Modelisation of the interraction between liver hemodynamics and regeneration for the study of post hepatectomy liver failure

La régénération hépatique après résection hépatique majeure ne se fait pas toujours de la même façon et une partie importante des facteurs déterminants de la régénération pourrait être liée aux constantes hémodynamiques hépatiques.Le but de nos travaux a été d'étudier cette relation en se basant notamment sur les modèles expérimentaux d'hépatectomie chez le gros animal. Nous avons étudié la régénération sur forme de volume mesuré en imagerie, examen anatomopathologique, prolifération des hépatocytes et des vaisseaux dans le parenchyme hépatique jusqu'à une reconstruction 3D du lobule hépatique.Nos résultats indiquent des liens forts entre l'hémodynamique et la qualité de la régénération et laissent entrevoir la possibilité d'agir sur les composantes hémodynamique.Liver regeneration after liver resection does not occur in the same way in different conditions. A major determining factor of the regeneration could be the hemodynamic environment of the regenerating liver.The aim of our work was to study the relationship between liver regeneration and hemodynamic parameters, based mainly on experimental models of liver resection in large animals. We studied regeneration as CT scan volume, histopathology, hepatocyte proliferation and vessel neoformation inside the liver parenchyma, up to 3D reconstruction of the liver lobule.Our results show important relationships between liver hemodynamics and liver regeneration and let imagine the possibility to modulate hemodynamic parameters in order to modify liver regeneration

Modélisation de l'interaction entre l'hémodynamique hépatique et la régénération hépatique dans l'étude de l'insuffisance hépatique post hépatectomie

Liver regeneration after liver resection does not occur in the same way in different conditions. A major determining factor of the regeneration could be the hemodynamic environment of the regenerating liver.The aim of our work was to study the relationship between liver regeneration and hemodynamic parameters, based mainly on experimental models of liver resection in large animals. We studied regeneration as CT scan volume, histopathology, hepatocyte proliferation and vessel neoformation inside the liver parenchyma, up to 3D reconstruction of the liver lobule.Our results show important relationships between liver hemodynamics and liver regeneration and let imagine the possibility to modulate hemodynamic parameters in order to modify liver regeneration.La régénération hépatique après résection hépatique majeure ne se fait pas toujours de la même façon et une partie importante des facteurs déterminants de la régénération pourrait être liée aux constantes hémodynamiques hépatiques.Le but de nos travaux a été d'étudier cette relation en se basant notamment sur les modèles expérimentaux d'hépatectomie chez le gros animal. Nous avons étudié la régénération sur forme de volume mesuré en imagerie, examen anatomopathologique, prolifération des hépatocytes et des vaisseaux dans le parenchyme hépatique jusqu'à une reconstruction 3D du lobule hépatique.Nos résultats indiquent des liens forts entre l'hémodynamique et la qualité de la régénération et laissent entrevoir la possibilité d'agir sur les composantes hémodynamique

Partial hepatectomy hemodynamics changes: Experimental data explained by closed-loop lumped modeling

International audienceThe liver function may be degraded after partial liver ablation surgery. Adverse liver hemody-namics have been shown to be associated to liver failure. The link between these hemodynamics changes and ablation size is however poorly understood. This article proposes to explain with a closed-loop lumped model the hemodynamics changes observed during twelve surgeries in pigs. The portal venous tree is modeled with a pressure-dependent variable resistor. The variables measured, before liver ablation, are used to tune the model parameters. Then, the liver partial ablation is simulated with the model and the simulated pressures and flows are compared with post-operative measurements. Fluid infusion and blood losses occur during the surgery. The closed-loop model presented accounts for these blood volume changes. Moreover, the impact of blood volume changes and the liver lobe mass estimations on the simulated variables is studied. The typical increase of portal pressure, increase of liver pressure loss, slight decrease of portal flow and major decrease in arterial flow are quantitatively captured by the model for a 75% hepatectomy. It appears that the 75% decrease in hepatic arterial flow can be explained by the resistance increase induced by the surgery, and that no hepatic arterial buffer response (HABR) mechanism is needed to account for this change. The different post-operative states, observed in experiments, are reproduced with the proposed model. Thus, an explanation for inter-subjects post-operative variability is proposed. The presented framework can easily be adapted to other species circulations and to different pathologies for clinical hepatic applications

