Abstract 17308: Pharmacological Induction of Beta Common Receptor Amplifies Erythropoietin Attenuation of Spinal Cord Injury
Introduction: Paraplegia remains the most feared complication of thoracoabdominal aorticintervention. While erythropoietin (EPO) has demonstrated neuroprotective effects in spinal cord ischemia, EPO does not work until the Beta Common Receptor (bcR) is induced by ischemia. We hypothesized that BCR could be pharmacologically with Diazoxide (DZ) induced prior to ischemia with amplification of the neuroprotective effects from spinal cord ischemia.
Methods: For DZ time trial, adult male C57/BL6 received DZ (40 mg/kg) by oral gavage. After 0, 12, 24, 36 and 48 hours of administration, spinal cords were harvested. For optimal dosing, DZ (0, 5, 10, 20, 40 mg/kg) was administered. The expression of bcR was assesed by western blot analysis. Four groups were studied: PBS (pretreatment)+PBS (immediately before), PBS+EPO, DZ+PBS, and DZ+EPO. Spinal cord ischemia was induced by 4-minutes thoracic aortic cross-clamp. Functional scoring (Basso Mouse Score) was done 12-hour intervals.
Results: Optimal bcR upregulation occurred 36 hours after administration of DZ (Figure 1). The optimal dosage for bcR induction was 40 mg/kg of DZ. The motor function of DZ+EPO (6.7±1.0) was significantly preserved compared to all other groups (Figure2), while the DZ and EPO groups in isolation were significantly better than ischemia controls.
Conclusions: Pharmacological upregulation of bcR is feasible with resultant improved efficacy of EPO in preventing spinal cord injury. Better understanding of this two stage protective mechanism of EPO may serve to further prevent ischemic complications for high risk aortic intervention.
Author Disclosures: K. Yamanaka: None. M. Aftab: None. M.T. Bell: None. L.S. Foley: None. J. Mares: None. D.A. Fullerton: None. B.T. Reece: None.
- © 2016 by American Heart Association, Inc.