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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
Author(s) -
KIM K. O.,
CHOE G.,
CHUNG S. H.,
KIM C. S.
Publication year - 2008
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2007.01534.x
Subject(s) - diazoxide , medicine , potassium channel opener , ischemia , anesthesia , spinal cord , h&e stain , potassium channel , reperfusion injury , staining , pathology , psychiatry , insulin
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.