Reduced Hepatic Arterial Perfusion Impairs the Recovery From Focal Hepatic Venous Outflow Obstruction in Liver-Resected Rats

Huang, Hai; Deng, Meihong; Jin, Hao; Liu, Anding; Dahmen, Uta; Dirsch, Olaf

doi:10.1097/tp.0000000000000089

Cited by 5 publications

(16 citation statements)

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“…The pharmacological modulation of hepatic hemodynamics by vasoactive drugs might prevent the additional surgical risk caused by an additional surgical intervention such as splenectomy [6, 29]. By means of knowledge-based selection, we chose five substances out of more than 20 drug classes addressing different molecular pathways (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Partial hepatectomy was performed employing a modified resection technique described in detail previously [6]. In brief, the left lateral lobe, the left median lobe, the superior plus inferior caudate lobes, and the right superior plus inferior lobes were resected, leading to an estimated 70% reduction of liver mass.…”

Section: Methodsmentioning

confidence: 99%

“…Inhibition of NO-release by administrating L-N G -Nitroarginine methyl ester (L-NAME), an analog of arginine, aggravated liver damage. In contrast, the NO-release induced by the application of molsidomine, a NO donor, did not have a beneficial effect in terms of liver damage and hepatic regeneration despite a measurable effect on hepatic hemodynamics [6]. …”

Section: Introductionmentioning

confidence: 99%

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Modulation of hepatic perfusion did not improve recovery from hepatic outflow obstruction

Arlt

Wei

Xie

et al. 2017

BMC Pharmacol Toxicol

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BackgroundFocal hepatic venous outflow obstruction frequently occurs after extended liver resection and leads to a portal hypertension, arterial hypoperfusion and parenchymal necrosis.In this study, we investigated the pharmacological modulation of liver perfusion and hepatic damage in a surgical model of hepatic outflow obstruction after extended liver resection by administration of 5 different drugs in comparison to an operative intervention, splenectomy.MethodsMale inbred Lewis rats (Lew/Crl) were subjected to right median hepatic vein ligation + 70% partial hepatectomy. Treatment consisted of a splenectomy or the application of saline, carvedilol or isosorbide-5-mononitrate (ISMN) (5 mg · kg−1 respectively 7,2 mg · kg−1 per gavage 12 h−1). The splenectomy was performed during operation. The effect of the treatments on hepatic hemodynamics were measured in non-operated animals, immediately after operation (n = 4/group) and 24 h after operation (n = 5/group). Assessment of hepatic damage (liver enzymes, histology) and liver cell proliferation (BrdU-immunohistochemistry) was performed 24 h after operation. Furthermore sildenafil (10 μg · kg−1 i.p. 12h−1), terlipressin (0.05 mg · kg−1 i.v. 12 h−1) and octreotide (10 μg · kg−1 s.c. 12 h−1) were investigated regarding their effect on hepatic hemodynamics and hepatic damage 24 h after operation (n = 4/group).ResultsCarvedilol and ISMN significantly decreased the portal pressure in normal non-operated rats from 11,1 ± 1,1 mmHg (normal rats) to 8,4 ± 0,3 mmHg (carvedilol) respectively 7,4 ± 1,8 mmHg (ISMN). ISMN substantially reduced surgery-induced portal hypertension from 15,4 ± 4,4 mmHg to 9,6 ± 2,3 mmHg. Only splenectomy reduced the portal flow immediately after operation by approximately 25%. No treatment had an immediate effect on the hepatic arterial perfusion. In all treatment groups, portal flow increased by approximately 3-fold within 24 h after operation, whereas hepatic arterial flow decreased substantially. Neither treatment reduced hepatic damage as assessed 24 h after operation. The distribution of proliferating cells appeared very similar in all drug treated groups and the splenectomy group.ConclusionTransient relative reduction of portal pressure did not result in a reduction of hepatic damage. This might be explained by the development of portal hyperperfusion which was accompanied by arterial hypoperfusion.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-017-0155-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modulation of hepatic perfusion did not improve recovery from hepatic outflow obstruction

Arlt

Wei

Xie

et al. 2017

BMC Pharmacol Toxicol

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“…Liver resections and portal occlusions have also been combined with other interventions to better understand factors affecting hepatocyte proliferation and liver regeneration. These include interventions affecting hepatic perfusion such as right median hepatic vein ligation (Dirsch et al, 2008a ; Huang et al, 2014 ). To better understand the impact of additional damage to the portally ligated lobe, bile duct ligation was performed resulting in increased regeneration of the FLR.…”