Simplified technique for 75% and 90% hepatic resection with hemodynamic monitoring in large white swine model

International audienceBackground:Accurate measuring of the hepatic hemodynamic parameters in humans is inconvenient. Swine has been a favourite surgical model for the study of liver conditions due to many similarities with human livers. However, pigs cannot tolerate pedicle clamping and to reduce bleeding during resection a simplified technique is required.Aim:The aim of this study is to present a simplified technique for different percentages of hepatic resection in a porcine model.Methods:Twenty two consecutive large white pigs were operated with 75% and 90% liver resection. CT liver volumetry is performed before and after surgery. In both types of surgery, hemodynamic monitoring was performed using a specialised apparatus.Results:Resections were performed in both groups successfully. The residual volume in the planned 75% was 235 ±77 ml and 118 ±119 ml in the planned 90% resection.For 75% resection, the portal flow was reduced after resection by 8.13 ± 28%, which might be part of systemic circulatory depression. However, the portal pressure increased by 20.1 ± 51 %. The hepatic artery flow decreased by 63.86 ± 26.3 % as well as the pressure by 5 ±28 %. The central venous pressure at the start of surgery was 3.34 ± 1.9 mmHg and 2.8 ± 2.2 mmHg at the end of surgery. The portocaval pressure gradient was 4.4 ± 2.9 mmHg at the beginning of surgery and was 5.9 ± 2.8 mmHg at the end of surgery.For 90% resection, the portal flow decreased by 33.6±12.6% and the pressure increased by 104±58%. The hepatic artery flow decreased by 88±7% and the pressure decreased by 5±14.8%. The central venous pressure was 3.5±1.7 mmHg before resection and 3±2.5 mmHg after resection. The portocaval pressure gradient was 3.8±1.1 mmHg before resection and 8±3.7 mmHg after resection.The mean anaesthesia time was 6.6 ±1.05 hours and 6.9 ± 0.5 hours for 75% and 90% resection, respectively. The mean operative time was 4.6 ±0.9 hours and 5 ±0.7 hours for 75% and 90% resections, respectively. The mean time for hepatectomy was 1.23±0.76 hours and 2.4 ±0.1 hours for 75% and 90% resection, respectively. The mean time consumed in the measurements was 2.28±1.4 hours and 1.1 ±0.3 hours for 75% and 90% resections, respectively. The mean volume of aspirated fluid and blood in the 75% resection was 1062± 512 ml while it was 1050 ± 354 ml in 90% resections.Conclusions:The hereby described technique is simple and easily applicable for major liver resection in a porcine model. . Portal flow decreases after 90% resection more than in 75% due to the relative reduction of remnant hepatic mass. There was a larger increase in portal pressure following 90% compared to 75% resection. The hepatic artery flow decreases more in 90% than in 75% resections

Closed-loop cardiovascular system model and partial hepatectomy simulation

International audienceThe present work aims at developing a mathematical model in order to reproduce hemodynamics changes due to liver surgeries. First, a 0D closed-loop model is developed, to simulate hepatectomy and compute post-operative average values. Due to the closed loop, the surgery impact both on and from the whole circulation can be captured, including bleeding and infusion. Then, a one-dimensional artery model is implemented to improve the closed-loop model and simulate better the changes in arterial waveforms due to surgery

Kinetic scheme for arterial and venous blood flow, and application to partial hepatectomy modeling.

