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Attenuation of spinal cord ischemia-reperfusion injury by specific α-2a receptor activation with dexmedetomidine

2012; Elsevier BV; Volume: 56; Issue: 5 Linguagem: Inglês

10.1016/j.jvs.2012.04.012

1097-6809

Marshall T. Bell, Ferenc Puskás, Phillip D. Smith, Viktor A. Ágoston, David A. Fullerton, Xianzhong Meng, Michael J. Weyant, T. Brett Reece,

Anesthesia and Neurotoxicity Research

BackgroundDespite surgical adjuncts, paralysis remains a devastating complication after thoracoabdominal aortic interventions. Dexmedetomidine, a selective α-2a agonist commonly used for sedation in the critical care setting, has been shown to have protective effects against ischemia-reperfusion injuries in multiple organ systems. We hypothesized that treatment with dexmedetomidine would attenuate spinal cord ischemia-reperfusion injury via α-2a receptor activation.MethodsAdult C57BL/6 mice underwent sternotomy, followed by occlusion of the aortic arch for 4 minutes. Eight experimental mice received pretreatment with intraperitoneal dexmedetomidine (25 μg/kg) and at 12-hour intervals after reperfusion. Eight control mice received an equivalent amount of 0.9% normal saline. Five mice underwent the same procedure with dexmedetomidine (25 μg/kg) and atipamezole (250 μg/kg), an α-2a receptor antagonist. Functional analysis of the mice was obtained at 12-hour intervals and scored using the Basso Mouse Scale for Locomotion until 60 hours. All mice were euthanized at 60 hours. Their spinal cords were removed en bloc and were stained with hematoxylin and eosin to assess cytoarchitecture and neuronal viability.ResultsMice treated with the α-2a agonist demonstrated preserved motor function compared with ischemic controls and with mice treated with the α-2a antagonist in addition to the agonist. Functional differences in the dexmedetomidine group were statistically significant from 24 hours through the remainder of the experiment (P < .05). In addition, the treated mice had preserved cytoarchitecture, decreased vacuolization, and improved neuronal viability compared with ischemic control mice and mice concurrently treated with atipamezole, the dexmedetomidine α-2a antagonist.ConclusionsTreatment of mice with the α-2a agonist dexmedetomidine preserves motor function and neuronal viability after aortic cross-clamping. In addition, mice exhibited almost complete reversal of the protective effect with the administration of the α-2a receptor antagonist atipamezole. Dexmedetomidine appears to attenuate spinal cord ischemia-reperfusion injury via α-2a receptor-mediated agonism. Despite surgical adjuncts, paralysis remains a devastating complication after thoracoabdominal aortic interventions. Dexmedetomidine, a selective α-2a agonist commonly used for sedation in the critical care setting, has been shown to have protective effects against ischemia-reperfusion injuries in multiple organ systems. We hypothesized that treatment with dexmedetomidine would attenuate spinal cord ischemia-reperfusion injury via α-2a receptor activation. Adult C57BL/6 mice underwent sternotomy, followed by occlusion of the aortic arch for 4 minutes. Eight experimental mice received pretreatment with intraperitoneal dexmedetomidine (25 μg/kg) and at 12-hour intervals after reperfusion. Eight control mice received an equivalent amount of 0.9% normal saline. Five mice underwent the same procedure with dexmedetomidine (25 μg/kg) and atipamezole (250 μg/kg), an α-2a receptor antagonist. Functional analysis of the mice was obtained at 12-hour intervals and scored using the Basso Mouse Scale for Locomotion until 60 hours. All mice were euthanized at 60 hours. Their spinal cords were removed en bloc and were stained with hematoxylin and eosin to assess cytoarchitecture and neuronal viability. Mice treated with the α-2a agonist demonstrated preserved motor function compared with ischemic controls and with mice treated with the α-2a antagonist in addition to the agonist. Functional differences in the dexmedetomidine group were statistically significant from 24 hours through the remainder of the experiment (P < .05). In addition, the treated mice had preserved cytoarchitecture, decreased vacuolization, and improved neuronal viability compared with ischemic control mice and mice concurrently treated with atipamezole, the dexmedetomidine α-2a antagonist. Treatment of mice with the α-2a agonist dexmedetomidine preserves motor function and neuronal viability after aortic cross-clamping. In addition, mice exhibited almost complete reversal of the protective effect with the administration of the α-2a receptor antagonist atipamezole. Dexmedetomidine appears to attenuate spinal cord ischemia-reperfusion injury via α-2a receptor-mediated agonism.