Delayed pharmacological pre-conditioning effect of mitochondrial ATP-sensitive potassium channel opener on neurologic injury in a rabbit model of spinal cord ischemia.
BACKGROUND
Diazoxide, pharmacological openers of mitochondrial ATP-sensitive potassium channels have been shown to induce early pre-conditioning in the spinal cord. Here, the authors investigated whether diazoxide also induce delayed pre-conditioning and thereby reduce neurologic complications using a rabbit model of spinal cord ischemia.


METHODS
Infrarenal blood flow was interrupted for 20 min in 21 rabbits. Non-treated control animals received no pre-treatment. Diazoxide (5 mg/kg) were given 48 h before 20 min ischemia in the 48-h DZ group, whereas 15-min DZ group received diazoxide (5 mg/kg) 15 min before 20-min ischemia. Neurological functions were evaluated using Johnson scores for 3 days after reperfusion, after which, spinal cords were procured for hematoxylin and eosin staining for cell counting.


RESULTS
Johnson scores revealed a marked improvement in both the diazoxide-treated groups vs. the non-treated control group at 3, 24, 48, and 72 h after reperfusion (P<0.01). The histologic changes were proportional to the Johnson scores, with better preservation of motor neuron numbers in the animals of the 48-h DZ and 15-min DZ group relative to the non-treated controls (81+/-12, 90+/-10, 50+/-23 motor neurons, respectively, P<0.01). No difference was found between the 48-h DZ group and 15-min DZ group with respect to the Johnson scores or neuron numbers.


CONCLUSIONS
The study demonstrates that pre-treatment with diazoxide 48 h before ischemia, induce delayed pharmacological pre-conditioning, thereby significantly improving clinical neurologic scores and histologic findings in this animal model.
Kim
K O
KO
Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Korea. pissces@medimail.co.kr
Choe
G
G
Chung
S H
SH
Kim
C S
CS
D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D001784:Blood Gas Analysis; D003981:Diazoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D019194:Ischemic Preconditioning / Q000379:methods*; D007649:Ketamine / Q000008:administration & dosage; D008297:Male; D009460:Neurologic Examination / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000494:pharmacology*; D011817:Rabbits; D011897:Random Allocation; D012965:Sodium Chloride / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D000700:Analgesics; D018696:Neuroprotective Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D012965:Sodium Chloride; D007649:Ketamine; D003981:Diazoxide