Abstract:Background: Portal flow diversion by portacaval shunts (PCS) has been shown to prevent primary graft nonfunction in liver transplantation using small-for-size grafts. In this study, we examine whether PCS can improve reperfusion injury after major hepatectomy in pigs. Materials and Methods: In 14 pigs, a partial PCS was constructed following 65% hepatectomy and 1 h of inflow ischemia. During 24 h of reperfusion, the shunt was either closed (group A, n = 7) or left open (group B, n = 7). Results: 24 h after rep… Show more
“…Hematoxylin-eosin (H & E) staining demonstrated mixed small and large hepatocyte nuclei, and accumulations of fatty globules in hepatocytes following PH; this anisokaryosis and simultaneous fatty degeneration indicates both regenerative and degenerative changes in the hepatocytes 25 , 26 . These effects were detected 10 and 17 days after PH in RS-treated animals, while they were already present after only 3 days in controls (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…5c–e ). To gain further insights into the regenerative response in pigs exposed to RS, we next quantified the proliferating cell nuclear antigen (PCNA) and Ki-67 expression 25 , 27 , 28 . The number of PCNA-positive cells was significantly higher in RS-treated animals than controls at PH.…”
Section: Resultsmentioning
confidence: 99%
“…Histological findings also demonstrated that the regenerative responses of RS-treated animals were suppressed 3 days after PH. Although it is difficult to distinguish regenerative reactions from degenerative changes of liver tissues morphologically (because these changes are frequently seen simultaneously), the presence of anisokaryosis and binucleated hepatocytes suggested regenerative responses as well as the expected fatty degeneration 25 , 26 . Immunohistochemistry data supported the hypothesis that RS-treatment suppressed the cell cycle and delayed liver regeneration.…”
A feasible large animal model to evaluate regenerative medicine techniques is vital for developing clinical applications. One such appropriate model could be to use retrorsine (RS) together with partial hepatectomy (PH). Here, we have developed the first porcine model using RS and PH. RS or saline control was administered intraperitoneally to Göttingen miniature pigs twice, two weeks apart. Four weeks after the second dose, animals underwent PH. Initially, we tested different doses of RS and resection of different amounts of liver, and selected 50 mg/kg RS with 60% hepatectomy as our model for further testing. Treated animals were sacrificed 3, 10, 17 or 28 days after PH. Blood samples and resected liver were collected. Serum and liver RS content was determined by Liquid Chromatograph-tandem Mass Spectrometer. Blood analyses demonstrated liver dysfunction after PH. Liver regeneration was significantly inhibited 10 and 17 days after PH in RS-treated animals, to the extent of 20%. Histological examination indicated hepatic injury and regenerative responses after PH. Immunohistochemical staining demonstrated accumulation of Cyclin D1 and suppression of Ki-67 and PCNA in RS-treated animals. We report the development of the first large animal model of sustained liver injury with suppression of hepatic regeneration.
“…Hematoxylin-eosin (H & E) staining demonstrated mixed small and large hepatocyte nuclei, and accumulations of fatty globules in hepatocytes following PH; this anisokaryosis and simultaneous fatty degeneration indicates both regenerative and degenerative changes in the hepatocytes 25 , 26 . These effects were detected 10 and 17 days after PH in RS-treated animals, while they were already present after only 3 days in controls (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…5c–e ). To gain further insights into the regenerative response in pigs exposed to RS, we next quantified the proliferating cell nuclear antigen (PCNA) and Ki-67 expression 25 , 27 , 28 . The number of PCNA-positive cells was significantly higher in RS-treated animals than controls at PH.…”
Section: Resultsmentioning
confidence: 99%
“…Histological findings also demonstrated that the regenerative responses of RS-treated animals were suppressed 3 days after PH. Although it is difficult to distinguish regenerative reactions from degenerative changes of liver tissues morphologically (because these changes are frequently seen simultaneously), the presence of anisokaryosis and binucleated hepatocytes suggested regenerative responses as well as the expected fatty degeneration 25 , 26 . Immunohistochemistry data supported the hypothesis that RS-treatment suppressed the cell cycle and delayed liver regeneration.…”
A feasible large animal model to evaluate regenerative medicine techniques is vital for developing clinical applications. One such appropriate model could be to use retrorsine (RS) together with partial hepatectomy (PH). Here, we have developed the first porcine model using RS and PH. RS or saline control was administered intraperitoneally to Göttingen miniature pigs twice, two weeks apart. Four weeks after the second dose, animals underwent PH. Initially, we tested different doses of RS and resection of different amounts of liver, and selected 50 mg/kg RS with 60% hepatectomy as our model for further testing. Treated animals were sacrificed 3, 10, 17 or 28 days after PH. Blood samples and resected liver were collected. Serum and liver RS content was determined by Liquid Chromatograph-tandem Mass Spectrometer. Blood analyses demonstrated liver dysfunction after PH. Liver regeneration was significantly inhibited 10 and 17 days after PH in RS-treated animals, to the extent of 20%. Histological examination indicated hepatic injury and regenerative responses after PH. Immunohistochemical staining demonstrated accumulation of Cyclin D1 and suppression of Ki-67 and PCNA in RS-treated animals. We report the development of the first large animal model of sustained liver injury with suppression of hepatic regeneration.
“…Similarly, it has been suggested that after extensive hepatectomies, a small liver remnant is vulnerable to functional impairment, probably induced by the enforced diversion of the entire portal flow through a restricted sinusoidal network and the resulting shear stress and congestion of the sinusoidal endothelial lining cells [12][13][14].…”
Liver remnants less than 30% of standard liver weight are much more susceptible to ischemia/reperfusion injury than controls twice the size. Adjustment of serum markers of hepatocyte injury to the liver remnant weight depicts injury more accurately.
Porcine models of extended hepatectomy and liver transplantation (LT) of reduced graft have been widely used for studying the small-for-size (SFS) syndrome and the various modalities of portal inflow modulation (PIM). However, considerable heterogeneity exists among the studies and their results. The aim of this review was to assess the main advantages and drawbacks of the different porcine models of SFS LT and SFS hepatectomy, and propose a standardized anatomical nomenclature for the various models. The MEDLINE database was searched for articles reporting porcine models of reduced graft LT or hepatectomy of more than 65%. Nineteen articles on SFS LT matched our inclusion criteria, including 10 articles reporting a model of PIM. Twenty-seven articles reporting a model of posthepatectomy SFS were identified, of which 16 reported a model of PIM. Subtotal hepatectomy (i.e. resection of all segments except segment 1) without inflow occlusion, left trisectionectomy with inflow occlusion, and LT of a right lateral section including the caudate lobe in a larger recipient appeared to be the most suitable porcine models for studying the SFS syndrome. All three models were appropriate for assessing the surgical and pharmaceutical PIM modalities, except for those involving the splenic flow.
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