Automated Insulin Delivery - Continuous Blood Glucose Control During<i>Ex Situ</i>Liver Perfusion

Becker, Dustin; Eshmuminov, Dilmurodjon; Keller, R.; Mueller, Matteo; Borrego, Lucía Bautista; Hagedorn, Catherine; Duskabilova, Muhayyo; Tibbitt, Mark W.; Onder, Christopher H.; Clavien, Pierre‐Alain; Rohr, Philipp Rudolf von; Schüler, Martin; Hefti, Max

doi:10.1109/tbme.2020.3033663

Cited by 10 publications

(19 citation statements)

References 44 publications

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“…In addition, glucose metabolism in our group of untreated livers stabilized to blood glucose levels within the desired range (3.5–6.5 mmol/L), indicating liver functionality [ 20 , 52 ] without any addition of glucose or insulin within the 5 h of perfusion. However, a significant blood glucose increase was visible after 60 min of perfusion, which has been previously reported in the literature [ 37 , 52 , 53 , 54 , 55 ]. Becker et al [ 55 ] described the release of glucose resulting in high blood glucose within the first phase after reperfusion as a consequence of ischemia-reperfusion injury and subsequent decrease of glucose levels, indicating the recovery of the liver.…”

Section: Discussionsupporting

confidence: 71%

“…However, a significant blood glucose increase was visible after 60 min of perfusion, which has been previously reported in the literature [ 37 , 52 , 53 , 54 , 55 ]. Becker et al [ 55 ] described the release of glucose resulting in high blood glucose within the first phase after reperfusion as a consequence of ischemia-reperfusion injury and subsequent decrease of glucose levels, indicating the recovery of the liver. This was also shown by Izamis et al [ 56 ], who described glucose release due to glycogenolysis within the first 2 h of perfusion after ischemic times.…”

Section: Discussionsupporting

confidence: 71%

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Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling

et al. 2022

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Metabolic and toxic liver disorders, such as fatty liver disease (steatosis) and drug-induced liver injury, are highly prevalent and potentially life-threatening. To allow for the study of these disorders from the early stages onward, without using experimental animals, we collected porcine livers in a slaughterhouse and perfused these livers normothermically. With our simplified protocol, the perfused slaughterhouse livers remained viable and functional over five hours of perfusion, as shown by hemodynamics, bile production, indocyanine green clearance, ammonia metabolism, gene expression and histology. As a proof-of-concept to study liver disorders, we show that an infusion of free fatty acids and acetaminophen results in early biochemical signs of liver damage, including reduced functionality. In conclusion, the present platform offers an accessible system to perform research in a functional, relevant large animal model while avoiding using experimental animals. With further improvements to the model, prolonged exposure could make this model a versatile tool for studying liver diseases and potential treatments.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 71%

Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling

et al. 2022

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“…Such reconstruction is also proposed if the volume of the congestive area in liver remnant exceeds 20% [23]. Recent advances in liver machine perfusions may enable even ex vivo liver resection and vein reconstruction [24][25][26][27]. However, ex vivo liver resection may have the disadvantages of additional warm ischemia during portal and arterial anastomoses and is costly.…”

Section: Discussionmentioning

confidence: 99%

Left renal vein graft and in situ hepatic perfusion in hepatectomy for complete tumor invasion of hepatic veins: hemodynamic optimization and surgical technique

López-López

Garcı́a-López

Eshmuminov³

et al. 2022

Langenbecks Arch Surg

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Purpose Assessing hepatic vein reconstruction using a left renal vein graft and in situ hypothermic liver perfusion in an extended liver resection. Methods Patients included in this study were those with liver tumors undergoing curative surgery with resection and reconstruction of hepatic veins. Hepatic vein was reconstructed using a left renal vein graft. We describe the technical aspects of liver resection and vascular reconstruction, the key aspects of hemodynamic management, and the use of in situ hypothermic liver preservations during liver transection (prior to and during vascular clamping). Results The right hepatic vein was reconstructed with a median left renal venal graft length of 4.5 cm (IQR, 3.1–5.2). Creatinine levels remained within normal limits in the immediate postoperative phase and during follow-up. Median blood loss was 500 ml (IQR, 300–1500) and in situ perfusion with cold ischemia was 67 min (IQR, 60.5–77.5). The grafts remained patent during the follow-up with no signs of thrombosis. No major postoperative complications were observed. Conclusion Left renal vein graft for the reconstruction of a hepatic vein and in situ hypothermic liver perfusion are feasible during extended liver resection.

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“…The base perfusion protocol and machine have been previously reported. 7,10,11 In this study, the perfusion technology was further developed to minimize bacterial and fungal contamination.…”

Section: Liver Perfusion Machine and Protocolmentioning

confidence: 99%

Sources and prevention of graft infection during long‐term ex situ liver perfusion

Eshmuminov¹,

Mueller²,

Brugger

et al. 2021

Transplant Infectious Dis

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Introduction The use of normothermic liver machine perfusion to repair injured grafts ex situ is an emerging topic of clinical importance. However, a major concern is the possibility of microbial contamination in the absence of a fully functional immune system. Here, we report a standardized approach to maintain sterility during normothermic liver machine perfusion of porcine livers for one week. Methods Porcine livers (n = 42) were procured and perfused with blood at 34°C following aseptic technique and standard operating procedures. The antimicrobial prophylaxis was adapted and improved in a step‐wise manner taking into account the pathogens that were detected during the development phase. Piperacillin‐Tazobactam was applied as a single dose initially and modified to continuous application in the final protocol. In addition, the perfusion machine was improved to recapitulate partially the host's defense system. The final protocol was tested for infection prevention during one week of perfusion. Results During the development phase, microbial contamination occurred in 27 out of 39 (69%) livers with a mean occurrence of growth on 4 ± 1.6 perfusion days. The recovered microorganisms suggested an exogenous source of microbial contamination. The antimicrobial agents (piperacillin/tazobactam) could be maintained above the targeted minimal inhibitory concentration (8‐16 mg/L) only with continuous application. In addition to continuous application of piperacillin/tazobactam, partial recapitulation of the host immune system ex situ accompanied by strict preventive measures for contact and air contamination maintained sterility during one week of perfusion. Conclusion The work demonstrates feasibility of sterility maintenance for one week during ex situ normothermic liver perfusion.

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Automated Insulin Delivery - Continuous Blood Glucose Control DuringEx SituLiver Perfusion

Cited by 10 publications

References 44 publications

Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling

Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling

Left renal vein graft and in situ hepatic perfusion in hepatectomy for complete tumor invasion of hepatic veins: hemodynamic optimization and surgical technique

Sources and prevention of graft infection during long‐term ex situ liver perfusion

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