Meredith A Baker1, Prathima Nandivada1, Paul D Mitchell2, Gillian L Fell1, Amy Pan1, Lorenzo Anez-Bustillos1, Duy T Dao1, Kathleen M Gura3, Vania Nosé4, Mark Puder5. 1. Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. 2. Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, USA. 3. Department of Pharmacy, Boston Children's Hospital, Boston, MA, USA. 4. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. 5. Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, MA, USA. Electronic address: mark.puder@childrens.harvard.edu.
Abstract
BACKGROUND: Ischemia reperfusion injury is a barrier to liver surgery and transplantation, particularly for steatotic livers. The purpose of this study was to determine if pretreatment with a single dose of intravenous fish oil decreases hepatic ischemia reperfusion injury and improves recovery of injured livers. METHODS: Sixty adult male C57BL/6 mice received 1 g/kg intravenous fish oil (Omegaven, Fresenius Kabi) or isovolumetric 0.9% NaCl (saline) via tail vein 1 hour before 30 minutes of 70% hepatic ischemia. Animals were killed 4, 8, or 24 hours postreperfusion, and livers were harvested for histologic analysis. RESULTS: Four hours postreperfusion, saline-treated livers demonstrated marked ischemia diffusely around the central veins, while intravenous fish oil-treated livers demonstrated only patchy necrosis with intervening normal parenchyma. Eight hours postreperfusion, all livers demonstrated pale areas of cell loss with surrounding regenerating hepatocytes. Ki67 staining confirmed 14.4/10 high-powered field (95% confidence interval, 3.2-25.6) more regenerating hepatocytes around areas of necrosis in intravenous fish oil-treated livers. Twenty-four hours postreperfusion, all livers demonstrated patchy areas of necrosis, with an 89% (95% confidence interval, 85-92) decrease in the area of necrosis in intravenous fish oil-treated livers. CONCLUSION: Intravenous fish oil treatment prior to hepatic ischemia reperfusion injury decreased the area of hepatic necrosis and increased hepatocyte regeneration compared to saline treatment in a mouse model.
BACKGROUND:Ischemia reperfusion injury is a barrier to liver surgery and transplantation, particularly for steatotic livers. The purpose of this study was to determine if pretreatment with a single dose of intravenous fish oil decreases hepatic ischemia reperfusion injury and improves recovery of injured livers. METHODS: Sixty adult male C57BL/6 mice received 1 g/kg intravenous fish oil (Omegaven, Fresenius Kabi) or isovolumetric 0.9% NaCl (saline) via tail vein 1 hour before 30 minutes of 70% hepatic ischemia. Animals were killed 4, 8, or 24 hours postreperfusion, and livers were harvested for histologic analysis. RESULTS: Four hours postreperfusion, saline-treated livers demonstrated marked ischemia diffusely around the central veins, while intravenous fish oil-treated livers demonstrated only patchy necrosis with intervening normal parenchyma. Eight hours postreperfusion, all livers demonstrated pale areas of cell loss with surrounding regenerating hepatocytes. Ki67 staining confirmed 14.4/10 high-powered field (95% confidence interval, 3.2-25.6) more regenerating hepatocytes around areas of necrosis in intravenous fish oil-treated livers. Twenty-four hours postreperfusion, all livers demonstrated patchy areas of necrosis, with an 89% (95% confidence interval, 85-92) decrease in the area of necrosis in intravenous fish oil-treated livers. CONCLUSION: Intravenous fish oil treatment prior to hepatic ischemia reperfusion injury decreased the area of hepatic necrosis and increased hepatocyte regeneration compared to saline treatment in a mouse model.
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