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Cold Ischemia (cold + ischemia)

Distribution by Scientific Domains

Medical Sciences	100%

Kinds of Cold Ischemia

liver cold ischemia

Terms modified by Cold Ischemia

cold ischemia time

Selected Abstracts

Cytoprotective Effects of a Cyclic RGD Peptide in Steatotic Liver Cold Ischemia and Reperfusion Injury

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
C. Fondevila
The serious need for expanding the donor population has attracted attention to the use of steatotic donor livers in orthotopic liver transplantation (OLT). However, steatotic livers are highly susceptible to hepatic ischemia,reperfusion injury (IRI). Expression of fibronectin (FN) by endothelial cells is an important feature of hepatic response to injury. We report the effect of a cyclic RGD peptide with high affinity for the ,5,1, the FN integrin receptor, in a rat model of steatotic liver cold ischemia, followed by transplantation. RGD peptide therapy ameliorated steatotic IRI and improved the recipient survival rate. It significantly inhibited the recruitment of monocyte/macrophages and neutrophils, and depressed the expression of pro-inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and interferon (IFN)-,. Moreover, it resulted in profound inhibition of metalloproteinase-9 (MMP-9) expression, a gelatinase implied in leukocyte migration in damaged livers. Finally, we show that RGD peptide therapy reduced the expression of the 17-kDa active caspase-3 and the number of apoptotic cells in steatotic OLTs. The observed protection against steatotic liver IRI by the cyclic RGD peptides with high affinity for the ,5,1 integrin suggests that this integrin is a potential therapeutic target to allow the successful utilization of marginal steatotic livers in transplantation. [source]

Effect of Hepatic Artery Flow on Bile Secretory Function After Cold Ischemia

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2003
David P. Foley
These studies evaluated the influence of hepatic arterial flow on biliary secretion after cold ischemia. Preparation of livers for transplantation or hepatic support impairs biliary secretion. The earliest indication of cold preservation injury during reperfusion is circulatory function. Arterial flow at this time may be critical for bile secretion. Porcine livers were isolated, maintained at 4° for 2 h and connected in an extracorporeal circuit to an anesthetized normal pig. The extracorporeal livers were perfused either by both the hepatic artery and portal vein (dual) or by the portal vein alone (single). Incremental doses of sodium taurocholate were infused into the portal vein of both the dual and single perfused livers, and the bile secretion was compared. Most endogenous bile acids are lost during hepatic isolation. After supplementation, the biliary secretion of phosphatidyl choline and cholesterol was significantly better in the dual than single vessel-perfused livers; however, no difference was seen in bilirubin output. Single perfused livers were completely unable to increase biliary cholesterol in response to bile acid. The dependence of bile cholesterol secretion on arterial flow indicates the importance of this flow to the detoxification of compounds dependent on phosphatidyl choline transport during early transplantation. [source]

Biliverdin therapy protects rat livers from ischemia and reperfusion injury

HEPATOLOGY, Issue 6 2004
Constantino Fondevila
Heme oxygenase (HO-1) provides a cellular defense mechanism during oxidative stress and catalyzes the rate-limiting step in heme metabolism that produces biliverdin (BV). The role of BV and its potential use in preventing ischemia/reperfusion injury (IRI) had never been studied. This study was designed to explore putative cytoprotective functions of BV during hepatic IRI in rat liver models of ex vivo perfusion and orthotopic liver transplantation (OLT) after prolonged periods of cold ischemia. In an ex vivo hepatic IRI model, adjunctive BV improved portal venous blood flow, increased bile production, and decreased hepatocellular damage. These findings were correlated with amelioration of histological features of IRI, as assessed by Suzuki's criteria. Following cold ischemia and syngeneic OLT, BV therapy extended animal survival from 50% in untreated controls to 90% to 100%. This effect correlated with improved liver function and preserved hepatic architecture. Additionally, BV adjuvant after OLT decreased endothelial expression of cellular adhesion molecules (P-selectin and intracellular adhesion molecule 1), and decreased the extent of infiltration by neutrophils and inflammatory macrophages. BV also inhibited expression of inducible nitric oxide synthase and proinflammatory cytokines (interleukin 1,, tumor necrosis factor ,, and interleukin 6) in OLTs. Finally, BV therapy promoted an increased expression of antiapoptotic molecules independently of HO-1 expression, consistent with BV being an important mediator through which HO-1 prevents cell death. In conclusion, this study documents and dissects potent cytoprotective effects of BV in well-established rat models of hepatic IRI. Our results provide the rationale for a novel therapeutic approach using BV to maximize the function and thus the availability of donor organs. (HEPATOLOGY 2004;40:1333,1341.) [source]

