Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model

Marubashi, Shigeru; Sakon, Masato; Nagano, Hiroaki; Gotoh, Kunihito; Hashimoto, Kazuhiko; Kubota, Masaru; Kobayashi, Shogo; Yamamoto, Shinji; Miyamoto, Atsushi; Dono, Keizo; Nakamori, Shoji; Umeshita, Koji; Monden, Morito

doi:10.1016/j.surg.2004.03.012

Cited by 77 publications

(56 citation statements)

References 39 publications

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“…The hepatic capillaries have fenestrated endothelial cells which bring direct access of plasma through the endothelial cells to the hepatocytes. A recent study demonstrated that if these changes are prevented by keeping pressure of the portal vein constant, there is deficient activation of HGF and increased hepatocyte apoptosis, even though the kinetics of PCNA nuclear labeling do not seem to be affected (Marubashi et al, 2004). Another point that needs to be better understood is the potential impact of the change of oxygen partial pressure in the hepatic blood after PHx.…”

Section: Hemodynamic Changes Following 2/3 Partial Hepatectomymentioning

confidence: 99%

Liver regeneration

Michalopoulos

2007

Journal Cellular Physiology

1,317

1,224

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Liver regeneration after partial hepatectomy is a very complex and well-orchestrated phenomenon. It is carried out by the participation of all mature liver cell types. The process is associated with signaling cascades involving growth factors, cytokines, matrix remodeling, and several feedbacks of stimulation and inhibition of growth related signals. Liver manages to restore any lost mass and adjust its size to that of the organism, while at the same time providing full support for body homeostasis during the entire regenerative process. In situations when hepatocytes or biliary cells are blocked from regeneration, these cell types can function as facultative stem cells for each other.

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Section: Hemodynamic Changes Following 2/3 Partial Hepatectomymentioning

confidence: 99%

Liver regeneration

Michalopoulos

2007

Journal Cellular Physiology

1,317

1,224

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“…The mechanism of this effect is unclear, but some insight can be gained from the comparison of different recipient groups: cirrhotic patients receiving a partial graft show faster regeneration than noncirrhotics, which could be due to a higher portal flow (16), higher portal pressure (17) or a more proproliferogenic environment in patients with chronic hepatic insufficiency. The inter-dependence of portal flow and regeneration is illustrated by impaired regeneration after portosystemic shunting in rats (18).…”

Section: Graft-related Factorsmentioning

confidence: 99%

“…We would speculate that a beneficial effect of portal venous inflow reduction stems from the increase in arterial flow. However, it is important to bear in mind that portal flow can only be reduced to a certain degree, as regeneration is also dependent on portal flow (18).…”

Section: Vascular Inflowmentioning

confidence: 99%

Small‐for‐Size Syndrome After Partial Liver Transplantation: Definition, Mechanisms of Disease and Clinical Implications

Dahm

Georgiev

Clavien

2005

American Journal of Transplantation

552

498

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Widespread application of cadaveric split or living donor liver transplantation bears considerable potential to increase the pool of available organs and thus alleviate the problem of organ shortage. Although splitting of a cadaveric liver into two grafts for adult recipients can be performed successfully, sufficient function of undersized grafts is a major concern. To minimize the risk for living donors, transplant surgeons aim at procuring the least necessary liver volume, also leading to potentially small grafts. When small partial grafts are unable to meet the functional demands, the recipients can develop a so-called smallfor-size syndrome (SFSS). There is currently limited data on the pathogenesis of SFSS, with clinical studies mainly focusing on portal hyperperfusion. Additional aspects include graft-related factors such as functional and regenerative capacity, as well as recipient-related factors, such as overall health status and severity of cirrhosis. However, there is currently no consensus on the definition of SFSS. We propose a novel definition, based on simple clinical criteria, which divides the syndrome into either nonfunction or dysfunction of a small graft after the exclusion of other causes. This definition should ease comparability of future clinical trials, and thus improve understanding of the pathogenesis of SFSS.

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“…Although the difference of HTBF caused by partial ligation of the portal vein may have lasted only for a short period after the operation, the initial HTBF affected liver regeneration and functions associated with gene expression. Recently, Marubashi et al [21] developed a novel model to investigate the effect of portal blood flow on liver regeneration. They also found that liver generation was attenuated in the low portal pressure model, although the pressure difference did not last for more than 12 h. The early events they reported are consistent with our results.…”

Section: Surgical Model To Investigate the Htbfmentioning

confidence: 99%

Portal Blood Flow Regulates Volume Recovery of the Rat Liver after Partial Hepatectomy: Molecular Evaluation

et al. 2006

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Background/Aim: Liver regeneration is a finely tuned process that is closely regulated by multiple cell cycle steps. Although the portal blood flow affects liver regeneration, the molecular mechanism by which the blood flow regulates gene expression and liver function is largely unknown. The aim of this study was to investigate the molecular effect of portal blood flow on hepatocyte proliferation and gene regulation during liver regeneration. Materials and Methods: We developed a simple surgical rat model to investigate the relation between portal blood flow and liver regeneration by partially ligating the portal trunk with 8-0 Proline sutures under microscopy to reduce the blood flow by 40%. We investigated recovery of liver volume, DNA synthesis, and gene expression associated with cell cycle regulators, comparing partially hepatectomized (PH) rats without (PH group; n = 30) and with partial portal ligation (PHPL group; n = 30) for 7 days after the operation. Results: The hepatic tissue blood flow and the recovery ratio between liver weight and body weight in the PHPL group were significantly lower than in the PH group after hepatectomy. The peak 5-bromo-2′-deoxyuridine labeling index in the PHPL group was delayed and weak compared with the PH group. The expression of CT-1 and cyclin D, E, and B mRNAs indicated that the liver regeneration in the PHPL group was delayed and weak. In addition, there was reciprocal expression of C/EBPα and C/EBPβ mRNAs, an observation supported by their nuclear protein levels. Furthermore, the cytochrome P-450 protein level in the PHPL group was higher than that in the PH group 1 day after hepatectomy. Conclusion: The portal blood flow regulates the activity of liver regeneration and the gene expression associated with cell cycle regulators, while the functions are maintained.

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Effect of portal hemodynamics on liver regeneration studied in a novel portohepatic shunt rat model

Cited by 77 publications

References 39 publications

Liver regeneration

Liver regeneration

Small‐for‐Size Syndrome After Partial Liver Transplantation: Definition, Mechanisms of Disease and Clinical Implications

Portal Blood Flow Regulates Volume Recovery of the Rat Liver after Partial Hepatectomy: Molecular Evaluation

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