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Dexmedetomidine, an α-2a adrenergic agonist, promotes ischemic tolerance in a murine model of spinal cord ischemia-reperfusion  Marshall T. Bell, MD,

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Presentation on theme: "Dexmedetomidine, an α-2a adrenergic agonist, promotes ischemic tolerance in a murine model of spinal cord ischemia-reperfusion  Marshall T. Bell, MD,"— Presentation transcript:

1 Dexmedetomidine, an α-2a adrenergic agonist, promotes ischemic tolerance in a murine model of spinal cord ischemia-reperfusion  Marshall T. Bell, MD, Ferenc Puskas, MD, PhD, Daine T. Bennett, MD, Paco S. Herson, PhD, Nidia Quillinan, PhD, David A. Fullerton, MD, T. Brett Reece, MD  The Journal of Thoracic and Cardiovascular Surgery  Volume 147, Issue 1, Pages (January 2014) DOI: /j.jtcvs Copyright © Terms and Conditions

2 Figure 1 Graphic representation of the study design. AKT, Protein kinase B; CREB, cyclic AMP response-element binding protein; BCL2, B-cell lymphoma 2; BDNF, brain-derived neurotrophic factor; Dex, dexmedetomidine. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

3 Figure 2 Following ischemia-reperfusion (IR) surgery with 5 minutes of aortic occlusion a significant functional deficit in hind-limb function was observed in all mice. Twenty-four hours of pretreatment with dexmedetomidine (IR+Dex) resulted in significantly higher neurologic function at all time points postoperatively. Error bars represent standard error of the mean. ∗P < .05. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

4 Figure 3 Mice undergoing ischemia-reperfusion surgery had a significant disruption of cytoarchitecture when compared with sham mice. A reduction of normal-appearing anterior horn neurons and increased vacuolization was observed in ischemic control mice (IR) when compared with the sham and treatment (IR+DEX) groups. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

5 Figure 4 All mice undergoing ischemia-reperfusion surgery had a significant increase in Flouro Jade–B (EDM Millipore, Billerica, Mass)-positive neurons. Mice treated with dexmedetomidine (IR+DEX) had a significant reduction in neuronal injury when compared with ischemic controls (IR). Error bars represent standard error of the mean. *P < P < .0001. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

6 Figure 5 Spinal cord cellular signaling of neuroprotective pathways at time point 0. Mice receiving pretreatment alone with dexmedetomidine (Dex) had significantly higher phosphorylation of prosurvival protein kinase (pAKT) (P = .005) and prosurvival cyclic AMP response-element binding protein (pCREB) (P = .004) in all patients P values of <0.05 are denoted by “*” when compared with mice receiving normal saline (NS) 0.9%. *P < .05. Error bars represent standard error of the mean. tAKT, Total protein kinase B; tCREB, total cyclic amp response element binding protein. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

7 Figure 6 A, Quantitative polymerase chain reaction for production of B-cell lymphoma 2 (BCL-2) and brain-derived neurotrophic factor (BDNF) transcripts was performed. Pretreatment with dexmedetomidine resulted in a significant up-regulation of BCL-2 (P ≤ .0001) and BNDF (P = .040) messenger RNA expression at time point 0. B, Expression of cyclic AMP response-element binding-mediated neuroprotective proteins BCL-2 and BDNF was examined 48 hours following ischemia-reperfusion (IR) surgery and compared with housekeeping protein β-actin. Significant elevations in both BCL-2 (P = .004) and BDNF (P = .0035) expression following IR surgery were observed with dexmedetomidine pretreatment (IR+Dex) when compared with ischemic controls (IR) 48 hours following surgery. C, Representative immunoblot following IR. Error bars represent standard error of the mean. DDCT, Expression. The Journal of Thoracic and Cardiovascular Surgery  , DOI: ( /j.jtcvs ) Copyright © Terms and Conditions

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