Department of Anesthesia, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA.
Anesth Analg. 2010 May 1;110(5):1412-8. doi: 10.1213/ANE.0b013e3181d6c0ae. Epub 2010 Mar 19.
We performed experiments to test whether isoflurane pretreatment produces vascular effects, especially at the levels of arterioles and capillaries affecting regional cerebral blood flow (rCBF), O(2) supply and consumption, or capillary permeability in focal cerebral ischemia. Because inducible nitric oxide synthase (iNOS) was implicated as one of the mechanisms of isoflurane preconditioning, the effect of iNOS inhibition on rCBF was also studied.
Twenty-four hours before middle cerebral artery (MCA) occlusion, rats were pretreated with 2% isoflurane for 30 minutes using an endotracheal tube and mechanical ventilation for the isoflurane preconditioned (IsoPC) group. For the group of iNOS inhibition, aminoguanidine 200 mg/kg was injected IP 30 minutes before isoflurane pretreatment. One hour after MCA occlusion, rCBF was measured using (14)C-iodoantipyrine autoradiography. Alternate slices of the tissue were used to determine arteriolar and venular O(2) saturation using cryo microspectrophotometry. Capillary permeability was determined by measuring the transfer coefficient (Ki) of (14)C-alpha-aminoisobutyric acid. Additional measurements of rCBF were performed at 3 hours after MCA occlusion.
MCA occlusion decreased rCBF and O(2) consumption and increased Ki in both the control and the IsoPC groups at 1 hour after MCA occlusion. In the ischemic cortex (IC), the rCBF and O(2) consumption were significantly greater in the IsoPC group than in the control group (+40% and +41%, respectively), but they were similar in the contralateral cortex between the 2 groups. There was no difference in Ki between the groups in the IC or in the contralateral cortex. The increase of rCBF in the IC (+50%) was sustained in the IsoPC group at 3 hours after MCA occlusion. With iNOS inhibition, the increase of rCBF in the IC with isoflurane pretreatment became insignificant.
Our data demonstrate that isoflurane pretreatment improved rCBF and increased the regional O(2) supply and consumption in the focal ischemic area but did not affect capillary permeability during the early stage of focal cerebral ischemia. The isoflurane-induced increase in rCBF in the ischemic area became insignificant with inhibition of iNOS.
我们进行了实验以测试异氟醚预处理是否会产生血管效应，特别是在影响局部脑血流 (rCBF)、O2 供应和消耗或局灶性脑缺血毛细血管通透性的小动脉和毛细血管水平。因为诱导型一氧化氮合酶 (iNOS) 被认为是异氟醚预处理的机制之一，所以还研究了 iNOS 抑制对 rCBF 的影响。
在大脑中动脉 (MCA) 闭塞前 24 小时，通过气管内管和机械通气用 2%异氟醚对大鼠进行预处理 30 分钟，以进行异氟醚预处理组（IsoPC 组）。对于 iNOS 抑制组，在异氟醚预处理前 30 分钟，通过腹腔内注射氨基胍 200mg/kg。MCA 闭塞后 1 小时，通过 14C-碘安替比林放射自显影术测量 rCBF。使用冷冻微分光光度法测定组织的交替切片中小动脉和小静脉的氧饱和度。通过测量 14C-α-氨基异丁酸的转移系数 (Ki) 来确定毛细血管通透性。在 MCA 闭塞后 3 小时进行了 rCBF 的额外测量。
MCA 闭塞后 1 小时，在对照组和 IsoPC 组中，rCBF 和 O2 消耗均降低，Ki 值增加。在缺血皮质（IC）中，与对照组相比，IsoPC 组的 rCBF 和 O2 消耗明显更高（分别增加 40%和 41%），但两组间对侧皮质的 rCBF 和 O2 消耗相似。IC 和对侧皮质之间的 Ki 值在两组之间没有差异。在 MCA 闭塞后 3 小时，IsoPC 组 IC 中的 rCBF 增加持续存在。用 iNOS 抑制后，用异氟醚预处理增加 IC 中的 rCBF 变得不显著。
我们的数据表明，异氟醚预处理可改善 rCBF，并增加局灶性缺血区的区域 O2 供应和消耗，但在局灶性脑缺血的早期阶段不影响毛细血管通透性。用 iNOS 抑制剂抑制后，异氟醚预处理引起的缺血区 rCBF 增加变得不显著。
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