Precondicionamiento isquémico es una estrategia quirúrgica útil en el trasplante hepático con injerto de tamaño reducido, El

[spa] El trasplante hepático es la solución para personas que sufren enfermedades hepática terminales o insuficiencia hepática aguda. La principal limitación para la aplicación del trasplante es la falta de órganos respecto a la demanda. El trasplante hepático con injerto de tamaño reducido se desarrolló para aumentar el número de órganos disponibles y así disminuir la lista de espera. Además del síndrome de isquemia/reperfusión (I/R) asociado al proceso de trasplante, es necesario un proceso de regeneración para la viabilidad del injerto. El síndrome de I/R también tiene efectos sistémicos nocivos en el pulmón. El precondicionamiento isquémico (PC) es una estrategia quirúrgica útil frente a la lesión por I/R en modelos de I/R normotérmica y trasplante hepático con 8 y 16 horas de isquemia, con buenos resultados en la clínica, en resección de tumores, pero se desconoce su efecto en el modelo de trasplante hepático con injerto de tamaño reducido en la rata. En la presente tesis se ha demostrado que el PC es una estrategia útil frente a la lesión por I/R y que favorece la regeneración asociada al modelo de trasplante hepático de tamaño reducido en la rata, modulando factores de crecimiento, como el factor de crecimiento hepatocitario (HGF) y el factor de crecimiento transformante-beta (TGF-beta), modulando la producción de radicales libres (RLO) (por parte de las células de kupffer) y todo esto cursa a través de la disminución de la IL-alfa y con una implicación del óxido nítrico (NO). Sin embargo, el PC no ejerce su papel protector mediante cambios en el sistema productor de RLO xantina/xantina oxidasa, cambios en los niveles de las citoquinas TNF-alfa y IL-6, ni mediante la preservación del metabolismo energético. Por otra vía independiente del NO, el PC estimula la expresión de la Heat shock protein (HSP) 70 y HO-1, estimulando la regeneración en el caso de la HSP70 y disminuyendo la lesión y estimulando la regeneración en el caso de la HO-1. Por otro lado, el PC fue capaz de conferir protección a nivel pulmonar, así la disminución de la IL-1alfa se tradujo en una disminución en los niveles de TNF-alfa plasmáticos y un aumento del receptor soluble de TNF-alfa de tipo 2 (sTNFR2), que es capaz de inactivar el TNF-alfa libre en la circulación sanguínea, evitando los efectos nocivos del TNF-alfa a nivel pulmonar.[eng] Reduced-size liver transplantation (RSLT) was developed to arise the number of available liver grafts In addition to ischemia/reperfusion (I/R) injury associated to liver transplantation, the reduced grafts have to overcome a necessary regeneration process. I/R injury has deleterious systemic effects, leading to pulmonary complications. Ischemic preconditioning (IP) is able to protect liver against I/R injury and lung damage in conventional rat liver transplantation. Recently, has been published its clinical application in tumour resections. In the present thesis work, it has been demonstrated the IP is able to reduce I/R injury and stimulate regeneration associated to RSLT. IP modulated growth factors, as hepatocyte growth factor and transforming growth factor-beta and the stress oxidative production, and it was related to the reduction of IL-1alpha levels . Nitric oxide (NO) was implicated in the benefits of IP. However, PC has not any effect on xanthine/xanthine oxidase system, neither on IL-6 and TNF-alpha levels and energetic metabolism. By another pathway independent of NO, IP induced heat shock protein 70 (HSP70) and haem-oxygenase-1 (HO-1). HO-1 protected against I/R injury and liver regeneration, whereas the benefits resulting from HSP70 were mainly related to hepatocyte proliferation. On the other hand, IP was able to confer lung protection. In this line, reduction of IL.-1alpha levels was associated with lower TNF-alpha and higher soluble receptor TNF-alpha type 2 (sTNFR2) plasma levels

