- Email: [email protected]
Effect of nutritional procurement for the donor liver on Kupffer cell activation in porcine liver transplantation
ELSEVIER
Effect of Nutritional Procurement for the Donor Liver on Kupffer Cell Activation in Porcine Liver Transplantation T. Ishikawa, T. Yagi, N. Ishido, K. Fujisawa, H. Matsuda, A. Endo, Y. Okada, M. Oishi, S. Saito, T. Matsuno, and N. Tanaka
T
HE SIGNIFICANCE of nutritional management of the donor in liver transplantation has not been established. In this study, we investigated the effects of differences in the route of nutritional support of the donor on cold and ischemia-reperfusion injury in the aspects of energy metabolism using a pig liver transplantation model, to clarify the participation of Kupffer cells in these effects.
harvesting, but it was significantly reduced in the FED group at 1 hour after RPF (P < .Ol). In all three groups, C FFA was increased in the early reperfitsion phase (up to 2 hours after RPF). The significant increase of CFFA in the FED group might suggest that energy substrate shifted to FFA in the ischemia-reperfusion damaged graft due to Kupffer cell activation (P < .05, FED vs IVH and GdCl,).
MATERIALS
DISCUSSION
AND
METHODS
Orthotopic liver transplantation was performed using Large-White pigs weighing 20 to 30 kg after 4-hour cold preservation of the graft (4°C Euro-Collins solution). The FED group (n = 5) was fed orally with a standard laboratory diet (1500 kcalid), the IV H group (n = 5) was fasted and given 20% glucose intravenously (50 kcal/kg/d), and the GdCl, group (n = 5) was fed orally with a standard laboratory diet (1500 kcal/d) and intravenously administered GdCl, (10 mg/kg) 24 hours preoperatively. The nutritional pretreatment was applied for 7 days prior to harvesting. The serum aspartate aminotransferase (AST) and hyaluronic acid levels were measured as parameters of hepatocyte and sinusoidal endothelial cell injury, respectively.’ Free fatty acid (FFA) levels in the portal vein and in the hepatic vein were also measured, and serial hepatic FFA clearances (C,,,) were calculated to evaluate liver graft energy substrates.’ Other parameters included glycogen and adenosine triphosphate (ATP) contents of the liver.
Intravenous nutrition of the donor reduced cold and ischemia-reperfusion injury due to sinusoidal endothelial cell injury and, thus, was more graft protective than oral nutrition. Because GdCl, pretreatment inactivating Kupffer cells provided similar graft-protective effects to the IV H group, the differences between the IV H group and FED group are considered to be the difference in the Kupffer cell activity. Hepatic glycogen is the first line of energy substrate under the unphysiologic condition of cold preservation and ischemia-reperfusion.3 In this study, FFA also could be required as an important energy substrate early after RPF, particularly in the FED group. This study showed that hepatic energy substrate varies according to the severity of cold and ischemia-reperfusion injury.
RESULTS
REFERENCES
The mean survival time was significantly longer in the IV H and GdCl, groups than in the FED group (P < .Ol). The serum hyaluronic acid concentration was significantly higher 1 and 2 hours after reperfusion (RPF). The serum hyaluronic acid elimination rate in the FED group was significantly lower at 1 to 2 hours after RPF (P < .OOl). The glycogen granules stored in the hepatocytes were consumed at 1 hour after RPF in all three groups. The ATP content of the graft was not different among these three groups at
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Transplantation
Proceedings,
29, 3357 (1997)
1. Shimizu H, et al: Hepatology 20:1323, 1994 2. Ishikawa T, et al: Transplant Proc 29:397, 1997 3. Sadamori H, et al: Transplantation 60~317, 1995
From the First Department of Surgery, Okayama University Medical School, 2-5-l Shikata-cho, Okayama, 700, Japan. Address reprint requests to Takashi Ishikawa, First Department of Surgery, Okayama University Medical School, 2-5-l Shikata-cho, Okayama, 700, Japan.
