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57th Annual Meeting Abstracts


Poster 1

Abstract Title

Ethyl Pyruvate Prevents Delayed Paralysis In a Murine Model of Spinal Cord Ischemic Injury

 

Author Block

Bao-Ngoc H Nguyen, MD, Hassan Albadawi, MD, Robert S. Crawford, MD, Hyung-Jin Yoo, MD, Mark Conrad, MD, Richard P. Cambria, MD, Michael T. Watkins, MD

Massachusetts General Hospital, Harvard University,Boston, MA

 

Abstract Body

Background: Delayed paraplegia(DP)is a problem for patients undergoing complex repair of the thoracoabdominal aorta. These experiments were designed to determine whether Ethyl Pyruvate (EP), a potent anti-inflammatory agent and antioxidant known to provide protection against shock, sepsis and ischemia reperfusion injury, might ameliorate DP.

Methods: Two groups of C57BL6 mice were subjected to 5 minutes of thoracic aortic ischemia followed by reperfusion for up to 48hrs (TAR). Mice received either 300mg/kg EP (n=12) or lactated ringers (LR, n=10) at 30min before ischemia and 3 hrs after reperfusion. Neurologic function was assessed using an established rodent scale. Spinal cord tissue was analyzed for markers of inflammation (KC, IL-6: ELISA), anti-apoptosis (BcL-2, immunoblotting). Nissl bodies stained motor neurons were counted in the anterior horns sections from L1-L5 segments (cells/section). Statistical analysis utilized t test and χ2.

Results: All mice manifested mild transient paraplegia immediately after surgery which completely resolved within one hour. All mice manifested mild transient paraplegia immediately after surgery which completely resolved within one hour. All LR mice developed dense DP between 40-48hrs reperfusion. In contrast 80% of EP mice had no DP (p<0.005). The number of motor neurons were significantly higher in the EP treated mice compared to LR (296 vs. 184 cells p=0.04). BcL-2 expression was higher in the EP treated animals at 24hrs reperfusion (37049 vs. 32.361.0 arbitrary units, p<0.01). There was a significantly lower expression of KC and IL-6 at 48 hours reperfusion in the EP group (KC: 20.8 vs. 163 pg/mg protein, p<0.01), (IL-6: 1.40.3 vs.329 pg/mg protein, p<0.001).

Conclusion: The protection provided by EP against DP correlated with preservation of motor neurons, higher anti-apoptotic molecule and decreased spinal cord inflammation. EP may be a promising treatment for humans at risk for delayed paralysis following graft replacement of the thoracoabdominal aorta.

 

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