Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

Czigány, Zoltán; Iwasaki, Junji; Yagi, Shintaro; Nagai, Kazuyuki; Szíjártó, Attila; Üemoto, Shinji; Tolba, René

doi:10.1159/000437095

Cited by 23 publications

(18 citation statements)

References 111 publications

(178 reference statements)

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“…The present study was designed according to the principles of the ARRIVE (Animal Research: Reporting of In Viv o Experiments) guidelines and based on our review article on performing and reporting experimental studies in rat liver transplantation [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

et al. 2018

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BackgroundIschemic-reperfusion (IR) injury still represents a major concern in clinical transplantation, especially in the era of extreme organ shortage and extended criteria donor organs. In the present study we aimed to investigate the hepatoprotective effects of remote ischemic conditioning (RIC) in a rat model of arterialized orthotopic liver transplantation (OLT).MethodsMale Lewis rats were used (n = 144 / 72 OLT cases; 240–340g) as donors and recipients. Livers were flushed and stored in 4°C HTK-solution for 8h before implantation. Recipients were randomly allocated into three experimental groups: RIC 1, RIC 2, Control. In RIC 1, RIC 2 groups, RIC was applied in the recipient before hepatectomy or after reperfusion (4x5-5min IR via clamping the infrarenal aorta), respectively. Animals were sacrificed at 1, 3, 24, 168h post-reperfusion (n = 6 recipient/group/time point). Hepatocellular injury, graft circulation, serum cytokines, tissue redox-stress and adenosine-triphosphate (ATP) levels have been assessed. Additional markers were analyzed, using Western blotting and reverse-transcription polymerase chain reaction.ResultsRIC 1 group showed significantly (p<0.05) improved portal venous and microcirculation flow as well as velocity. RIC has significantly reduced tissue injury according to the serum levels of transaminases and results of histopathological evaluation. Reduced TUNEL-staining (p<0.01 RIC 1–2 vs. Control) and elevated pBAD/BAD ratio was detected in the RIC groups (p<0.01 RIC 1 vs. Control). Supporting findings were obtained from measurements of serum IL-10 as well as tissue malondialdehyde and ATP levels. Hemoxygenase-1 (HO-1) mRNA-expression was significantly higher in RIC 1 compared to Control (p<0.05 RIC 1 vs. Control).ConclusionThese results suggest that RIC might confer potent protection against the detrimental effects of IR injury including tissue damage, apoptosis, graft circulation, inflammation, tissue energetic status in OLT. HO-1 overexpression might play an orchestrating role in RIC mediated organ protection. An earlier intervention (RIC 1 protocol) was more effective than remote conditioning after graft reperfusion.

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Section: Methodsmentioning

confidence: 99%

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

et al. 2018

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“…The mouse is the most commonly used animal, and several mouse models have been developed 20. In 1973, Lee et al reported the first orthotopic liver transplantation in the rat, which consisted of performing an extracorporeal shunt between the portal and jugular vein at the recipient and posterior anastomosis of the implant to the hepatic vein, the portal vein and the recipient's aorta 21.…”

Section: Discussionmentioning

confidence: 99%

Mild hypothermia during the reperfusion phase protects mitochondrial bioenergetics against ischemia-reperfusion injury in an animal model of ex-vivo liver transplantation—an experimental study

et al. 2019

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The organ preservation paradigm has changed following the development of new ways to preserve organs. The use of machine perfusion to preserve organs appears to have several advantages compared with conventional static cold storage. For liver transplants, the temperature control provided by machine perfusion improves organ preservation. In this experimental study, we measured the effects of different temperatures on mitochondrial bioenergetics during the reperfusion phase. An experimental model of ex-vivo liver transplantation was developed in Wistar rats (Rattus norvegicus). After total hepatectomy, cold static preservation occurred at 4ºC and reperfusion was performed at 37ºC and 32ºC using a Langendorff system. We measured parameters associated with mitochondrial bioenergetics in the livers. Compared with the livers that underwent normothermic reperfusion, mild hypothermia during reperfusion caused significant increases in the mitochondrial membrane potential, the adenosine triphosphate content, and mitochondrial respiration, and a significant reduction in the lag phase (all P < 0.001). Mild hypothermia during reperfusion reduced the effect of ischemia-reperfusion injury on mitochondrial activity in liver tissue and promoted an increase in bioenergetic availability compared with normothermic reperfusion.

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“…Over the past years, several comprehensive studies have been published on novel strategies for reducing the use of animals and training candidates on theoretical and practical levels without living subjects [21-23]. …”

Section: Considerations On Microsurgical Training Conceptsmentioning

confidence: 99%

“…They showed a high satisfaction, especially among students residing far from their training centers. Today, free-of-charge video platforms are widely available and even scientific video journals are gaining ground; therefore, the role of quality and didactic training videos in surgical training and in its international standardization is highly emphasized [23, 26, 27]. …”

Section: Considerations On Microsurgical Training Conceptsmentioning

confidence: 99%

“…These records can be analyzed to visualize learning curves, e.g., time, suture placement, handling, survival, and complication rates in more complex surgical models such as transplantation [23, 24, 63-65]. Within our group we used microscopic video recordings to evaluate the process of skill acquisition during the training of rat orthotopic liver transplantation [23]. Recordings were assessed by trainees to identify unnecessary movements or false techniques with the help of the supervisors.…”

Section: Assessment Tools and Clinical Translation Of Microsurgical Smentioning

confidence: 99%

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Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM)

et al. 2017

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Background: Expectations towards surgeons in modern surgical practice are extremely high with minimal complication rates and maximal patient safety as paramount objectives. Both of these aims are highly dependent on individual technical skills that require sustained, focused, and efficient training outside the clinical environment. At the same time, there is an increasing moral and ethical pressure to reduce the use of animals in research and training, which has fundamentally changed the practice of microsurgical training and research. Various animal models were introduced and widely used during the mid-20th century, the pioneering era of experimental microsurgery. Since then, high numbers of ex vivo training concepts and quality control measures have been proposed, all aiming to reduce the number of animals without compromising quality and outcome of training. Summary: Numerous microsurgical training courses are available worldwide, but there is no general agreement concerning the standardization of microsurgical training. The major aim of this literature review and recommendation is to give an overview of various aspects of microsurgical training. We introduce here the findings of a previous survey-based analysis of microsurgical courses within our network. Basic principles behind microsurgical training (3Rs, good laboratory practice, 3Cs), considerations around various microsurgical training models, as well as several skill assessment tools are discussed. Recommendations are formulated following intense discussions within the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM), based on scientific literature as well as on several decades of experience in the field of experimental (micro)surgery and preclinical research, represented by the contributing authors. Key Messages: Although ex vivo models are crucial for the replacement and reduction of live animal use, living animals are still indispensable at every level of training which aims at more than just a basic introduction to microsurgical techniques. Modern, competency-based microsurgical training is multi-level, implementing different objective assessment tools as outcome measures. A clear consensus on fundamental principles of microsurgical training and more active international collaboration for the sake of standardization are urgently needed.

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Improving Research Practice in Rat Orthotopic and Partial Orthotopic Liver Transplantation: A Review, Recommendation, and Publication Guide

Cited by 23 publications

References 111 publications

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

Mild hypothermia during the reperfusion phase protects mitochondrial bioenergetics against ischemia-reperfusion injury in an animal model of ex-vivo liver transplantation—an experimental study

Defining Standards in Experimental Microsurgical Training: Recommendations of the European Society for Surgical Research (ESSR) and the International Society for Experimental Microsurgery (ISEM)

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