Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Bonsignore, Pasquale (2014) Sviluppo di biomarkers per la determinazione e la valutazione prognostica della ripresa funzionale epatica post trapianto, nel fegato marginale e nel non heart beating donor. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF - Versione accettata
1805Kb

Abstract (inglese)

ABSTRACT
Background
One of the most crucial issues in liver transplantation is the gap between the increasing number of patients waiting for a transplant and the shortage of available grafts. This limitation has led many liver transplant units to include for surgery organs defined as “marginal” or “sub-optimal” due to hepatic steatosis or sourcing from non-heart-beating donors (NHBD). In turn, the marginality of these organ donors is proportional to a high incidence of liver dysfunction after transplantation due mainly to more severe ischemia-reperfusion injury events. The use of new methods of preservation of hepatic grafts like Machine Perfusion becomes necessary, especially for its ability to reduce the damage of ischaemia-reperfusion in hypothermia.
This opens an interest towards the use of alternative methods in preserving hepatic graft as Machine Perfusion, able to reduce this type of insults and allow the dosage of biomarkers that can predict the extent of damage ischemia-reperfusion injury and the quality of functional recovery of the graft after transplantation.
The great potential of this system in the context of organ preservation and the numerous studies in the literature led us to investigate this issue.

Purpose
The aim of our work was to carry out an experimental model of Machine Perfusion (MP) for the preservation of livers procured from non heart-beating donor, as a viable alternative to the traditional Cold storage (CS) at 4°C.
A further aim of our project was to identify biomarkers that can be used as predictors of postoperative graft damage.

Material and methods
We used 10 Landrace pigs of about 20 kg to which we performed, 60 minutes after cardiac arrest, total hepatectomy, thus harvesting the liver. The animals were divided into two groups: in the first group (Group A) 5 livers was preserved for 6 hours in MP at 20° C. In the second group (Group B) 5 livers was stored for 6 hours in CS. In all study groups the period of preservation was followed by reperfusion in normothermic MP (37 °) with whole oxygenated blood previously collected from the donor animal for 2 hours to assess the response to reperfusion. During the experiment blood samples and histological specimens were collected.

Results
Graft preservation by Machin perfusion at 20°C is superior compared to the Cold Storage, both from biochemical (AST, ALT, LDH, lactate) and histological standpoint (necrosis and congestion).
The dose of AST, ALT, LDH and lactate has proven be a reliable parameter for the assessment of organ damage and functional recovery of the graft liver. The dosage of cytokines such as IL1, IL6, TNF alpha showed no significance.

Conclusion
These experimental evidences highlight the effectiveness of a preservation with continuous perfusion at 20° C on a large animal model. Both from biochemical that histological standpoint, we have observed that Machine Perfusion in moderate hypothermia is beneficial in the preservation of the graft and offers the considerable advantage of being able to test, during perfusion, biomarkers that can predict hepatic graft recovery, before transplant, in order to reduce the incidence of post-transplant graft disfunction.

Abstract (italiano)

Riassunto
Premesse generali
Nell’ambito del trapianto di fegato, uno dei problemi più importanti non ancora risolti è la grande discrepanza tra la richiesta di organi e la risorsa di donazioni. Il ricorso ai così detti organi “marginali”, come quelli dei donatori a cuore non battente e con steatosi maggiore del 60%, potrebbe consentire di ampliare in maniera sensibile il pool degli organi disponibili per trapianto. L’impiego di questi fegati però è associato ad un’alta frequenza di Primary Disfunction postoperatoria a causa del danno che si sviluppa nel corso della preservazione in Cold Storage, nel contesto del processo di ischemia-riperfusione in ipotermia estrema (4°C). Si apre un’area di interesse di ricerca verso l’utilizzo di metodiche alternative nella conservazione del graft epatico come la Machine Perfusion, in grado di ridurre questo tipo di insulti e di consentire il dosaggio di biomarkers in grado di predire l’entità del danno da ischemia-riperfusione e la qualità della ripresa funzionale del graft dopo trapianto.
Le grandi potenzialità di questo sistema nell’ambito della preservazione d’organo e i numerosi lavori in letteratura ci hanno spinto ad approfondire questa tematica.

