Homi H Mayumi, Mixco Javier M, Sheng Huaxin, Grocott Hilary P, Pearlstein Robert D, Warner David S
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Anesthesiology. 2003 Nov;99(5):1145-51. doi: 10.1097/00000542-200311000-00022.
Volatile anesthetics provide protection in experimental models of global cerebral ischemia. To date, all models evaluated have included profound systemic arterial hypotension as a component of the ischemic insult. This study was designed to determine if isoflurane protection persists in a global insult devoid of hypotension.
C57BL/6J mice having a high incidence of posterior communicating artery atresia were anesthetized with isoflurane (1.2%) or fentanyl/N2O and subjected to bilateral carotid artery occlusion for 15 min or 20 min with normotension (80-110 mmHg mean arterial pressure) or for 10 min with hypotension (35 mmHg mean arterial pressure). Three days later, neurologic function and histologic damage were assessed. Other mice underwent measurement of intraischemic cerebral blood flow (4-iodo-N-methyl-[14C]antipyrine autoradiography) or plasma norepinephrine.
Isoflurane reduced the percentage of hippocampal CA1 dead neurons (e.g., 10 min bilateral carotid occlusion + hypotension: 43 +/- 18 (isoflurane) vs. 67 +/- 20 (fentanyl/N2O), P = 0.003; 20 min bilateral carotid occlusion + normotension: 49 +/- 27 (isoflurane) vs. 71 +/- 22 (fentanyl/N2O), P = 0.003). Isoflurane also reduced CA3 damage and improved neurologic function under all conditions. Intraischemic forebrain blood flow was similar during bilateral carotid occlusion plus normotension for the two anesthetic states. Plasma norepinephrine values were greater when hypotension was added to the ischemic insult.
Isoflurane resulted in improved neurologic function and reduced histologic damage regardless of the presence or absence of systemic hypotension during the ischemic insult. This indicates that beneficial effects of isoflurane are most likely attributable to direct effects at the neuronal level as opposed to indirect effects resulting from interactions with profound hypotension.
挥发性麻醉药在全脑缺血的实验模型中具有保护作用。迄今为止，所有评估的模型都将严重的体循环动脉低血压作为缺血性损伤的一个组成部分。本研究旨在确定异氟烷在无低血压的全脑损伤中是否仍具有保护作用。
对后交通动脉闭锁发生率高的C57BL/6J小鼠，用异氟烷（1.2%）或芬太尼/笑气麻醉，在血压正常（平均动脉压80 - 110 mmHg）情况下双侧颈动脉闭塞15分钟或20分钟，或在低血压（平均动脉压35 mmHg）情况下双侧颈动脉闭塞10分钟。三天后，评估神经功能和组织学损伤。其他小鼠进行缺血期间脑血流量测量（4-碘-N-甲基-[14C]安替比林放射自显影）或血浆去甲肾上腺素测量。
异氟烷降低了海马CA1区死亡神经元的百分比（例如，双侧颈动脉闭塞10分钟 + 低血压：43 ± 18（异氟烷）对67 ± 20（芬太尼/笑气），P = 0.003；双侧颈动脉闭塞20分钟 + 血压正常：49 ± 27（异氟烷）对71 ± 22（芬太尼/笑气），P = 0.003）。在所有情况下，异氟烷还减少了CA3区损伤并改善了神经功能。在双侧颈动脉闭塞加血压正常期间，两种麻醉状态下的缺血前脑血流量相似。当缺血性损伤伴有低血压时，血浆去甲肾上腺素值更高。
无论缺血性损伤期间是否存在体循环低血压，异氟烷均可改善神经功能并减少组织学损伤。这表明异氟烷的有益作用很可能归因于其在神经元水平的直接作用，而非与严重低血压相互作用产生的间接作用。