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

HEPATOLOGY, Issue 6 2000
Olivier Le Moine M.D.
Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-,) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemia-reperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-, were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-, release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-, release (,66% or ,41%, ,95% or ,94%, and ,70% or ,70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell, and macrophage-dependent cytokines. [source]

Auto-transplantation of the uterus in the domestic pig (Sus scrofa): Surgical technique and early reperfusion events

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2006
Caiza Almén Wranning
Abstract Aim:, To develop a method for auto-transplantation of the uterus in the pig and to evaluate the early reperfusion events after short-term cold ischemia. Methods:, The bicornate uterus, with the cervix but without ovaries, was dissected and isolated with its bilateral feeding and draining vessels. The uterine arteries were cannulated in situ and the uterus was flushed with heparinized Ringer Acetate. It was stored at 4°C for 1,2 h during continuous flushing. The uterus was then placed in its original pelvic position and the uterine arteries and veins were anastomosed end-to-end to their origin. During approximately 100 min of reperfusion, blood samples and tissue biopsies were taken for monitoring of reperfusion events and detection of ischemia-reperfusion injuries. Results:, Out of 19 auto-transplanted pigs, seven were considered well flushed and were kept for cold ischemia. Of these seven, four showed satisfactory reperfusion judged by change in gross appearance and presence of appropriate venous blood flow. Analysis of blood-gas and metabolite parameters and histology indicated that at least two of these transplants were well reperfused, with no severe ischemia-reperfusion injuries. Conclusion:, In this first report ever on auto-transplantation of the pig uterus it is demonstrated that an acceptable reperfusion can be achieved. Furthermore, it is suggested that because of the large total size of the pig uterus with long uterine horns and the small size of the vessels available for re-anastomosis, the pig is a fairly difficult model for further studies on transplantation of the uterus. [source]

Rapamycin inhibits cholangiocyte regeneration by blocking interleukin-6,induced activation of signal transducer and activator of transcription 3 after liver transplantation

LIVER TRANSPLANTATION, Issue 2 2010
Li-Ping Chen
Cholangiocyte proliferation is necessary for biliary recovery from cold ischemia and reperfusion injury (CIRI), but there are few studies on its intracellular mechanism. In this process, the role of rapamycin, a new immunosuppressant used in liver transplantation, is still unknown. In order to determine whether rapamycin can depress cholangiocyte regeneration by inhibiting signal transducer and activator of transcription 3 (STAT3) activation, rapamycin (0.05 mg/kg) was administered to rats for 3 days before orthotopic liver transplantation. The results indicated that cholangiocytes responded to extended cold preservation (12 hours) with severe bile duct injures, marked activation of the interleukin-6 (IL-6)/STAT3 signal pathway, and increased expression of cyclin D1 until 7 days after transplantation, and this was followed by compensatory cholangiocyte regeneration. However, rapamycin treatment inhibited STAT3 activation and resulted in decreased cholangiocyte proliferation and delayed biliary recovery after liver transplantation. On the other hand, rapamycin showed no effect on the expression of IL-6. We conclude that the IL-6/STAT3 signal pathway is involved in initiating cholangiocytes to regenerate and repair CIRI. Rapamycin represses cholangiocyte regeneration by inhibiting STAT3 activation, which might have a negative effect on the healing and recovery of bile ducts in grafts with extended cold preservation. Insights gained from this study will be helpful in designing therapy using rapamycin in clinical patients after liver transplantation. Liver Transpl, 2010. © 2010 AASLD. [source]

