title: Isoflurane preconditioning protects motor neurons from spinal cord ischemia: its dose-response effects and activation of mitochondrial adenosine triphosphate-dependent potassium channel.
abstract: We examined in a rabbit model of transient spinal cord ischemia (SCI) whether isoflurane (Iso) preconditioning induces ischemic tolerance to SCI in a dose-response manner, and whether this effect is dependent on mitochondrial adenosine triphosphate-dependent potassium (K(ATP)) channel. Eighty-six rabbits were randomly assigned to 10 groups: Control group (n=8) received no pretreatment. Ischemic preconditioning (IPC) group (n=8) received 5 min of IPC 30 min before SCI. The Iso 1, Iso 2 and Iso 3 groups (n=10, 9, 8) underwent 30 min of 1.05, 2.1 and 3.15% Iso inhalation commencing 45 min before SCI. The Iso 1HD, Iso 2HD and Iso 3HD groups (n=9, 9, 8) each received a specific mitochondrial K(ATP) channel blocker, 5-hydroxydecanoic acid (5HD, 20mg/kg), 5 min before each respective Iso inhalation. The 5HD group (n=8) received 5HD without Iso inhalation. The sham group (n=9) had no SCI. SCI was produced by infra-renal aortic occlusion via the inflated balloon of a Swan-Ganz catheter for 20 min. The Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and more viable motor nerve cells (VMNCs) in the anterior spinal cord 72 h after reperfusion than the control group (p<0.05). Iso 3 group showed a better neurologic outcome and more VMNCs than Iso 1 group (p<0.05). And, the Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and higher VMNC numbers than the corresponding Iso 1HD, Iso 2HD and Iso 3HD groups (p<0.05). This study demonstrates that Iso preconditioning protects the spinal cord against neuronal damage due to SCI in a dose-response manner via the activation of mitochondrial K(ATP) channels.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Seongnam 463-707, Republic of Korea.
authors.forename: Hee-Pyoung
authors.initials: HP
authors.lastname: Park
authors.forename: Young-tae
authors.initials: YT
authors.lastname: Jeon
authors.forename: Jung-won
authors.initials: JW
authors.lastname: Hwang
authors.forename: Hoon
authors.initials: H
authors.lastname: Kang
authors.forename: Seung-Woon
authors.initials: SW
authors.lastname: Lim
authors.forename: Chong-Sung
authors.initials: CS
authors.lastname: Kim
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Oh
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019194:Ischemic Preconditioning / Q000379:methods*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D013116:Spinal Cord / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D007530:Isoflurane