Scopo dello studio
L’obiettivo del nostro lavoro è stato quello di realizzare un modello sperimentale di Machine Perfusion per la preservazione di fegati prelevati da donatore a cuore non battente, come valida alternativa alla preservazione tradizionale in Cold storage a 4°C.
Ulteriore scopo del nostro progetto è stato quello di identificare eventuali biomarcatori in grado di predire l’entità del danno da ischemia-riperfusione e la qualità della ripresa funzionale del graft dopo trapianto di fegato da donatore a cuore non battente.

Materiali e metodi
Per questi esperimenti abbiamo utilizzato 10 maiali Landrace di circa 20 Kg ai quali abbiamo praticato, 60 minuti dopo l’arresto cardiaco, un’epatectomia totale, prelevando così il fegato. Gli animali sono stati suddivisi in due gruppi di 5 ciascuno: nel primo gruppo (Gruppo A) il fegato prelevato è stato perfuso in MP (Machine perfusion) per sei ore con soluzione di Celsior a 20°C. Nel secondo gruppo (Gruppo B) il fegato prelevato nei 5 animali è stato conservato per 6 ore in CS (Cold storage). In tutti i gruppi di studio il periodo di preservazione è stato seguito da un periodo di rewarming inteso come riperfusione dell’organo con sangue autologo in normotermia (37°) per due ore per valutare la risposta alla riperfusione. Durante tutte le otto ore dell’esperimento sono stati raccolti campioni ematici e istologici.

Risultati
Dal punto di vista biochimico (AST, ALT, LDH) e istologico (necrosi e congestione) la preservazione mediante perfusione a 20°C si è dimostrata superiore rispetto al Cold Storage.
Il dosaggio di AST, ALT, Acido lattico ed LDH si è dimostrato essere un parametro attendibile per la valutazione del danno d’organo e della ripresa funzionale del graft epatico. Il dosaggio di citochine quali IL1, IL6, TNf alfa non ha mostrato alcuna significatività.

Conclusioni
Queste evidenze sperimentali mettono in rilievo l’efficacia di una preservazione con macchina a perfusione continua a 20°C sul grande animale. Sia dal punto di vista biochimico che istologico, infatti, abbiamo osservato che la Machine Perfusion in moderata ipotermia è di beneficio nella preservazione del graft ed offre il notevole vantaggio di poter testare, durante la perfusione, biomarcatori che possono predire l’eventuale ripresa funzione dell’organo, prima dell’esecuzione del trapianto, al fine di ridurre l’incidenza di disfunction del graft post trapianto.

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Cillo, Umberto
Dottorato (corsi e scuole):Ciclo 26 > Scuole 26 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > EPATOLOGIA E CHIRURGIA EPATOBILIARE E TRAPIANTOLOGICA
Data di deposito della tesi:22 Gennaio 2014
Anno di Pubblicazione:20 Gennaio 2014
Parole chiave (italiano / inglese):donatori a cuore non battente, non heart beating donor, danno da ischemia riperfusione, ischemia reperfusion injury, donatori marginali, marginal donor, trapianto di fegato, liver transplantation
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/18 Chirurgia generale
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina
Codice ID:6318
Depositato il:17 Nov 2014 09:28
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

-Cameron AM, Ghobrial RM, Yersiz H, Farmer DG, Lipshutz GS, Gordon SA, et al. Optimal utilization of donor grafts with extended criteria: a single-center experience in over 1000 liver transplants. Ann Surg 2006;243:748-753; discussion 753-745. Cerca con Google

-European Liver Transplant Registry. Available at: http://www.eltr.org. Accessed September 2013 Vai! Cerca con Google

-Kauffman HM, McBride MA, Cherikh WS, Spain PC, Delmonico FL. Transplant tumor registry: donors with central nervous system tumors. Transplantation 2002;73:579-582 Cerca con Google