Kibble-Zurek Dynamics in a Trapped Ultracold Bose Gas

The dynamical evolution of an inhomogeneous ultracold atomic gas quenched at different controllable rates through the Bose-Einstein condensation phase transition is studied numerically in the premise of a recent experiment in an anisotropic harmonic trap. Our findings based on the stochastic (projected) Gross-Pitaevskii equation are shown to be consistent at early times with the predictions of the homogeneous Kibble-Zurek mechanism. This is demonstrated by collapsing the early dynamical evolution of densities, spectral functions and correlation lengths for different quench rates, based on an appropriate characterization of the distance to criticality felt by the quenched system. The subsequent long-time evolution, beyond the identified dynamical critical region, is also investigated by looking at the behaviour of the density wavefront evolution and the corresponding phase ordering dynamics

IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver transplantation

Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality

Ischemia-reperfusion syndrome associated with liver transplantation: An update

Ischemia-reperfusion (I/R) injury is the main cause of both initial graft dysfunction and primary failure in liver transplantation. The search for therapeutic strategies to prevent I/R injury has led to research into promising drugs, although most have not been used clinically. Gene therapy requires better transfection techniques, avoiding vector toxicity, and ethical debate before being used clinically. Ischemic preconditioning is the first therapeutic strategy used in clinical practice to reduce I/R injury in hepatectomies for tumors. Future research will provide data on the effectiveness of ischemic preconditioning in reducing I/R injury associated with liver transplantation, and in reducing the vulnerability of steatotic grafts to I/R syndrome so that they can be used in transplantation, thus relieving the organ shortage.Peer Reviewe

New preservation strategies for preventing liver grafts against cold ischemia reperfusion injury

[Background]: In spite of improvements in University of Wisconsin (UW) preservation solution, the injury from grafts during cold storage is an unresolved problem in liver transplantation. The aim of the present study was to evaluate the beneficial effect on ischemia-reperfusion injury associated with liver transplantation of the inversion of K+ and Na+ concentrations and the replacement of hydroxyethyl starch (HES) by polyethylene glycol (PEG) in UW preservation solution. [Methods]: Using an orthotopic liver transplantation model, the effects on rat liver preservation of a modified preservation solution (UW-PEG) were evaluated, based on the inversion of K+ and Na+ concentration and the replacement of HES by PEG 35 kDa (0.03 mmol/L) in UW preservation solution. [Results]: The use of UW-PEG preservation solution ameliorated the biochemical and histological parameters of hepatic damage. Thus, at 24 h after transplantation, transaminase levels were reduced significantly when livers were preserved during 8 h in UW-PEG preservation solution compared with the original UW solution. In addition, histological findings revealed fewer and smaller areas of hepatocyte necrosis. The benefits of UW-PEG solution cannot be explained by modifications in oxidative stress or neutrophil accumulation associated with liver transplantation. However, the results of hepatic and portal blood flow indicated that the benefits of this modified preservation solution, UW-PEG were associated with improvements in the microcirculatory disorders after reperfusion. [Conclusions]: The UW-PEG solution, while retaining all the advantages of UW solution, improved hepatic ischemia-reperfusion injury associated with liver transplantation. © 2006 The Authors.This study was supported by the Ministerio de Ciencia y Tecnología (project grants SAF 2005-00385 and BFI 2003-00912, and Ramón y Cajal research contract to Carmen Peralta), the Minsterio de Asuntos Exteriores y Cooperación/Agencia Española de Cooperación Internacional (A4251/05 and CN0012/2002 research projects) and the Generalitat de Catalunya (2005 SGR/00781) I. Ben Mosbah holds a fellowship from the AECI.Peer Reviewe

Critical Care Management of the Liver Transplant Recipient

Liver transplantation is an acceptable treatment modality for complications of end-stage liver disease from chronic and acute liver failure. In the United States, 16 377 people are currently awaiting liver transplant but only 6492 transplantations were performed in 2007. All options for liver transplantation including Model for End stage Liver Disease allocated, expanded criteria deceased donors, and live donor liver transplantation should be discussed with potential recipients on the waitlist to create an early access plan for safe and expeditious transplantation. After transplantation, careful management to avoid complications and intervene early is necessary. Common postoperative complications include graft dysfunction, vascular thrombosis, biliary tract complications, infection, rejection, neurologic injury, electrolyte imbalances, and drug interactions. A multidisciplinary approach to care including the critical care nurse is necessary for successful long-term outcomes