Section: Clinical and Experimental Partmentioning

confidence: 99%

“…Fewer studies aimed for interfering by surgical or pharmacological interventions (e.g., splenectomy, drug treatment). Good examples are the reports by Huang et al ( 2014 ) and Arlt et al ( 2017 ), both of whom used a rat model of 70% PHx combined with right median hepatic vein ligation. This combined procedure mimics resection-associated FOO due to hepatic vein transection.…”

Section: Clinical and Experimental Partmentioning

confidence: 99%

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function

et al. 2021

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Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue. These forces are perceived by mechanosensors on parenchymal and non-parenchymal cells of the liver and regulate cell-cell and cell-matrix interactions as well as cellular signaling and metabolism. These interactions are key players in tissue growth and remodeling, a prerequisite to restore tissue function after PHx. Their dysregulation is associated with metabolic impairment of the liver eventually leading to liver failure, a serious post-hepatectomy complication with high morbidity and mortality. Though certain links are known, the overall functional change after liver surgery is not understood due to complex feedback loops, non-linearities, spatial heterogeneities and different time-scales of events. Computational modeling is a unique approach to gain a better understanding of complex biomedical systems. This approach allows (i) integration of heterogeneous data and knowledge on multiple scales into a consistent view of how perfusion is related to hepatic function; (ii) testing and generating hypotheses based on predictive models, which must be validated experimentally and clinically. In the long term, computational modeling will (iii) support surgical planning by predicting surgery-induced perfusion perturbations and their functional (metabolic) consequences; and thereby (iv) allow minimizing surgical risks for the individual patient. Here, we review the alterations of hepatic perfusion, biomechanical properties and function associated with hepatectomy. Specifically, we provide an overview over the clinical problem, preoperative diagnostics, functional imaging approaches, experimental approaches in animal models, mechanoperception in the liver and impact on cellular metabolism, omics approaches with a focus on transcriptomics, data integration and uncertainty analysis, and computational modeling on multiple scales. Finally, we provide a perspective on how multi-scale computational models, which couple perfusion changes to hepatic function, could become part of clinical workflows to predict and optimize patient outcome after complex liver surgery.

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Risk factors of delayed recovery from general anesthesia in patients undergoing radical biliary surgery

Zhang¹,

Pan²,

Tan³

et al. 2021

Medicine

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Delayed recovery (DR) is very commonly seen in the patients undergoing laparoscopic radical biliary surgery, we aimed to investigate the potential risk factors of DR in the patients undergoing radical biliary surgery, to provide evidences into the management of DR. Patients who underwent radical biliary surgery from January 1, 2018 to August 31, 2020 were identified. The clinical characteristics and treatment details of DR and no-DR patients were compared and analyzed. Multivariable logistic regression analyses were conducted to identify the potential influencing factors for DR in patients with laparoscopic radical biliary surgery. We included a total of 168 patients with laparoscopic radical biliary surgery, the incidence of postoperative DR was 25%. There were significant differences on the duration of surgery, duration of anesthesia, and use of intraoperative combined sevoflurane inhalation (all P < .05), and there were not significant differences on American Society of Anesthesiologists, New York Heart Association, tumor-lymph node- metastasis, and estimated blood loss between DR group and control group (all P > .05). Multivariable logistic regression analyses indicated that age ≥70 years (odd ratio [OR] 1.454, 95% confidence interval [CI] 1.146–1.904), body mass index ≥25 kg/m 2 (OR 1.303, 95% CI 1.102–1.912), alcohol drinking (OR 2.041, 95% CI 1.336–3.085), smoking (OR 1.128, 95% CI 1.007–2.261), duration of surgery ≥220 minutes (OR 1.239, 95% CI 1.039–1.735), duration of anesthesia ≥230 minutes (OR 1.223, 95% CI 1.013–1.926), intraoperative combined sevoflurane inhalation (OR 1.207, 95% CI 1.008–1.764) were the independent risk factors for DR in patients with radical biliary surgery (all P < .05). It is clinically necessary to take early countermeasures against various risk factors to reduce the occurrence of DR, and to improve the prognosis of patients.

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Reduced Hepatic Arterial Perfusion Impairs the Recovery From Focal Hepatic Venous Outflow Obstruction in Liver-Resected Rats

Abstract: Reduction of HAP through inhibition of nitric oxide production worsened the recovery from FHVOO. Drugs increasing HAP need to be evaluated to reverse the hyperperfusion-induced impairment of the spontaneous course after FHVOO.

Cited by 5 publications

References 30 publications

Modulation of hepatic perfusion did not improve recovery from hepatic outflow obstruction

Modulation of hepatic perfusion did not improve recovery from hepatic outflow obstruction

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function

Risk factors of delayed recovery from general anesthesia in patients undergoing radical biliary surgery

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