M. A. Baker1, P. Nandivada1, A. Pan1, G. L. Fell1, L. Anez-Bustillos1, D. T. Dao1, K. M. Gura2, V. Nosé3, M. Puder1 1Boston Children’s Hospital,Vascular Biology Program And Department Of Surgery,Boston, MA, USA 2Boston Children’s Hospital,Department Of Pharmacy,Boston, MA, USA 3Massachusetts General Hospital,Department Of Pathology,Boston, MA, USA
Introduction: Ischemia reperfusion injury (IRI) is a major barrier to liver surgery and transplantation, particularly with steatotic livers. Fish oil lipid emulsions are rich in anti-inflammatory omega-3 fatty acids and the antioxidant alpha-tocopherol. The purpose of this study was to determine if pre-treatment with a single dose of intravenous fish oil (IVFO) can decrease hepatic IRI.
Methods: Male 6-8 wk old C57BL/6 mice received 1 g/kg IVFO (Omegaven®, Fresenius Kabi) or isovolumetric saline via tail vein injection 1 h prior to suture ligature of the portal triad to the cephalad liver lobes. After 30 min of 70% hepatic ischemia, livers were reperfused. Animals were sacrificed after 4, 8, or 24 h of reperfusion and livers harvested for histologic analysis by a single, blinded, board-certified pathologist. Percent necrosis was calculated using ImageJ software (NIH).
Results: After 4 h of reperfusion, saline-treated livers demonstrated marked ischemia around central veins diffusely, while IVFO-treated livers demonstrated small, scattered foci of necrosis with normal liver between necrotic areas. After 8 h of reperfusion, both saline and IVFO-treated livers demonstrated pale areas of cell loss with surrounding regenerating hepatocytes. There were more regenerating cells around areas of necrosis in IVFO-treated livers, which was confirmed with Ki67 staining and may represent faster recovery. After 24 h of reperfusion, both saline and IVFO-treated livers demonstrated patchy areas of frank necrosis and normal appearing liver, without preference for central vein or portal space, with a decreased overall percent area of necrosis in IVFO-treated livers (saline mean 9.27 ± SEM 2.50 %, n=7 vs. IVFO mean 1.70 ± SEM 0.44 %, n=9; P=0.03). Figure 1 demonstrates representative H&E images of livers after IRI at 200x magnification (open arrows = ischemia, closed arrows = necrosis).
Conclusion: Temporal findings after hepatic IRI suggest IVFO’s hepatoprotective effects may be related to accelerating healing. Specific fatty acid receptor knockout studies are underway to determine the mechanism of this protection.