Postreperfusion syndrome during liver transplantation for cirrhosis: Outcome and predictors

LIVER TRANSPLANTATION, Issue 5 2009
Catherine Paugam-Burtz
During orthotopic liver transplantation (OLT), a marked decrease in blood pressure following unclamping of the portal vein and liver reperfusion is frequently observed and is termed postreperfusion syndrome (PRS). The predictive factors and clinical consequences of PRS are not fully understood. The goal of this study was to identify predictors of PRS and morbidity/mortality associated with its occurrence during OLT in patients with cirrhosis. During a 3-year period, all consecutive OLT procedures performed in patients with cirrhosis were studied. Exclusion criteria were OLT for acute liver failure, early retransplantation, combined liver/kidney transplantation, and living-donor related transplantation. PRS was defined as a decrease in the mean arterial pressure of more than 30% of the value observed in the anhepatic stage, for more than 1 minute during the first 5 minutes after reperfusion of the graft. Transplantation was performed with preservation of the inferior vena cava with or without temporary portocaval shunt. Associations between PRS and donor and recipient demographic data, recipient operative and postoperative outcomes were tested with bivariate statistics. Independent predictors of PRS were determined in multivariable logistic regression analysis. Of the 75 patients included in the study, 20 patients (25%) developed PRS. In a multivariable analysis, absence of a portocaval shunt [odds ratio (95% confidence interval) = 4.42 (1.18-17.6)] and duration of cold ischemia [odds ratio (95% confidence interval) = 1.34 (1.07-1.72)] were independent predictors of PRS. Patients who experienced PRS displayed more postoperative renal failure and lower early (<15 days after OLT) survival (80% versus 96%; P = 0.04). In conclusion, the absence of portocaval shunt and the duration of cold ischemia were independent predictors of intraoperative PRS. PRS was associated with significant adverse postoperative outcome. These results provide realistic clinical targets to improve patient outcome after OLT for cirrhosis. Liver Transpl 15:522,529, 2009. © 2009 AASLD. [source]

The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury

LIVER TRANSPLANTATION, Issue 8 2008
Constantino Fondevila
Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(,) rats were harvested, stored for 24 hours at 4°C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+),C6(+), (2) C6(+),C6(,), (3) C6(,),C6(+), and (4) C6(,),C6(,). At day +1, C6(,) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 ± 0.9, 7.3 ± 1.3, 4.5 ± 0.6, and 4.8 ± 0.4 for groups 1-4, respectively, P < 0.05). The liver function improved in recipients of C6(,) grafts (serum glutamic oxaloacetic transaminase: 2573 ± 488, 1808 ± 302, 1170 ± 111, and 1188 ± 184 in groups 1-4, respectively, P < 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(,) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-,, interleukin-1,, and tumor necrosis factor messenger RNA/protein was also reduced in C6(,) OLTs in comparison with C6(+) OLTs. Western blot,assisted expression of proapoptotic caspase-3 was decreased in C6(,) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(,) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase,mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(,) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients. Liver Transpl 14:1133,1141, 2008. © 2008 AASLD. [source]

A caspase inhibitor, IDN-6556, ameliorates early hepatic injury in an ex vivo rat model of warm and cold ischemia,

