Abstract
Background. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). This study was designed to evaluate the effects of a preconditioning oral nutritional supplement (pONS) containing glutamine, antioxidants, and green tea extract on hepatic warm IRI in pigs. Methods. pONS (70 g per serving, Fresenius Kabi, Germany) was dissolved in 250 mL tap water and given to pigs 24, 12, and 2 hrs before warm ischemia of the liver. A fourth dose was given 3 hrs after reperfusion. Controls were given the same amount of cellulose with the same volume of water. Two hours after the third dose of pONS, both the portal vein and the hepatic artery were clamped for 40 min. 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Liver tissue was taken 8 hrs after reperfusion for histology and immunohistochemistry. Results. HR, MAP, CVP, HAF, and PVF were comparable between the two groups. pONS significantly increased bile flow 8 hrs after reperfusion. ALT and AST were significantly lower after pONS. Histology showed significantly more severe necrosis and neutrophil infiltration in controls. pONS significantly decreased the index of immunohistochemical expression for TNF-α, MPO, and cleaved caspase-3 (P < 0.001). Conclusion. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis.
Highlights
During liver surgery, the inflow occlusion maneuver to prevent blood loss as well as the liver manipulation itself have been shown to induce a cascade of molecular events, referred to as ischemia-reperfusion injury (IRI)
Continuous postperfusion monitoring of the hemodynamic parameters (HR, mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF)) showed no significant differences between the two groups (Table 2)
While serum ALT increased in controls after warm ischemia/reperfusion to the liver, preconditioning oral nutritional supplement (pONS) prevented this effect; the difference between the two groups started to be significant 6 hours after reperfusion (49 ± 3 U/L in controls versus 35 ± 3 U/L in pONS; P = 0.01)
Summary
The inflow occlusion maneuver to prevent blood loss as well as the liver manipulation itself have been shown to induce a cascade of molecular events, referred to as ischemia-reperfusion injury (IRI). During IRI, intestinal endotoxins (LPS) leak through the altered gut membrane into the portal circulation and enhance the phagocytosis in hepatic KCs [28,29,30,31,32,33,34,35]. To. Several approaches have been proposed to pharmacologically ameliorate hepatic ischemia/reperfusion injury (IRI). 0.5, 3, 6, and 8 hrs after reperfusion, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), portal venous flow (PVF), hepatic arterial flow (HAF), bile flow, and transaminases were measured. Administration of pONS before and after tissue damage protects the liver from warm IRI via mechanisms including decreasing oxidative stress, lipid peroxidation, apoptosis, and necrosis
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