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World Journal of Gastroenterology 2017年第48期23卷 8443-8451页

作者： Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal The Liver Unit University Hospitals of BirminghamMindelsohn Way The Centre for Liver Research Institute for Biomedical ResearchUniversity of Birmingham

Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.

关键词： Autophagy Liver transplant Ischaemiareperfusion injury normothermic machine liver perfusion

Liver graft preservation methods during cold ischemia phase and normothermic machine perfusion

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World Journal of Gastrointestinal Surgery 2019年第3期11卷 126-142页

作者： Konstantin Y Tchilikidi Department of Surgery Altai State Medical University

The growing demand for donor organs requires measures to expand donor pool.Those include extended criteria donors, such as elderly people, steatotic livers,donation after cardiac death, etc. Static cold storage to reduce metabolic requirements developed by Collins in late 1960 s is the mainstay and the golden standard for donated organ protection. Hypothermic machine perfusion provides dynamic organ preservation at 4°C with protracted infusion of metabolic substrates to the graft during the ex vivo period. It has been used instead of static cold storage or after it as short perfusion in transplant center. normothermic machine perfusion(NMP) delivers oxygen, and nutrition at physiological temperature mimicking regular environment in order to support cellular function. This would minimize effects of ischemia/reperfusion injury.Potentially, NMP may help to estimate graft functionality before implantation into a recipient. Clinical studies demonstrated at least its non-inferiority or better outcomes vs static cold storage. Regular grafts donated after brain death could be safely preserved with convenient static cold storage. Except for prolonged ischemia time where hypothermic machine perfusion started in transplant center could be estimated to provide possible positive reconditioning effect. Use of hypothermic machine perfusion in regular donation instead of static cold storage or in extended criteria donors requires further investigation. Multicenter randomized clinical trial supposed to be completed in December 2021. Extended criteria donors need additional measures for graft storage and assessment until its implantation. NMP is actively evaluating promising method for this purpose.Future studies are necessary for precise estimation and confirmation to issue clinical practice recommendations.

关键词： Liver graft preservation Graft preservation solutions Static cold storage Hypothermic machine perfusion normothermic machine perfusion Ischemia-reperfusion injury Marginal grafts Donation after cardiac death Extended criteria donors Transpla complications

An Experience on normothermic Beating Heart Pulmonary Thromboendarterectomy

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World Journal of Cardiovascular Surgery 2019年第1期9卷 1-13页

作者： Akshay Kumar Bisoi Pradeep Ramakrishnan Sandeep Chauhan Manoj Kumar Sahu Naveen Chander Chandrasekharan Department of CTVS C N Centre All India Institute of Medical Sciences New Delhi India Department of Cardiac Anaesthesiology C N Centre All India Institute of Medical Sciences New Delhi India

Objective: To study the outcome of normothermic beating heart pulmonary thromboendarterectomy (PTE) performed in patients with chronic pulmonary thromboembolism. Methodology: A retrospective analysis of 15 patients who underwent PTE under normothermic beating heart cardio-pulmonary bypass from July 2009 to September 2018 was done. The patients were followed up with clinical assessment, transthoracic echocardiography and computerized tomographicangiography (CTA) for 1 month to 82 months. Results: Data were analysed for 15 consecutive patients. Mean age of the patients was 35.28 years and 10 patients were male. Pre-operatively 6 (40%) patients presented with New York Heart Association (NYHA) class II dyspnoea on exertion symptomatology, 7 (47%) were in NHYA class III, and 2 (13%) were in NYHA class IV. The preoperative and postoperative mean pulmonary artery pressures (mPAP) (mmHg) were 36.50 ± 11.3 and 20.21 ± 7.19, the systolic PAPs (mmHg) were 73.35 ± 14.12 and 35.21 ± 7.89 and the diastolic PAPs (mmHg) were 19.28 ± 8.60 and 12.85 ± 7.26 respectively. 2 (13%) patients had Jamieson’s type I and 12 (87%) had Jamieson type II disease. One patient (7%) expired on 9th postoperative day. All the patients had improved pulmonary gas exchange and did not require oxygen supplementation from 5th postoperative day;symptoms improved to NYHA class I & II in 12 (80%) & 3 (20%) of patients respectively. There was no reperfusion pulmonary edema or any neurologic complications. Postoperative echocardiogram showed improved right ventricular function and Computerised Tomographic Angiogram showed completeness of the procedure. Conclusion: Pulmonary thromboendarterectomy under normothermic beating heart cardiopulmonary bypass has good immediate postoperative results with significant progressive improvement in hemodynamics and quality of life during the course of follow-up. The results were not only comparable to those of the procedure done under deep hypothermic circulatory arrest by other centres but also without its associated adve

关键词： Pulmonary Thromboendarterectomy normothermic Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Beating Heart