. Cerca con Google

-Buell JF, Alloway RR, Steve Woodle E, Trofe J, Sethuraman G, Hanaway MJ, et al. How can donors with a previous malignancy be evaluated? Donors with central nervous system malignancies: are they truly safe? J Hepatol 2006;45:503-507. Cerca con Google

-Sampietro R, Goffette P, Danse E, De Reyck C, Roggen F, Ciccarelli O, et al. Extension of the adult hepatic allograft pool using split liver transplantation. Acta Gastroenterol Belg 2005;68:369-375. Cerca con Google

-Humar A, Ramcharan T, Sielaff TD, Kandaswamy R, Gruessner RW, Lake JR, et al. Split liver transplantation for two adult recipients: an initial experience. Am J Transplant 2001;1:366-372. Cerca con Google

-Merion RM, Rush SH, Dykstra DM, Goodrich N, Freeman RB Jr, Wolfe RA. Predicted lifetimes for adult and pediatric split liver versus adult whole liver transplant recipients. Am J Transplant 2004;4:1792-1797. Cerca con Google

-Noujaim HM, Gunson B, Mayer DA, Mirza DF, Buckels JA, Candinas D, et al. Worth continuing doing ex situ liver graft splitting? A single-center analysis. Am J Transplant 2003;3:318-323. Cerca con Google

-Shneider BL, Emre S. Pediatric liver transplantation: past, present, and future. Liver Transpl 2006; 12: 511-513 Cerca con Google

-Tanaka K. Progress and future in living donor liver transplantation. Keio J Med 2003; 52: 73-79 Cerca con Google

-Sugawara Y, Makuuchi M. Living donor liver transplantation:present status and recent advances. Br Med Bull 2005; 75:15-28 Cerca con Google

-Lo CM, Fan ST, Liu CL, Chan JK, Lam BK, Lau GK, Wei WI, Wong J. Minimum graft size for successful living donor liver transplantation. Transplantation 1999; 68: 1112-1116 Cerca con Google

-Ben-Haim M, Emre S, Fishbein TM, Sheiner PA, Bodian CA,Kim-Schluger L, Schwartz ME, Miller CM. Critical graft sizein adult-to-adult living donor liver transplantation: impact ofthe recipient's disease. Liver Transpl 2001; 7: 948-953 Cerca con Google

-Ghobrial RM, Busuttil RW. Future of adult living donor liver transplantation. Liver Transpl 2003; 9: S73-S79 Cerca con Google

- Serracino – Inglott FS, Habib NA, Mathie R. Hepatic ischemia – reperfusion injury Am J Surg; 2001 181: 160 – 166 Cerca con Google

-Selzner N, Rudiger H, graf O, Clavien PA Protective strategies against Ischemic Injury of the Liver. Gastroenterology 2003; 125:917-936 Cerca con Google

- Montalvo-Jave EE, Escalante-Tattersfield TE, Ortega-Salgado JA, Pina E, Geller DA Factors in the pathophysiology of the liver – ischemia reperfusion injury. J Surg Res 2008 June 1; 147 (1): 153-159 Cerca con Google

-Jaeschke H Molecular mechanisms of hepatic – ischemia reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003; 284: G15-26 Cerca con Google

-Mc Cuskey RS Morphological mechanism for regulating blood flow through hepatic sinusoids. Liver 2000; 20: 3-7 Cerca con Google

-Ramalo FS, Fernandez-Monteiro IF, Rosello-Catafau J, Peralta C Hepatic microcirculatory failure. Acta Cir Bras 2006; 21 Suppl. 1 Cerca con Google

-Clemens MG, Zhang JX, Regulation of sinusoidal perfusion: in vivo methodology and control by endothelins. Semin Liver Dis 1999; 19:383-96 Cerca con Google

-Vollmar B, Richter S, Menger Md Leukocyte stasis in hepatic sinuosoids. Am J Physiol 1996; 270:G798-803 Cerca con Google

