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Delayed pharmacological pre-conditioning effect of mitochondrial ATP-sensitive potassium channel opener on neurologic injury in a rabbit model of spinal cord ischemia

Cited 5 time in Web of Science Cited 4 time in Scopus
Authors
Kim, Kyoung Ok; Choe, G; Chung, S H; Kim, C S
Issue Date
2007-11-17
Publisher
Acta Anaesthesiol Scand
Citation
Acta Anaesthesiol Scand. 2008 Feb;52(2):236-42. Epub 2007 Nov 13.
Keywords
Analgesics/administration & dosageAnimalsBlood Gas AnalysisDiazoxide/*pharmacologyDisease Models, AnimalIschemic Preconditioning/*methodsKetamine/administration & dosageMaleNeurologic Examination/drug effectsNeuroprotective Agents/*pharmacologyPotassium Channels/*pharmacologyRabbitsRandom AllocationSodium Chloride/administration & dosageSpinal Cord/drug effects/physiopathologySpinal Cord Ischemia/*drug therapy/physiopathologyTime Factors
Abstract
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.
ISSN
1399-6576 (Electronic)
1399-6576 (Linking)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18005376

https://hdl.handle.net/10371/45517
DOI
https://doi.org/10.1111/j.1399-6576.2007.01534.x
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College of Medicine/School of Medicine (의과대학/대학원)Anesthesiology and Pain Medicine (마취통증의학전공)Journal Papers (저널논문_마취통증의학전공)
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