L. S. Foley1, J. Mares1, F. Puskas1, M. T. Bell1, D. T. Bennett1, K. Freeman1, M. Weyant1, D. A. Fullerton1, T. B. Reece1 1University Of Colorado Denver,Surgery/Cardiothoracic,Aurora, CO, USA
Introduction: Delayed paraplegia is a devastating complication of thoracoabdominal aortic surgery. Erythropoietin (EPO) attenuates this injury in models of spinal cord ischemia. Proposed mechanisms include induction of ischemic tolerance in normal tissue and activation of an ischemia-induced receptor, which attenuates neuronal loss in ischemic tissue. This study aims to elucidate mechanisms of EPO-mediated neuroprotection. We hypothesized that EPO acts on ischemic tissue to limit neuronal loss.
Methods: Adult male C57/BL6 mice underwent sternotomy and 4-minute thoracic aortic crossclamp. Seven pretreatment mice received EPO (20U/kg) via intraperitoneal injection 24 hours prior to operation. Seven perioperative mice received the same EPO dose 4 hours prior to operation. Seven controls received 0.9% saline. Four sham mice underwent saline administration and sternotomy without crossclamp. Functional outcomes were measured using Basso motor score for 48 hours (Basso score ranges 1-9; 1 refers to complete paralysis and 9 is normal hind-limb motor function). Spinal cords were harvested and homogenized for biochemical analysis.
Results: Ischemia reperfusion (IR) injury uniformly induced paraplegia in control mice (p<0.01). Synchronous EPO administration with IR prevented motor decline, which occurred in ischemic controls and EPO pretreated mice starting at 36 hours post-op (mean Basso 6.43 vs 1.86 and 3, respectively; p<0.01). All ischemic control and pretreatment mice progressed to paraplegia, with no significant difference in hind limb function at all time points.
Conclusion: EPO administration attenuates functional decline following spinal cord ischemia reperfusion injury when administered concomitant to the injury, but this effect is lost when EPO is given as a pretreatment. These findings point towards a potential salvaging role for EPO following neurologic injury. Elucidation of mechanisms involved in spinal cord protection is essential for reducing delayed paraplegia.