-Zhang JX, Jones DV, Clemens MG Effect of activation on neutrophil-induced hepatic microvascular injury in isolated rat liver. Shock 1994; 1:273-8 Cerca con Google

-Nakamura S, Nishiyama R, Serizawa A, Yokoi Y, Suzuki S, Konno H, Baba S, Muro H Hepatic release of endoyhelin-1 after warm ischemia. Reperfusion injury and its hemodynamic effect. Transplantation 1995; 59: 679-84 Cerca con Google

-Pannen BH New insights into the regulation of hepatic blood flow after ischemia and reperfusion. Anesth Analg 2002; 94: 1448-57 Cerca con Google

-Urakami A, Todo S, Zhu Y, Zhang S, Jin MB, Ishikazi N, Shimamura T, Totsuka E, Subbotin v, Lee R, Starzl TE Attenuation of ischemic liver injury by monoclonal anti-endothelin antibody, AwETN40. J Am Coll Surg 1997; 185; 358-64 Cerca con Google

-Shah V, Kamath PS Nitric oxide in liver transplantation: pathobiology and clinical implications. Liver Transpl 2003; 9: 1-11 Cerca con Google

-Peralta C, Rull R, Rimola A, Deulofeu R, Rosello.Catafau J, Gelpi E, Rodes J Cerca con Google

Endogenous nitric oxide and exogenous nitric oxide supplementation in hepatic ischemia – reperfusion injury in the rat. Transplantation 2001; 71: 529-36 Cerca con Google

-Pannen Bh, Al-Adili F, Bauer M, Clemens MG, Geiger KK Role of endothelins and nitric oxide in hepatic reperfusion injury in the rat. Hepatology 1998; 27: 755-64 Cerca con Google

-Kawachi S, Hines IN, Laroux FS, Hoffman J, Bharwani S, Gray L, Leffer D, Grisham MB Nitric oxide synthase and postischemic liver injury. Biochem Biophys Res Commun 2000, 276: 851-4 Cerca con Google

-Hur GM, Ryu YS, Yun HY, Jeon BH, Kim YM, seok JH, Lee JH Hepatic ischemia/reperfusion in rats induces iNOS gene transcription by activation of NF-kappaB. Biochem Biophys Res Commun 1999; 261: 917-22 Cerca con Google

-Glantzounis GK, Salcinski HJ, Yang W, Davidson BR, Seifalian AM The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review. Liver Transpl 2005; 11: 1031-47 Cerca con Google

-Teoh NC, Farrell GC Hepatic ischemia reperfusion injury: Pathogenic mechanism and basis for hepatoprotection. J Gastr Hepat 2003; 18: 891-902 Cerca con Google

-St Peter SD, Imber CJ, Friend PJ. Liver and kidney preservation by perfusion. Lancet 2002;359:604–613. Cerca con Google

-Garcia-Valdecasas JC, Tabet J, Valero R, Deulofeu R, Taura P, Rull R, et al. Evaluation of ischemic injury during liver procurement from non-heart-beating donors. Eur Surg Res 1999;31:447–456. Cerca con Google

-Schon MR, Kollmar O, Wolf S, Schrem H, Matthes M, Akkoc N, et al. Liver transplantation after organ preservation with normothermic extracorporeal perfusion. Ann Surg 2001;233:114–123. Cerca con Google

-St Peter SD, Imber CJ, Lopez I, Hughes D, Friend PJ. Extended preservation of non-heart-beating donor livers with normothermic machine perfusion. Br J Surg 2002;89:609–616. Cerca con Google

-Schon MR, Hunt CJ, Pegg DE, Wight DG. The possibility of resuscitating livers after warm ischemic injury. Transplantation 1993;56:24–31. Cerca con Google

-Lee CY, Zhang JX, Jones JW Jr, Southard JH, Clemens MG. Functional recovery of preserved livers following warm ischemia: improvement by machine perfusion preservation. Transplantation 2002;74:944–951. Cerca con Google