LIVER TRANSPLANTATION, Issue 3 2007
Niel C. Hoglen
This study examined the efficacy of the caspase inhibitor, IDN-6556, in a rat model of liver ischemia-reperfusion injury. Livers from male Sprague-Dawley rats were reperfused for 120 minutes after 24 hours of 4°C cold storage in University of Wisconsin solution. Portal blood flow measurements estimated sinusoidal resistance, and bile production, alanine aminotransferase activities, and Suzuki scores were evaluated as parameters of hepatocyte/liver injury. Treated livers were exposed to 25 or 50 ,M of IDN-6556 in University of Wisconsin storage solution and/or the perfusate. All treatment regimens with IDN-6556 significantly improved portal blood flow measured at 120 minutes, and significant improvements were seen as early as 30 minutes when inhibitor was also present in the perfusate (P < 0.01). All treatment groups with IDN-6556 significantly increased bile production by 3-4-fold compared with controls (P < 0.01), and reductions in alanine aminotransferase activities were seen within 90 minutes of reperfusion (P < 0.05). These data were confirmed by improved Suzuki scores (less sinusoidal congestion, necrosis, and vacuolization) in all treated groups. Livers from the IDN-6556,treated groups had markedly reduced caspase activities and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-positive cells, suggesting reductions in apoptosis. IDN-6556 present in cold storage media ameliorated liver injury due to cold ischemia and reperfusion injury and may be a rational therapeutic approach to reduce the risk of liver ischemia in the clinical setting. Liver Transpl 13: 361,366, 2007. © 2007 AASLD. [source]

Mediators of rat ischemic hepatic preconditioning after cold preservation identified by microarray analysis

LIVER TRANSPLANTATION, Issue 11 2006
Àurea Navarro-Sabaté
Hepatic ischemia-reperfusion injury associated with liver transplantation is an as yet unresolved problem in clinical practice. Preconditioning protects the liver against the deleterious effects of ischemia, although the mechanism underlying this preconditioning is still unclear. To profile gene expression patterns involved in hepatic ischemic preconditioning, we analyzed the changes in gene expression in rat livers by DNA microarray analysis. Approximately 116 genes were found to have altered gene expression after 8 hours of cold ischemia. Moreover, the expression of 218 genes was modified by classic preconditioning followed by the same ischemia process. Given the importance of the effects of ischemic preconditioning (IP) in minimizing the liver damage induced by sustained ischemia before reperfusion, this study analyzed the putative genes involved in the beneficial role of IP in liver grafts undergoing cold ischemia before its implantation in the recipient (IP+I). Great differences were found in the gene expression pattern of ischemic preconditioning + long cold ischemia (IP+I) group when compared with the long cold ischemia alone condition (I), which could explain the protective regulatory mechanisms that take place after preconditioning. Twenty-six genes that were downregulated in cold ischemia were found upregulated after preconditioning preceding a long cold ischemia period. These would be genes activated or maintained by preconditioning. Heat shock protein genes and 3-hydroxy-3-methylglutaryl-coenzyme A reductase are among the most markedly induced transcripts. Liver Transpl. 12:1615,1625, 2006. © 2006 AASLD. [source]

Small-for-size liver syndrome after auxiliary and split liver transplantation: Donor selection

LIVER TRANSPLANTATION, Issue 9 2003
Nigel Heaton
Small-for-size liver grafts can be defined by a recognizable clinical syndrome that results from the transplantation of too small a functional mass of liver for a designated recipient. A graft to recipient body weight ratio less than 0.8, impaired venous inflow, and enhanced metabolic demands in patients with poor clinical conditions must be considered as main factors leading to the small-for-size syndrome (SFSS) when using living and cadaveric partial grafts such as split and auxiliary liver grafts. Increased risk of graft dysfunction is currently observed in fatty infiltration of more than 30%, abnormal liver test results (especially bilirubin and gamma glutaryl transferase), and other donor risk factors such as high inotrope administration and donor stay in the intensive care unit (>5 days). Older donors are especially vulnerable to prolonged cold ischemia and high inotrope levels, giving rise to early graft dysfunction and prolonged cholestasis. Increased metabolic need on a functionally small-for-size graft predisposes to surgical and septic complications and poorer survival. Splitting livers into right and left lobe grafts increases the potential risk of small-for-size grafts for both recipients. Several techniques of venous outflow reconstruction/implantation have been proposed to reduce the risk of obstruction postoperatively. Prevention and management of SFSS will improve in parallel with the increased experience, allowing us optimum usage of available organs and reducing overall morbidity and mortality. (Liver Transpl 2003;9:S26-S28.) [source]

Interspecies differences in hepatic Ca2+ -ATPase activity and the effect of cold preservation on porcine liver Ca2+ -ATPase function