How ischaemic preconditioning protects small liver grafts

Interleukin-1 (IL-1) and transforming growth factor-β (TGFβ) are key inhibitors of hepatocyte proliferation after hepatectomy. IL-1 inhibition by heat shock proteins (HSPs) has been reported in inflammatory processes. A recent study indicated the benefits of ischaemic preconditioning in reduced-size orthotopic liver transplantation (ROLT). The present study examined: (a) the effect of ischaemic preconditioning on IL-1 and TGFβ in ROLT; (b) whether preconditioning protects small liver grafts through HSP induction; and (c) whether the potential benefits of preconditioning on HSP is related to IL-1 inhibition. Our results, obtained with an IL-1 receptor antagonist, indicated the injurious effects of IL-1 in ischaemia-reperfusion (I/R) injury and established a relationship between IL-1 and growth factors. Thus, IL-1 reduced hepatocyte growth factor (HGF) and promoted TGFβ release, thus contributing to the impaired liver regeneration associated with ROLT. Preconditioning inhibited IL-1 through nitric oxide (NO), thereby protecting against the injurious effects of IL-1. In addition, by another pathway independent of NO, preconditioning induced HSP70 and haem-oxygenase-1 (HO-1). HO-1 protected against I/R injury and liver regeneration, whereas the benefits resulting from HSP70 were mainly related to hepatocyte proliferation. These results suggest a mechanism that explains the effectiveness of preconditioning in ROLT. They suggest, too, that other strategies, in addition to preconditioning, that modulate IL-1 and/or HSPs could be considered in clinical situations requiring liver regeneration such as small liver grafts. Copyright © 2005 Pathological Society of Great Britain and Ireland.This work was supported by the Ministerio de Ciencia y Tecnología (project grants BFI 2002-00704 and BFI 2003-00912 and Ramón y Cajal research contract for Carmen Peralta), the Ministerio de Sanidad y Consumo (project grant V2003-REDC03G-O) (Madrid, Spain) and Fundació Marató TV3Peer Reviewe

Preservation of steatotic livers in IGL-1 solution

A new Institut Georges Lopez (IGL-1) solution was used to preserve steatotic livers. Steatotic (obese [Ob]) and nonsteatotic (lean [Ln]) livers from Zücker rats (n = 16, 8 Ln and 8 Ob) were preserved for 24 hours at 4°C in University of Wisconsin (UW) or IGL-1 solution, respectively, and then perfused ex vivo for 2 hours at 37°C. Additionally, Ob and Ln livers (n = 16, 8 Ln and 8 Ob) were preserved in IGL-1 plus Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Hepatic injury and function (aminotransferases, bile production, bromosulfophthalein clearance), and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion injury, such as oxidative stress, mitochondrial damage, and vascular resistance, were studied. Nitric oxide (NO) production and constitutive and inducible NO synthase were also measured. Steatotic and nonsteatotic livers preserved in IGL-1 solution showed lower transaminases, malondialdehyde, glutamate dehydrogenase levels, and higher bile production than UW-solution-preserved livers. IGL-1 solution protected against oxidative stress, mitochondrial damage and the alterations in vascular resistance associated with cold ischemia-reperfusion. Thus, at the end of reperfusion period, aspartate aminotransferase levels in steatotic livers were 281 ± 6 U/L in UW vs. 202 ± 10 U/L in IGL-1 solution. Glutamate dehydrogenase was 463 ± 75 U/L in UW vs. 111 ± 4 U/L in IGL-1 solution, and oxidative stress was 3.0 ± 0.1 nmol/mg prot in UW vs. 2.0 ± 0.1 nmol/mg prot in IGL-1 solution. These beneficial effects of IGL-1 solution were abolished by the addition of L-NAME, which implicates NO in the benefits of IGL-1. In conclusion, IGL-1 solution provided steatotic livers with better protection against the deleterious effects of cold ischemia-reperfusion injury than did UW solution. © 2006 AASLD.Peer Reviewe