EXPERIENCE OF normothermic COMPLETE HEPATIC VASCULAR EXCLUSION FOR EXTENSIVE HEPATECTOMY (REPORT OF 4 CASES)

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Journal of Pharmaceutical Analysis 1998年第1期12卷 67-73,94页

作者：张学渊石景森刘绍诰王作仁

This paper deals with an experience of normothermic complete hepatic vascular exclusionfor extensive hepatectomy. All the 4 cases suffered from primary'llver carcinoma. In one case, thelarge tumor was situated in the left lobe, and the other tumor was situated in the left lobe, and in therest of them, the tumor even occupied the greater Part or the right lobe with one or the patient's inferior vena cave being Invaded by tumor seriously. Clamps were applied to the abdominal aorta, on theportal triads and to the inferior vena cave below and above the liver. Blood Intake during operationwas from 1000 to 1200 millilitres Hemodynareic alterations during hepatic vascular isolation wereslight and temporary. Biochemical alterations during operation we.re mainly metabolic acidosis. Postoperatively, serum bilirubin and serum enzymes elevation, total protein and albumin decrease werethe principal biological changes. The hepatic specimens weighed from 1400 to 1850 grams. This technique greatly reduced intraoperative hemorrhage, increased operative safety and raised the resectional rate of liver.

关键词： hepatectomy normothermic hemodynamic biochemical alteration

Liver preservation prior to transplantation: Past, present, and future

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World Journal of Gastrointestinal Surgery 2019年第3期11卷 122-125页

作者： Marcio F Chedid Marcelo A Pinto Jose Felipe G Juchem Tomaz J M Grezzana-Filho Cleber R P Kruel Liver Transplant and Hepatobiliary Surgery Unit Hospital de Clinicas de Porto AlegreFederal University of Rio Grande do Sul (UFRGS)

Since Dr. Thomas Starzl performed the first series of successful liver transplants(LTs), important advances have been made in immunosuppression, operative techniques, and postoperative care. In 1988, Belzer's group reported the first successful LT using the University of Wisconsin preservation solution(UW).Since then, UW has replaced EuroCollins solution and allowed prolonged and safer preservation of liver, kidney, and pancreas allografts, thus contributing to the improvement of transplant outcomes. Although UW is still considered the standard of care in the United States and in several countries worldwide, a recent meta-analysis revealed similar LT outcomes among UW, Celsior solution, and the Institut Georges Lopez-1 preservation solution, which were slightly superior to those obtained with histidine-tryptophan-ketoglutarate preservation solution.Dynamic preservation has been recently developed, and liver allografts are preserved mainly through the following methods: hypothermic machine perfusion, normothermic machine perfusion, and subnormothermic machine perfusion. Their use has the potential advantage of improving clinical results in LT involving extended criteria donor allografts. Although associated with increased costs, techniques employing machine perfusion of liver allografts have been considered clinically feasible. This editorial focuses on recent advances and future perspectives in liver allograft preservation.

关键词： Liver transplantation University of Wisconsin preservation solution Institute Georges Lopez preservation solution Celsior preservation solution Histidine-tryptophanketoglutarate preservation solution Dymamic preservation normothermic ischemia normothermic preservation Hypotermic machine preservation Static cold prreservation

Liver transplantation with grafts obtained after cardiac death-current advances in mastering the challenge

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World Journal of Translational Medicine 2014年第2期3卷 58-68页

作者： Fateh Bazerbachi Nazia Selzner John B Seal Markus Selzner Department of Medicine University of Minnesota Department of Medicine University of TorontoMultiorgan Transplant Program Toronto General Hospital Department of Surgery University of Toronto Multiorgan Transplant Program Toronto General Hospital

The scarcity of donor livers has increased the interest in donation after cardiac death(DCD) as an additional pool to expand the availability of organs. However, the initial results of liver transplantation with DCD grafts have been suboptimal due to an increased rate of complications, as well as decreased graft survival. These challenges have led to many developments in DCD donation outcome, as well as basic and translational research. In this article we review the unique characteristics of DCD donors, nuances of DCD organ procurement, the effect of prolonged warm and cold ischemia times, and discuss major studies that compared DCD to donation after brain death liver transplantation, in terms of outcomes and complications. We also review the different methods of donor treatment that has been applied to ameliorate DCD organ outcome, and we discuss the role of machine perfusion techniques in organ reconditioning. We discuss the two major perfusionmodels, namely, hypothermic machine perfusion and normothermic machine perfusion; we compare both methods, and delineate their major differences.

关键词： Transplant hepatology Liver transplantation Organ donation Extended criteria donors Donation after cardiac death Ex-vivo liver perfusion normothermic machine perfusion Hypothermic machine perfusion