-Lee CY, Jain S, Duncan HM, Zhang JX, Jones JW, Jr., Southard JH, Clemens MG. Survival transplantation of preserved nonheart- beating donor rat livers: preservation by hypothermic machine perfusion. Transplantation 2003;76:1432–1436. Cerca con Google

-Saad S, Minor T, Kotting M, Fu ZX, Hagn U, Paul A, Nagelschmidt M. Extension of ischemic tolerance of porcine livers by cold preservation including postconditioning with gaseous oxygen. Transplantation 2001;71:498–502. Cerca con Google

-Ohwada S, Sunose Y, Aiba M, Tsutsumi H, Iwazaki S, Totsuka O, et al. Advantages of Celsior solution in graft preservation from non-heart-beating donors in a canine liver transplantation model. J Surg Res 2002;102:71–76. Cerca con Google

-Abt P, Crawford M, Desai N, Markmann J, Olthoff K, Shaked A. Liver transplantation from controlled non-heart-beating donors: an increased incidence of biliary complications. Transplantation 2003; 75: 1659-1663 Cerca con Google

-Abt PL, Desai NM, Crawford MD, Forman LM, Markmann JW, Olthoff KM, Markmann JF. Survival following liver transplantation from non-heart-beating donors. Ann Surg 2004; 239: 87-92 Cerca con Google

-Reddy S, Zilvetti M, Brockmann J, McLaren A, Friend P. Liver transplantation from non-heart-beating donors: current status and future prospects. Liver Transpl 2004; 10: 1223-1232 Cerca con Google

-Balupuri S, Buckley P, Mohamad M, et al. Early results of a nonheartbeating donor (NHBD) program with machine perfusion. Transpl Int. 2000;13(suppl 1):255–258. Cerca con Google

-Muiesan P, Ghirlanda R, Jassem W, Melendez H, O’Grady J, Bowles M, Rela M, Heaton N. Single-center experience with liver transplantation from controlled Non-Heartbeating donors- A viable source of grafts. Ann Surg 2005; 242 (5): 732-738 Cerca con Google

-Nocito A, El-Badry AM, Clavien PA. When is steatosis too much for transplantation? J Hepatol 2006; 45: 494–499. Cerca con Google

-Merion RM, Goodrich NP, Feng S. How can we define expandedcriteria for liver donors? J Hepatol 2006; 45: 484–488. Cerca con Google

-Deshpande R, Heaton N. Can non-heart-beating donors replace cadaveric heart-beating liver donors? J Hepatol 2006; 45: 499–503. Cerca con Google

-Strasberg SM, Howard TK, Molmenti EP, Hertl M. Selecting donor livers: Risk factors for poor function after orthotopic liver transplantation. Hepatology 1994; 20: 829–838. Cerca con Google

-Fuller BJ, Lee CY. Hypothermic perfusion preservation: The future of organ preservation revisited? Cryobiology 2007; 54: 129–145. Cerca con Google

-van der Plaats A, ‘t Hart NA, Verkerke GJ, Leuvenink HGD, PlegRJ, Rakhorst G. Hypothermic machine perfusion in liver transplantation revisited: Concepts and criteria in the new millenium. Ann Biomed Eng 2004; 32: 623–631. Cerca con Google

-Schreinemachers M-CJM, Doorschodt BM, van Gulik TM. Machine perfusion preservation of the liver: A worthwile clinical activity? Curr Opin Organ Transplant 2007; 12: 224–230. Cerca con Google

-Maathuis MH, Leuvenink HGD, Ploeg RJ. Perspectives in organ preservation. Transplantation 2007; 83: 1289–1298. Cerca con Google

-Butler AJ, Rees MA, Wight DG et al. Successful extracorporeal porcine liver perfusion for 72 hr. Transplantation 2002; 77: 1212–1218. Cerca con Google

-Imber CJ, St Peter SD, de Cenarruzabeitia IL et al. Advantages of normothermic perfusion over cold storage in liver preservation. Transplantation 2002; 73: 701–709. Cerca con Google

-Vajdova K, Smrekowa R,Mislanova C, Kukan M, Lutterova M. Cold preservation induced sensitivity of rat hepatocyte function to rewarming injury and its prevention by short-term reperfusion. Hepatology 2000; 32: 289–296. Cerca con Google