LIVER TRANSPLANTATION, Issue 2 2001
Piotr K. Janicki MD
The accumulation of intracellular calcium ([Ca2+]i) caused by ischemia-reperfusion during liver transplantation has been implicated as a factor leading to primary graft nonfunction. Plasma membrane (PM) and endoplasmic reticulum (ER) Ca2+ -adenosinetriphosphatases (ATPases) are the primary transporters that maintain [Ca2+]i homeostasis in the liver. We hypothesized that the porcine liver is better than the rat liver as a model for the study of human liver Ca2+ -ATPase activity. We also hypothesized that cold preservation would depress Ca2+ -ATPase activity in the porcine liver. Pig and rat livers were harvested, and human liver samples were obtained from surgical resection specimens. All were preserved with University of Wisconsin solution, and porcine livers were also preserved on ice for 2 to 18 hours. Ca2+ -ATPase activity was measured after incubation with 45Ca2+ and adenosine triphosphate in the presence of specific Ca2+ -ATPase inhibitors. Porcine PM and ER Ca2+ -ATPase activities were 0.47 ± 0.03 and 1.57 ± 0.10 nmol of Ca2+/mg of protein/min, respectively. This was not significantly different from human liver, whereas rat liver was significantly greater at 2.60 ± 0.03 and 9.2 ± 0.9 nmol of Ca2+/mg of protein/min, respectively. We conclude that the Ca2+ -ATPase activity in the pig liver is equivalent to that of human liver, and thus, the pig liver is a better model than the rat liver. Cold preservation studies showed a significant decrease in porcine hepatic PM Ca2+ -ATPase activity after 4 hours of storage and near-total inhibition after 12 hours. Porcine hepatic ER Ca2+ -ATPase activity showed a 45% decrease in activity by 12 hours and a 69% decrease by 18 hours. We conclude that cold ischemia at clinically relevant times depresses PM Ca2+ -ATPase more than ER Ca2+ -ATPase activity in pig liver homogenates. [source]

Kinetics of PME/Pi in pig kidneys during cold ischemia

NMR IN BIOMEDICINE, Issue 7 2007
Dominik von Elverfeldt
Abstract Quality assessment of renal grafts via 31P magnetic resonance spectroscopy (MRS) has been investigated since 1986. As ATP concentrations decay rapidly during cold ischemia, the ratio of phosphomonoesters (PME) to inorganic phosphate (PiO) within the organ (PME/PiO) is commonly used as a quality marker and is considered to be the most reliable parameter. MRS did not lead to any delay in the transplantation procedure since it was performed during the time necessary for immunological matching (cross-match). Differences in the time period until transplantation call for extrapolation of the measured ratio to the end of cold ischemia before correlating with graft performance after transplantation. Therefore, quantitative determination of PME/PiO kinetics is essential. As a model for metabolite decay in human renal grafts, pig kidneys obtained from a slaughterhouse were monitored for up to 80,h via 31P MRS at 2,T. By employing chemical shift imaging (CSI) with a spatial resolution of approximately 1,×,1,×,4,cm3, it was possible to reduce partial volume effects significantly. The improved spectral resolution gained through CSI enabled reliable PME/PiO ratios to be determined only from those voxels containing renal tissue. Spectra were fitted automatically using the magnetic resonance user interface (MRUI), with prior knowledge obtained from unlocalized spectra when necessary. A monoexponential time dependence of PME/PiO for histidine,tryptophane,alpha-ketoglutarate (HTK)-perfused kidneys during cold ischemia was observed, and the determined value of the decay constant , was 0.0099,±,0.0012,h,1. In University of Wisconsin solution (UW)-perfused kidneys, an , of 0.0183,±,0.0053,h,1 was determined. Determination of the decay constant enables a usable extrapolation of PME/PiO for quality assessment of UW perfusion and a reliable extrapolation for HTK-perfused human renal grafts. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Operative Start Times and Complications After Liver Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010
B. E. Lonze
The recent national focus on patient safety has led to a re-examination of the risks and benefits of nighttime surgery. In liver transplantation, the hypothetical risks of nighttime operation must be weighed against either the well-established risks of prolonging cold ischemia or the potential risks of strategies to manipulate operative start times. A retrospective review was conducted of 578 liver transplants performed at a single institution between 1995 and 2008 to determine whether the incidence of postoperative complications correlated with operative start times. We hypothesized that no correlation would be observed between complication rates and operative start times. No consistent trends in relative risk of postoperative wound, vascular, biliary, or other complications were observed when eight 3-h time strata were compared. When two 12-h time strata (night, 3 p.m.,3 a.m., and day, 3 a.m.,3 p.m.) were compared, complications were not significantly different, but nighttime operations were longer in duration, and were associated a twofold greater risk of early death compared to daytime operations (adjusted OR 2.9, 95% CI 1.16,7.00, p = 0.023), though long-term survival did not differ significantly between the subgroups. This observation warrants further evaluation and underscores the need to explore and identify institution-specific practices that ensure safe operations regardless of time of day. [source]

