The compensatory hyperplasia (liver regeneration) following ligation of a portal branch is initiated before the atrophy of the deprived lobes

Lambotte, Luc; Li, Bo; Leclercq, Isabelle; Sempoux, Christine; Saliez, Alain; Horsmans, Yves

doi:10.1016/s0168-8278(00)80098-7

Cited by 32 publications

(15 citation statements)

References 17 publications

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“…Retrorsine was dissolved in HCl (pH 2.5) followed by neutralization by NaOH 0.1 N, as described. 14,15 At 4 weeks after the second injection, PBL was performed as described 3 and four to eight animals per group were killed at 0, 30 min, 3,5,12,24,48,72 and 168 h after PBL. Livers were excised and samples of anterior and posterior lobes were immersed in 4% buffered formaldehyde for histological and immunohistochemical analysis.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

“…1 Liver regeneration of the proliferating lobes after PBL has been extensively studied and has been shown to be similar to that observed after partial hepatectomy. [2][3][4] In contrast, the precise events resulting in the atrophy of the ligated lobes have not been described yet. This is rather surprising, as apoptosis, first called shrinkage necrosis, was actually first described by Kerr in this model.…”

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confidence: 99%

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Molecular mechanisms of apoptosis in the liver of rats after portal branch ligation with and without retrorsine

Picard

Stärkel

Sempoux³

et al. 2004

Laboratory Investigation

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The mechanisms accounting for the atrophy of the portal blood-deprived liver lobes after portal branch ligation (PBL) are still unclear. The first aim of this study was to confirm the role of apoptosis in this process and to determine which apoptotic pathways are involved. The second aim of the study was to evaluate the effect of blocking compensatory hyperplasia of the nonligated lobes with retrorsine on the mechanisms of apoptosis in the ligated lobes. Mitochondrial Bax, Bcl-2 and Bcl-X L , cytosolic cytochrome c, caspase-3, -8 and -9 activities and TNF-a levels were assessed in the liver of rats before and at various time points, ranging from 30 min to 7 days, after PBL. Caspase activities were also measured in rats pretreated with retrorsine. Both the mitochondrial and the death receptor-mediated pathways are activated in the ligated liver lobes after portal branch ligation. Caspase activation is inhibited by retrorsine pretreatment, resulting in fewer apoptotic bodies. Apoptosis accounts for the atrophy of the ligated lobes after PBL. It is inhibited by retrorsine, suggesting an attempt to reduce the loss of liver mass when hyperplasia of the nonligated lobes is impaired.

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Section: Animals and Experimental Designmentioning

confidence: 99%

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confidence: 99%

Molecular mechanisms of apoptosis in the liver of rats after portal branch ligation with and without retrorsine

Picard

Stärkel

Sempoux³

et al. 2004

Laboratory Investigation

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“…However, little is known about whether the portal branch ligation (PBL)-induced atrophy of the tumor-bearing lobe affects nutritional blood supply and thus tumor growth. In contrast to the compensatory hypertrophy, which is initiated directly by an early proliferative response (9), the rapid shrinkage of the ligated lobe is thought to be associated with a reduction in size and number of hepatocytes, most probably due to sustained hypoxia and metabolic deprivation of portal hepatotrophic factors (15,20,34). The PBL-induced atrophy involves both centrolobular necrosis and apoptotic cell death in a timedependent manner, however, without affecting the hepatic microarchitecture (15,16,20,25,29).…”

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confidence: 99%

Portal branch ligation induces a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and cell proliferation in portal blood-deprived liver tissue

Kollmar

Corsten²,

Scheuer³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Portal branch ligation (PBL) may prevent liver failure after extended hepatic resection. However, clinical studies indicate that tumors within the ligated lobe develop accelerated growth. Although it is well known that tumor growth depends on the host's microvascularization, there is no information about how PBL affects the hepatic microcirculation. Our aims were to determine hepatic artery response, liver microcirculation, tissue oxygenation, and cell proliferation after PBL. Therefore, we used intravital multifluorescence microscopy, laser-Doppler flowmetry, immunohistochemistry, and biochemical techniques to examine microcirculatory responses, microvascular remodeling, and cellular consequences after left lateral PBL in BALB/c mice. During the first 7 days, PBL induced a reduction of left hilar blood flow by ∼50%. This resulted in 80% sinusoidal perfusion failure, significant parenchymal hypoxia, and liver atrophy. After 14 days, however, left hilar blood flow was found to be restored. However, remodeling of the microvasculature included a rarefaction of the sinusoidal network, however, without substantial perfusion failure, compensated by a hepatic arterial buffer response and significant sinusoidal dilatation. This resulted in normalization of tissue oxygenation, indicating arterialization of the ligated lobe. Interestingly, late microvascular remodeling was associated with increased endothelial nitric oxide synthase expression, significant hepatocellular proliferation, and weight gain of the ligated lobe. Thus PBL induces only an initial microcirculatory failure with liver atrophy, followed by a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and hepatocellular proliferation. This may explain the accelerated tumor progression occasionally observed in patients after PBL.

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“…The effect of portal vein occlusion is well known. The ligation of a portal branch induces atrophy of the portally ligated liver lobe(s), while the portally supplied liver lobes undergo compensatory growth [59,60,61]. This finding is of great clinical relevance and was translated into a surgical therapeutic concept: portal vein occlusion as a strategy to enlarge the future liver remnant prior to extended liver resection.…”

Section: Surgical Modelsmentioning

confidence: 99%

Rodent Models and Imaging Techniques to Study Liver Regeneration

Wei

Dirsch²,

McLean³

et al. 2014

Eur Surg Res

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The liver has the unique capability of regeneration from various injuries. Different animal models and in vitro methods are used for studying the processes and mechanisms of liver regeneration. Animal models were established either by administration of hepatotoxic chemicals or by surgical approach. The administration of hepatotoxic chemicals results in the death of liver cells and in subsequent hepatic regeneration and tissue repair. Surgery includes partial hepatectomy and portal vein occlusion or diversion: hepatectomy leads to compensatory regeneration of the remnant liver lobe, whereas portal vein occlusion leads to atrophy of the ipsilateral lobe and to compensatory regeneration of the contralateral lobe. Adaptation of modern radiological imaging technologies to the small size of rodents made the visualization of rodent intrahepatic vascular anatomy possible. Advanced knowledge of the detailed intrahepatic 3D anatomy enabled the establishment of refined surgical techniques. The same technology allows the visualization of hepatic vascular regeneration. The development of modern histological image analysis tools improved the quantitative assessment of hepatic regeneration. Novel image analysis tools enable us to quantify reliably and reproducibly the proliferative rate of hepatocytes using whole-slide scans, thus reducing the sampling error. In this review, the refined rodent models and the newly developed imaging technology to study liver regeneration are summarized. This summary helps to integrate the current knowledge of liver regeneration and promises an enormous increase in hepatological knowledge in the near future. © 2014 S. Karger AG, Basel

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The compensatory hyperplasia (liver regeneration) following ligation of a portal branch is initiated before the atrophy of the deprived lobes

Cited by 32 publications

References 17 publications

Molecular mechanisms of apoptosis in the liver of rats after portal branch ligation with and without retrorsine

Molecular mechanisms of apoptosis in the liver of rats after portal branch ligation with and without retrorsine

Portal branch ligation induces a hepatic arterial buffer response, microvascular remodeling, normoxygenation, and cell proliferation in portal blood-deprived liver tissue

Rodent Models and Imaging Techniques to Study Liver Regeneration

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