-Iwane T, Akamatsu Y, Narita T, Nakamura A, Satomi S. The effect of perfusion prior to cold preservation and addition of biliverdin on the liver graft from non-heart-beating donors. Transplantation Proc 2006; 38: 3358–3361. Cerca con Google

-Tolboom H, Pouw R, Uygun K et al. A model for normothermic preservation of the rat liver. Tissue Eng 2007; 13: 2143–2151. Cerca con Google

-Fondevila C, Hessheimer AJ, Ruiz A et al. Liver transplant using donors after unexpected cardia death: Novel preservation protocol and acceptance criteria. Am J Transplant 2007; 7: 1849–1855. Cerca con Google

-Reddy SP, Bhattacharjya S, Maniakin N et al. Preservation of porcine non-heart beating donor livers by sequential cold storage and warm perfusion. Transplantation 2004; 77: 1328–1332. Cerca con Google

-Reddy S, Greenwood J, Maniakin N et al. Non-heart beating donor porcine livers: The adverse effect of cooling. Liver Transplant 2005; 11: 35–38. Cerca con Google

-Compagnon P, Clement B, Campion J, Boudjema K. Effects of hypothermic machine perfusion on rat liver function depending on the route of perfusion. Transplantation 2001; 72: 606–614. Cerca con Google

-van der Plaats A, Maathuis MH, ‘t Hart NA et al. The Groningen hypothermic liver perfusion pump: Functional evaluation of a new machine perfusion system. Ann Biomed Eng 2006; 34: 1924–1934. Cerca con Google

-‘t Hart NA, van der Plaats A, Moers C et al. Development of the isolated dual perfused rat liver model as an improved reperfusion model for transplantation research. Int J Artif Organs 2006; 29: 219–227. Cerca con Google

-Guarrera JV, Estevez J, Boykin J et al. Hypothermic machine perfusion of liver grafts for transplantation: Technical development in human discard and miniature swine models. Transplant Proc 2005; 37: 323–325. Cerca con Google

-Pienaar BH, Lindell SL, van Gulik T, Southard JH, Belzer FO. Seventy-two-hour preservation of the canine liver by machine perfusion. Transplantation 1990; 49: 258–260. Cerca con Google

-Lee CY, Jain S, Duncan HM et al. Survival transplantation of preserved non-heart-beating donor rat livers: Preservation by hypothermic machine perfusion. Transplantation 2003; 76: 1432–1436. Cerca con Google

-Dutkowski P, Furrer K, Tian Y, Graf R, Clavien PA. Novel short term hypothermic oxygenated perfusion (HOPE) system prevents injury in rat liver graft from non-heart beating donor. Ann Surg 2006; 244: 968–976. Cerca con Google

-de Rougemont O, Breitenstein S, Leskosek B, Weber A, Graf R, Clavien PA. One hour hypotermic oxygenated perfusion (HOPE) protects nonviable liver allograft donated after cardiac death. Ann Surg 2009; 250: 674-682 Cerca con Google

-Jain S, Xu H, Duncan H et al. Ex vivo study of flow dynamics and endothelial cell structure during extended hypothermic machine perfusion preservation of livers. Cryobiology 2004; 48: 322–332. Cerca con Google

-Xu H, Lee CY, Clemens MG, Zhang JX. Prolonged hypothermic machine perfusion preserves hepatocellular function but potentiates endothelial cell dysfunction in rat livers. Transplantation 2004; 77: 1676–1682. Cerca con Google

-’t Hart NA, van der Plaats A, Leuvenink HG et al. Determination of an adequate perfusion pressure for continuous dual vessel hypothermic machine perfusion of the rat liver. Transplant Int 2007;20: 343–352. Cerca con Google

-Vajdova K, Graf R, Clavien PA. ATP-supplies in the cold preserved liver: A long neglected factor of viability. Hepatology 2002; 36:1543–1552. Cerca con Google

