facilitatory effects on the hippocampal ACh release in young rats (193% of the basal release), while in old rats the same dose of ketamine i.p. produced more pronounced facilitatory effects on the hippocampal ACh release (317% of the basal release). On the other hand, propofol 50 mg kg(-1) i.p. (anesthetic dose) produced inhibitory effects on the hippocampal ACh release in young rats (56% of control) and in old rats (77% of control). Although the maximal inhibitory peak effects of propofol 50 mg kg(-1) i.p. did not differ significantly between young rats and old rats, decrease of the hippocampal ACh release in old rats persisted longer than in young rats.
Ketamine produced more pronounced facilitatory effects on the hippocampal ACh release in old rats, as compared with young rats. On the other hand, propofol has inhibitory effects on the hippocampal ACh release in young and old rats. The aging process may suppress the ability to recover from the inhibitory anesthetic state induced by propofol.
我们有时会遇到老年患者全身麻醉后学习和记忆受损的情况。本研究的目的是研究氯胺酮和丙泊酚对大鼠海马乙酰胆碱（ACh）释放影响的年龄相关变化，因为海马胆碱能神经元被认为与学习和记忆有关。
实验在雄性Wistar幼鼠（2个月大）和老年大鼠（18个月大）身上进行，在自由活动条件下使用体内脑微透析技术。在最初采集三次样本后，给予受试药物。通过高效液相色谱-电化学检测法测定ACh释放量。
老年大鼠海马基础ACh释放量显著低于幼鼠。氯胺酮（腹腔注射25和50 mg kg⁻¹）增加了幼鼠和老年大鼠海马ACh的释放，丙泊酚（腹腔注射25和50 mg kg⁻¹）则降低了其释放。此外，氯胺酮腹腔注射50 mg kg⁻¹（麻醉剂量）对幼鼠海马ACh释放产生促进作用（为基础释放量的193%），而在老年大鼠中，相同剂量的氯胺酮腹腔注射对海马ACh释放产生更明显的促进作用（为基础释放量的317%）。另一方面，丙泊酚腹腔注射50 mg kg⁻¹（麻醉剂量）对幼鼠（为对照组的56%）和老年大鼠（为对照组的77%）海马ACh释放产生抑制作用。尽管丙泊酚腹腔注射50 mg kg⁻¹的最大抑制峰值效应在幼鼠和老年大鼠之间无显著差异，但老年大鼠海马ACh释放量的降低持续时间比幼鼠更长。
与幼鼠相比，氯胺酮对老年大鼠海马ACh释放产生更明显的促进作用。另一方面，丙泊酚对幼鼠和老年大鼠海马ACh释放均有抑制作用。衰老过程可能会抑制从丙泊酚诱导的抑制性麻醉状态中恢复的能力。