Cytoprotective Effects of a Cyclic RGD Peptide in Steatotic Liver Cold Ischemia and Reperfusion Injury

Survival Outcomes Following Liver Transplantation (SOFT) Score: A Novel Method to Predict Patient Survival Following Liver Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2008
A. Rana
It is critical to balance waitlist mortality against posttransplant mortality. Our objective was to devise a scoring system that predicts recipient survival at 3 months following liver transplantation to complement MELD-predicted waitlist mortality. Univariate and multivariate analysis on 21 673 liver transplant recipients identified independent recipient and donor risk factors for posttransplant mortality. A retrospective analysis conducted on 30 321 waitlisted candidates reevaluated the predictive ability of the Model for End-Stage Liver Disease (MELD) score. We identified 13 recipient factors, 4 donor factors and 2 operative factors (warm and cold ischemia) as significant predictors of recipient mortality following liver transplantation at 3 months. The Survival Outcomes Following Liver Transplant (SOFT) Score utilized 18 risk factors (excluding warm ischemia) to successfully predict 3-month recipient survival following liver transplantation. This analysis represents a study of waitlisted candidates and transplant recipients of liver allografts after the MELD score was implemented. Unlike MELD, the SOFT score can accurately predict 3-month survival following liver transplantation. The most significant risk factors were previous transplantation and life support pretransplant. The SOFT score can help clinicians determine in real time which candidates should be transplanted with which allografts. Combined with MELD, SOFT can better quantify survival benefit for individual transplant procedures. [source]

Resident Macrophages are Involved in Intestinal Transplantation-Associated Inflammation and Motoric Dysfunction of the Graft Muscularis

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007
N. Schaefer
Gut manipulation and ischemia/reperfusion evoke an inflammatory response within the intestinal muscularis that contributes to dysmotility. We hypothesize that resident macrophages play a key role in initiating the inflammatory cascade. Isogenic small bowel transplantation was performed in Lewis rats. The impact of recovery of organs on muscularis inflammation was investigated by comparing cold whole-body perfusion after versus prior to recovery. The role of macrophages was investigated by transplantation of macrophage-depleted gut. Leukocytes were counted using muscularis whole mounts. Mediator expression was determined by real-time RT-PCR. Contractility was assessed in a standard organ bath. Both organ recovery and ischemia/reperfusion induced leukocyte recruitment and a significant upregulation in IL-6, MCP-1, ICAM-1 and iNOS mRNAs. Although organ recovery in cold ischemia prevented early gene expression, peak expression was not changed by modification of the recovery technique. Compared to controls, transplanted animals showed a 65% decrease in smooth muscle contractility. In contrast, transplanted macrophage-depleted isografts exhibited significant less leukocyte infiltration and only a 19% decrease in contractile activity. In summary, intestinal manipulation during recovery of organs initiates a functionally relevant inflammatory response within the intestinal muscularis that is massively intensified by the ischemia reperfusion injury. Resident muscularis macrophages participate in initiating this inflammatory response. [source]