Schultz J A, Hoffman W E, Albrecht R F
Anesthesiology Department, University of Illinois, Chicago.
Anesthesiology. 1993 Jul;79(1):114-21. doi: 10.1097/00000542-199307000-00017.
It has been suggested that anesthetics may protect the brain during incomplete cerebral ischemia by inhibition of sympathetic activity. This study evaluated whether physostigmine may increase plasma epinephrine and norepinephrine during carotid occlusion with hypotension and worsen ischemic outcome in rats and if this effect could be reversed by dexmedetomidine, an alpha 2-adrenergic agonist.
Anesthesia was maintained with fentanyl (25 micrograms.kg-1.h-1) combined with 70% N2O ventilation in oxygen. Ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 30 mmHg for 30 min. Plasma epinephrine and norepinephrine were measured during ischemia. Neurologic outcome was evaluated for 3 days after ischemia. There were three groups: control (n = 10), physostigmine (1 mg/kg intraperitoneal 3 min before the start of ischemia, n = 10), and physostigmine plus dexmedetomidine (100 micrograms/kg intraperitoneally 15 min before the start of ischemia, n = 10). Brain tissue glutamate concentrations were measured by microdialysis in separate studies.
Compared to control rats, physostigmine increased plasma epinephrine and norepinephrine 10-fold and worsened neurologic outcome. The increases in epinephrine and norepinephrine were blocked by dexmedetomidine before treatment, and neurologic outcome was improved. Outcome was not correlated with blood glucose during ischemia (r = 0.11). Ischemia increased brain tissue glutamate from < 100 microM to 400 microM during ischemia. This increase was not altered by physostigmine treatment.
These results suggest that physostigmine worsens ischemic outcome by a mechanism that is associated with increases in plasma epinephrine and norepinephrine.
有研究表明，麻醉剂可能通过抑制交感神经活动在不完全性脑缺血期间保护大脑。本研究评估了毒扁豆碱是否会在大鼠颈动脉闭塞伴低血压期间增加血浆肾上腺素和去甲肾上腺素，并恶化缺血结局，以及这种效应是否可被α2-肾上腺素能激动剂右美托咪定逆转。
采用芬太尼（25微克·千克-1·小时-1）联合70%氧化亚氮在氧气中通气维持麻醉。通过右颈动脉结扎联合出血性低血压至30 mmHg持续30分钟来制造缺血。在缺血期间测量血浆肾上腺素和去甲肾上腺素。缺血后3天评估神经功能结局。分为三组：对照组（n = 10）、毒扁豆碱组（缺血开始前3分钟腹腔注射1毫克/千克，n = 10）、毒扁豆碱加右美托咪定组（缺血开始前15分钟腹腔注射100微克/千克，n = 10）。在单独的研究中通过微透析测量脑组织谷氨酸浓度。
与对照大鼠相比，毒扁豆碱使血浆肾上腺素和去甲肾上腺素增加了10倍，并恶化了神经功能结局。肾上腺素和去甲肾上腺素的增加在治疗前被右美托咪定阻断，神经功能结局得到改善。结局与缺血期间的血糖无关（r = 0.11）。缺血期间脑组织谷氨酸从<100微摩尔/升增加到400微摩尔/升。这种增加不受毒扁豆碱治疗的影响。
这些结果表明，毒扁豆碱通过与血浆肾上腺素和去甲肾上腺素增加相关的机制恶化缺血结局。