International audienceThe article introduces a kinetic scheme to solve the 1D Euler equations of hemo-dynamics, and presents comparisons of a closed-loop 1D-0D model with real measurements obtained after the hepatectomy of four pigs. Several benchmark tests show that the kinetic scheme compares well with more standard schemes used in the literature, for both arterial and venous wall laws. In particular, it is shown that it has a good behavior when the section area of a vessel is close to zero, which is an important property for collapsible or clamped vessels. The application to liver surgery shows that a model of the global circulation, including 0D and 1D equations, is able to reproduce the change of waveforms observed after different levels of hepatectomy. This may contribute to a better understanding of the change of liver architecture induced by hepatectomy

Kinetics of Hepatic Volume Evolution and Architectural Changes after Major Resection in a Porcine Model

International audienceBackground: The hepatic volume gain following resection is essential for clinical recovery. Previous studies have focused on cellular regeneration. This study aims to explore the rate of hepatic regeneration of the porcine liver following major resection, highlighting estimates of the early microarchitectural changes that occur during the cellular regeneration. Methods: Nineteen large white pigs had 75% resection with serial measurements of the hepatic volume, density, blood flow, and architectural changes.Results: The growth rate initially was 45% per day, then rapidly decreased and was accompanied by a similar pattern of hepatic fat deposition. The architectural changes showed a significant increase in the Ki67 expression (p < 0.0001) in the days following resection with a peak on the 2nd day and nearly normalized on day 7. The expression of CD31 increased significantly on the 2nd and 3rd days compared to the pre-resection samples (p = 0.03). Hepatic artery flow per liver volume remained at baseline ranges during regeneration. Portal flow per liver volume increased after liver resection (p < 0.001), was still elevated on the 1st postoperative day, then decreased. Correlations were significantly negative between the hepatic volume increase on day 3 and the hepatic oxygen consumption and the net lactate production at the end of the procedure (r = –0.82, p = 0.01, and r = –0.70, p = 0.03). Conclusion: The volume increase in the first days – a fast process – is not explained by cellular proliferation alone. The liver/body weight ratio is back to 50% of the preoperative value after 3 days to close to 100% volume regain on days 10–15

Transit time ultrasound perivascular flow probe technology is superior to MR imaging on hepatic blood flow measurement in a porcine model

International audienceBACKGROUND:The hepatic hemodynamics is an essential parameter in surgical planning as well as in various disease processes. The transit time ultrasound (TTUS) perivascular flow probe technology is widely used in clinical practice to evaluate the hepatic inflow, yet invasive. The phase-contrast-MRI (PC-MRI) is not invasive and potentially applicable in assessing the hepatic blood flow. In the present study, we compared the hepatic inflow rates using the PC-MRI and the TTUS probe, and evaluated their predictive value of post-hepatectomy adverse events.METHODS:Eighteen large white pigs were anaesthetized for PC-MRI and approximately 75% hepatic resection was performed under a unified protocol. The blood flow was measured in the hepatic artery (Qha), the portal vein (Qpv), and the aorta above the celiac trunk (Qca) using PC-MRI, and was compared to the TTUS probe. The Bland-Altman method was conducted and a partial least squares regression (PLS) model was implemented.RESULTS:The mean Qpv measured in PC-MRI was 0.55 ± 0.12 L/min, and in the TTUS probe was 0.74 ± 0.17 L/min. Qca was 1.40 ± 0.47 L/min in the PC-MRI and 2.00 ± 0.60 L/min in the TTUS probe. Qha was 0.17 ± 0.10 L/min in the PC-MRI, and 0.13 ± 0.06 L/min in the TTUS probe. The Bland-Altman method revealed that the estimated bias of Qca in the PC-MRI was 32% (95% CI: -49% to 15%); Qha 17% (95% CI: -15% to 51%); and Qpv 40% (95% CI: -62% to 18%). The TTUS probe had a higher weight in predicting adverse outcomes after 75% resection compared to the PC-MRI (β= 0.35 and 0.43 vs β = 0.22 and 0.07, for tissue changes and premature death, respectively).CONCLUSIONS:There is a tendency of the PC-MRI to underestimate the flow measured by the TTUS probes. The TTUS probe measures are more predictive of relevant post-hepatectomy outcomes