-Dutkowski P, Graf R, Clavien PA. Rescue of the cold preserved rat liver by hypothermic oxygenated machine perfusion. Am J Transplant 2006; 6: 903–912. Cerca con Google

-Manekeller S, Minor T. Possibilty of conditioning predamaged grafts after cold storage: Influences of oxygen and nutritive stimulation. Transplant Int 2006; 19: 667–674. Cerca con Google

-Mitchell SJ, Churchill TA, Winslet MC, Fuller BJ. Energy metabolism following prolonged hepatic cold preservation: Benefits of interrupted hypoxia on the adenine nucleotide pool in rat liver. Cryobiology 1999; 39: 130–137. Cerca con Google

-Bessems M, Doorschodt BM, van Marie J, Vreeling H,Meijer AJ, van Gulik TM. Improved machine perfusion preservation of the non-heart beating donor rat liver using Polysol: A new machine perfusion preservation solution. Liver Transplant 2005; 11: 1379–1388. Cerca con Google

-Upadhya GA, Strasberg SM. Glutathione, lactobionate, and histidine: Cryptic inhibitors of matrix metalloproteinases contained in University of Wisconsin and histidin/tryptophan/ketoglutarate liver preservation solutions. Hepatology 2000; 31: 1115–1122. Cerca con Google

-Kamada N, Calne R, Wight D, Lines J. Orthotopic rat liver transplantation after long-term preservation by continuous perfusion with fluorocarbon emulsion. Transplantation 1980; 30: 43–48. Cerca con Google

-Tamaki T, Kamada N, Wight D, Pegg D. Successful 48-hour preservation of the rat liver by continuous hypothermic perfusion with haemaccel-isotonic citrate solution. Transplantation 1987; 43: 468–471. Cerca con Google

- Dutkowski P, Krug A, Krysiak M, Dunschede F, Seifert JK, Junginger T. Detection of mitochondrial electron chain carrier redox status by transhepatic light intensity during rat liver reperfusion Cryobiology 2003; 47: 125–142. Cerca con Google

-Dutkowski P, Schonfeld S, Heinrich T et al. Reduced oxidative stress during acellular reperfusion of the rat liver after hypothermic oscillating perfusion. Transplantation 1999; 68: 44–50. Cerca con Google

-Minor T, Manekeller S, Sioutis M, Dombrowski F. Endoplasmic and vascular surface activation during organ preservation: Refining upon the benefits of machine perfusion. Am J Transplant 2006; 6:1355–1366. Cerca con Google

-Bailly-Maitre B, Fondevila C, Kaldas F et al. Cytoprotective gene bi-1 is required for intrinsic protection from endoplasmatic reticulum stress and ischemia reperfusion injury. Proc Natl Acad Sci USA 2006; 103: 2809–2814. Cerca con Google

-Lauschke H, Olschewski P, Tolba R, Schulz S, Minor T. Oxygenated machine perfusion mitigates surface antigen expression and improves preservation of predamaged donor livers. Cryobiology 2003; 46: 53–60. Cerca con Google

-Rauen U, Petrat F, Li T, de Groot HH. Hypothermia injury/cold induced apoptosis—evidence of an increase in chelatable iron causing oxidative injury in spite of low O2− / H2O2 formation. FASEB J 2000; 14: 1953–1964. Cerca con Google

-‘t Hart NA, van der Plaats A, Faber A et al. Oxygenation during hypothermic rat liver preservation: An in vitro slice study to demonstrate beneficial or toxic oxygenation effects. Liver Transplant 2005; 11: 1403–1411. Cerca con Google

-Bessems M, Doorschodt BM, Kolkert JL et al. Preservation of steatotic livers: A comparison between cold storage and machine perfusion preservation. Liver Transplant 2007; 13: 497–504. Cerca con Google

-Manekeller S, Dobberrahn V, Hirner A, Minor T. Liver integrity after warm ischemia in situ and brief preservation ex vivo: The value of aerobic postconditioning. Cryobiology 2007; 55: 249–254. Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record