0041-1345/97/$17.00 PII SO041 -1345(97)00941-X
3357
Effect of Nutritional Procurement for the Donor Liver on Kupffer Cell Activation in Porcine Liver Transplantation T. Ishikawa, T. Yagi, N. Ishido, K. Fujisawa, H. Matsuda, A. Endo, Y. Okada, M. Oishi, S. Saito, T. Matsuno, and N. Tanaka
T
HE SIGNIFICANCE of nutritional management of the donor in liver transplantation has not been established. In this study, we investigated the effects of differences in the route of nutritional support of the donor on cold and ischemia-reperfusion injury in the aspects of energy metabolism using a pig liver transplantation model, to clarify the participation of Kupffer cells in these effects.
harvesting, but it was significantly reduced in the FED group at 1 hour after RPF (P < .Ol). In all three groups, C FFA was increased in the early reperfitsion phase (up to 2 hours after RPF). The significant increase of CFFA in the FED group might suggest that energy substrate shifted to FFA in the ischemia-reperfusion damaged graft due to Kupffer cell activation (P < .05, FED vs IVH and GdCl,).
MATERIALS
DISCUSSION
AND
METHODS
Orthotopic liver transplantation was performed using Large-White pigs weighing 20 to 30 kg after 4-hour cold preservation of the graft (4°C Euro-Collins solution). The FED group (n = 5) was fed orally with a standard laboratory diet (1500 kcalid), the IV H group (n = 5) was fasted and given 20% glucose intravenously (50 kcal/kg/d), and the GdCl, group (n = 5) was fed orally with a standard laboratory diet (1500 kcal/d) and intravenously administered GdCl, (10 mg/kg) 24 hours preoperatively. The nutritional pretreatment was applied for 7 days prior to harvesting. The serum aspartate aminotransferase (AST) and hyaluronic acid levels were measured as parameters of hepatocyte and sinusoidal endothelial cell injury, respectively.’ Free fatty acid (FFA) levels in the portal vein and in the hepatic vein were also measured, and serial hepatic FFA clearances (C,,,) were calculated to evaluate liver graft energy substrates.’ Other parameters included glycogen and adenosine triphosphate (ATP) contents of the liver.
Intravenous nutrition of the donor reduced cold and ischemia-reperfusion injury due to sinusoidal endothelial cell injury and, thus, was more graft protective than oral nutrition. Because GdCl, pretreatment inactivating Kupffer cells provided similar graft-protective effects to the IV H group, the differences between the IV H group and FED group are considered to be the difference in the Kupffer cell activity. Hepatic glycogen is the first line of energy substrate under the unphysiologic condition of cold preservation and ischemia-reperfusion.3 In this study, FFA also could be required as an important energy substrate early after RPF, particularly in the FED group. This study showed that hepatic energy substrate varies according to the severity of cold and ischemia-reperfusion injury.
RESULTS
REFERENCES
The mean survival time was significantly longer in the IV H and GdCl, groups than in the FED group (P < .Ol). The serum hyaluronic acid concentration was significantly higher 1 and 2 hours after reperfusion (RPF). The serum hyaluronic acid elimination rate in the FED group was significantly lower at 1 to 2 hours after RPF (P < .OOl). The glycogen granules stored in the hepatocytes were consumed at 1 hour after RPF in all three groups. The ATP content of the graft was not different among these three groups at
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Transplantation
Proceedings,
29, 3357 (1997)
1. Shimizu H, et al: Hepatology 20:1323, 1994 2. Ishikawa T, et al: Transplant Proc 29:397, 1997 3. Sadamori H, et al: Transplantation 60~317, 1995
From the First Department of Surgery, Okayama University Medical School, 2-5-l Shikata-cho, Okayama, 700, Japan. Address reprint requests to Takashi Ishikawa, First Department of Surgery, Okayama University Medical School, 2-5-l Shikata-cho, Okayama, 700, Japan.
0041-1345/97/$17.00 PII SO041 -1345(97)00941-X
3357