Sevoflurane preconditioning induces rapid ischemic tolerance against spinal cord ischemia/reperfusion through activation of extracellular signal-regulated kinase in rabbits.
BACKGROUND
The protective effect of sevoflurane preconditioning against spinal cord ischemia/reperfusion (I/R) is unclear. We designed this study to investigate whether sevoflurane preconditioning could induce rapid ischemic tolerance to the spinal cord in a rabbit model of transient spinal cord ischemia and how the role of extracellular signal-regulated kinase (ERK) is involved.


METHODS
To test whether preconditioning with sevoflurane induces rapid ischemic tolerance, New Zealand White male rabbits were randomly assigned to three groups. Animals in the Sev group received preconditioning with 3.7% sevoflurane (1.0 minimum alveolar anesthetic concentration) in 96% oxygen for 30 min, whereas animals in the O(2) group serving as controls inhaled only 96% oxygen for 30 min. The Sham group received the same anesthesia and surgical preparation but no preconditioning or spinal cord I/R. To evaluate the role of ERK activation in sevoflurane preconditioning, rabbits were randomly assigned to four groups. U0126, an ERK inhibitor, was administered IV 20 min before the beginning of preconditioning in the U0126 + O(2) and U0126 + Sev groups. Dimethylsulfoxide was administered IV at the same time in the vehicle + O(2) and vehicle + Sev groups. At 1 h after preconditioning, the animals were subjected to spinal cord I/R induced by infrarenal aorta occlusion. All animals were assessed at 48 h after reperfusion with modified Tarlov criteria, and the spinal cord segments (L5) were harvested for histopathological examination, TUNEL staining, and Western blot of phosphor-ERK1/2.


RESULTS
The animals in the Sev group had higher neurological scores and more normal motor neurons than those in the O(2) group (P < 0.01 for each comparison). Compared with vehicle + Sev group, the U0126 + Sev group had worse neurological outcomes, fewer viable neurons, more apoptotic neurons, and significantly decreased ERK1/2 phosphorylation (P <or= 0.01 for each comparison). There were no significant differences in the outcomes among vehicle + O(2), U0126 + O(2), and U0126 + Sev groups.


CONCLUSIONS
This study demonstrates that sevoflurane preconditioning induces rapid tolerance to spinal cord I/R in rabbits, and the tolerance is possibly mediated through the activation of ERK. These data suggest that sevoflurane preconditioning might provide a new practical method for protecting perioperative spinal cord I/R.
Ding
Qian
Q
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
Wang
Qiang
Q
Deng
Jiao
J
Gu
Qiuhan
Q
Hu
Sheng
S
Li
Yang
Y
Su
Binxiao
B
Zeng
Yi
Y
Xiong
Lize
L
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal; D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D002470:Cell Survival; D003250:Constriction; D004195:Disease Models, Animal; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009460:Neurologic Examination; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000077149:Sevoflurane; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D013997:Time Factors
D018685:Anesthetics, Inhalation; D002070:Butadienes; D008738:Methyl Ethers; D009570:Nitriles; D047428:Protein Kinase Inhibitors; C113580:U 0126; D000077149:Sevoflurane; D048049:Extracellular Signal-Regulated MAP Kinases