Patel P M, Drummond J C, Cole D J, Kelly P J, Watson M
Department of Anesthesiology, University of California-San Diego and the Department of Veterans Affairs, Veterans Affairs Medical Center, 92161, USA.
Anesth Analg. 1998 Apr;86(4):773-80. doi: 10.1097/00000539-199804000-00018.
Repetitive transient ischemic depolarizations (IDs) during focal cerebral ischemia are thought to contribute to ischemic damage. Isoflurane and pentobarbital reduce injury (versus the nonanesthetized state) after focal cerebral ischemia. The mechanism by which these drugs reduce injury is not known. This protective effect might be mediated by a reduction in the number of IDs. We measured the frequency of IDs during focal cerebral ischemia in animals anesthetized with isoflurane or pentobarbital and compared it with that in N2O/fentanyl anesthetized animals and in animals in which the N-methyl-D-aspartate receptor antagonist MK801 (dizocilpine) was given. Focal cerebral ischemia was induced by the occlusion of the middle cerebral artery for a period of 2 h. Cortical infarct volumes were determined after 3 h of reperfusion by image analysis of 2,3,5-triphenyl tetrazolium-stained coronal brain sections. The infarct volume was significantly greater in the N2O/fentanyl group than in the other three groups. Infarct volumes in the isoflurane, pentobarbital, and MK801 groups were similar. The frequency of IDs was significantly greater in the N2O/fentanyl group than in the other three groups, and was the least in the MK801 group. There was a direct correlation between the number of IDs and the volume of tissue injury. The data indicate that the protective effect of isoflurane and pentobarbital might, in part, be determined by their ability to reduce IDs during focal ischemia. However, the observation that the infarct volume was similar in the MK801, isoflurane, and pentobarbital groups, despite a greater frequency of IDs in the latter two groups, suggests that mechanisms other than a simple reduction in the number of IDs probably also play a role in anesthetic-mediated cerebral protection.
Transient ischemic depolarizations during focal ischemia contribute to brain injury. Both isoflurane and pentobarbital reduced the frequency of these depolarizations. Isoflurane- and pentobarbital-mediated reduction in the frequency of depolarizations might, in part, mediate the previously documented neuroprotective effect of these drugs.
局灶性脑缺血期间的重复性短暂性缺血性去极化（IDs）被认为会导致缺血性损伤。异氟烷和戊巴比妥可减轻局灶性脑缺血后的损伤（与未麻醉状态相比）。这些药物减轻损伤的机制尚不清楚。这种保护作用可能是通过减少IDs的数量来介导的。我们测量了用异氟烷或戊巴比妥麻醉的动物在局灶性脑缺血期间IDs的频率，并将其与用氧化亚氮/芬太尼麻醉的动物以及给予N-甲基-D-天冬氨酸受体拮抗剂MK801（地佐环平）的动物的频率进行比较。通过闭塞大脑中动脉2小时诱导局灶性脑缺血。再灌注3小时后，通过对2,3,5-三苯基四氮唑染色的冠状脑切片进行图像分析来确定皮质梗死体积。氧化亚氮/芬太尼组的梗死体积明显大于其他三组。异氟烷、戊巴比妥和MK801组的梗死体积相似。氧化亚氮/芬太尼组中IDs的频率明显高于其他三组，而MK801组中IDs的频率最低。IDs的数量与组织损伤的体积之间存在直接相关性。数据表明，异氟烷和戊巴比妥的保护作用可能部分取决于它们在局灶性缺血期间减少IDs的能力。然而，尽管后两组中IDs的频率较高，但MK801、异氟烷和戊巴比妥组的梗死体积相似，这一观察结果表明，除了简单减少IDs数量之外的机制可能也在麻醉介导的脑保护中起作用。
局灶性缺血期间的短暂性缺血性去极化会导致脑损伤。异氟烷和戊巴比妥都降低了这些去极化的频率。异氟烷和戊巴比妥介导的去极化频率降低可能部分介导了这些药物先前记录的神经保护作用。
