Kon S, Imai M, Inaba H
Department of Anesthesiology, Kimitsu Chuo Hospital, Chiba, Japan.
Anesthesiology. 1997 Jan;86(1):128-36. doi: 10.1097/00000542-199701000-00017.
Ischemia-hypoxia followed by reperfusion and reoxygenation injures cells and organs. Previous studies have indicated that isoflurane may protect organs from ischemia-reperfusion or hypoxia-reoxygenation. This study investigated the ability of isoflurane to protect the liver from hypoxia-reoxygenation injury and the mechanisms of this phenomenon.
The isolated liver was perfused at a constant pressure of 12 cm H2O with a modified Krebs-Ringer-bicarbonate solution saturated with a 95% oxygen/5% carbon dioxide gas mixture. Hypoxic perfusion produced by decreasing the oxygen concentration in the gas mixture to 10% was followed by perfusion at 95% oxygen for 60 min. Viability of the liver was assessed by lactate dehydrogenase release from the liver. Isoflurane at 0.5, 1, and 2 minimum alveolar concentration was administered to assess the effect of isoflurane on hypoxia-reperfusion injury. To determine the effect of isoflurane on extracellular generation of superoxide in the liver, the reduction of ferricytochrome c with or without superoxide dismutase was measured.
Lactate dehydrogenase release was transiently but dramatically increased by reoxygenation and significantly attenuated by 1 and 2 minimum alveolar concentration of isoflurane. Suppression of Kupffer cells with gadolinium chloride also attenuated the lactate dehydrogenase release. Isoflurane significantly reduced the superoxide generation on reperfusion.
The results show that isoflurane protected the liver from an early reoxygenation injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory effects of isoflurane on the injury may involve suppression of extracellular superoxide generation during reoxygenation.
缺血缺氧后再灌注和复氧会损伤细胞和器官。先前的研究表明，异氟烷可能保护器官免受缺血再灌注或缺氧复氧损伤。本研究调查了异氟烷保护肝脏免受缺氧复氧损伤的能力及其机制。
将离体肝脏以12 cm H2O的恒定压力用含95%氧气/5%二氧化碳混合气体饱和的改良krebs - ringer -碳酸氢盐溶液灌注。通过将混合气体中的氧气浓度降至10%产生缺氧灌注，随后以95%氧气灌注60分钟。通过测定肝脏中乳酸脱氢酶的释放来评估肝脏的活力。给予0.5、1和2最低肺泡浓度的异氟烷，以评估异氟烷对缺氧再灌注损伤的影响。为了确定异氟烷对肝脏细胞外超氧化物生成的影响，测量了有无超氧化物歧化酶时细胞色素c的还原情况。
复氧使乳酸脱氢酶释放短暂但显著增加，而1和2最低肺泡浓度的异氟烷可显著减轻这种增加。用氯化钆抑制库普弗细胞也可减轻乳酸脱氢酶的释放。异氟烷显著减少了再灌注时超氧化物的生成。
结果表明，异氟烷可保护肝脏免受可能由库普弗细胞介导的早期复氧损伤。异氟烷对损伤的抑制作用机制可能涉及抑制复氧期间细胞外超氧化物的生成。
