Preconditioning with isoflurane produces dose-dependent neuroprotection via activation of adenosine triphosphate-regulated potassium channels after focal cerebral ischemia in rats.
In this study, we determined whether repeated brief isoflurane (Iso) anesthesia induces ischemic tolerance to focal cerebral ischemia in a dose-response manner and whether the effect is dependent on adenosine triphosphate-regulated potassium channels. In Experiment 1, 40 rats were randomly assigned to 4 groups: control animals received 100% oxygen 1 h/d for 5 days, whereas the isoflurane (Iso)1, Iso2, and Iso3 groups received 0.75%, 1.5%, or 2.25% Iso in oxygen 1 h/d for 5 days. In Experiment 2, 36 rats were randomly assigned to 4 groups: controls received 100% oxygen 1 h/d for 5 days; animals in the Iso and I+G (Iso+glibenclamide) groups received 2% Iso in oxygen 1 h/d for 5 days, and the I+G group received glibenclamide (GLB) (5 mg/kg intraperitoneally) before each Iso pretreatment. Animals in the GLB group received GLB (5 mg/kg intraperitoneally) once a day for 5 days. Twenty-four hours after the last pretreatment, the right middle cerebral artery was occluded for 120 min. Neurologic deficit scores (NDS) and brain infarct volumes were evaluated at 24 h. The NDS and infarct volumes of Iso2 and Iso3 were less than those of the controls (P < 0.05). The infarct volume in Iso3 was smaller than in Iso2 (P < 0.05). The NDS and infarct volume in the Iso group were less than in the control and I+G groups (P < 0.05). There was no statistical difference among the control, I+G, and GLB groups. The study demonstrated that repeated Iso anesthesia induces ischemic tolerance in rats in a dose-response manner. GLB, an adenosine triphosphate-regulated potassium channel blocker, abolished the tolerance induced by Iso.


CONCLUSIONS
Brief isoflurane anesthesia induces ischemic tolerance in the brain. The effect was found to be dose dependent in a rat focal cerebral ischemia model. Ischemic tolerance induced by isoflurane preconditioning is dependent on activation of adenosine triphosphate-regulated potassium channels.
Xiong
Lize
L
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. lxiong@fmmu.edu.cn
Zheng
Yu
Y
Wu
Mingchun
M
Hou
Lichao
L
Zhu
Zhenghua
Z
Zhang
Xijing
X
Lu
Zhihong
Z
D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001831:Body Temperature / Q000502:physiology; D020520:Brain Infarction / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D007530:Isoflurane / Q000494:pharmacology*; D054086:KATP Channels; D008297:Male; D018696:Neuroprotective Agents; D015221:Potassium Channels / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology
D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation; D007004:Hypoglycemic Agents; D054086:KATP Channels; D018696:Neuroprotective Agents; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D007530:Isoflurane; D005905:Glyburide