title: Isoflurane produces delayed preconditioning against spinal cord ischemic injury via release of free radicals in rabbits.
abstract: BACKGROUND
  Whether isoflurane preconditioning produces delayed neuroprotection in the spinal cord is unclear. The authors tested the hypothesis that isoflurane produces delayed preconditioning against spinal cord ischemic injury and, further, that the beneficial effect is dependent on free radicals.
  
  
  METHODS
  In experiment 1, 63 rabbits were randomly assigned to seven groups (n = 9 each): Animals in the control group only underwent spinal cord ischemia without pretreatment; animals in the Iso24h, Iso48h, and Iso72h groups received 40 min of 1.0 minimum alveolar concentration isoflurane in 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia; animals in the O2 24h, O2 48h, and O2 72h groups received 40 min of 100% oxygen each day for 5 consecutive days, with the last pretreatment at 24, 48, and 72 h, respectively, before spinal cord ischemia. In experiment 2, 48 rabbits were randomly assigned into four groups (n = 12 each): Animals in the O2 and Iso groups received 3 ml/kg saline intraperitoneally 1 h before each session of oxygen pretreatment and isoflurane pretreatment, respectively. In the DMTU+Iso and DMTU+O2 groups, 10% dimethylthiourea (DMTU, a potent free radical scavenger) dissolved in saline (3 ml/kg) was administered at the same time point. Twenty-four hours after the last pretreatment, animals were subjected to spinal cord ischemia. Spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, neurologic function and histopathology of the spinal cord were examined.
  
  
  RESULTS
  In experiment 1, the neurologic and histopathologic outcomes in the Iso24h and Iso48h groups were better than those in the control group (P < 0.005 for each comparison); the neurologic and histopathologic outcomes in the control group showed no significant differences in comparison with the O2 24h, O2 48h, O2 72h, and Iso72h groups (P > 0.05 for each comparison). In experiment 2, the neurologic and histopathologic outcomes in the Iso group were better than those in the DMTU+Iso, O2, and DMTU+O2 groups (P < 0.01 for each comparison); there were no significant differences in the neurologic and histopathologic outcomes among the DMTU+Iso, O2, and DMTU+O2 groups (P > 0.05 for each comparison).
  
  
  CONCLUSIONS
  Isoflurane produces delayed preconditioning against spinal cord ischemic injury, and the beneficial effect may be dependent on the release of free radicals.
authors.affiliation: Department of Pharmacology, Zhongshan Medical College, Guangzhou, China.
authors.forename: Hanfei
authors.initials: H
authors.lastname: Sang
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.forename: Pengxin
authors.initials: P
authors.lastname: Qiu
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wang
authors.forename: Guangmei
authors.initials: G
authors.lastname: Yan
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D016166:Free Radical Scavengers / Q000008:administration & dosage; D005609:Free Radicals / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000008:administration & dosage; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020760:Spinal Cord Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013890:Thiourea / Q000008:administration & dosage / Q000031:analogs & derivatives; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D016166:Free Radical Scavengers; D005609:Free Radicals; C038983:1,3-dimethylthiourea; D007530:Isoflurane; D013890:Thiourea; D010100:Oxygen