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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver transplantation, a definitive treatment for end-stage liver disease, has achieved excellent results. However, potential recipients on the waiting list outnumber donors. To expand the donor pool, marginal grafts from older donors, steatotic livers, and non-heart-beating liver donors (NHBD) have been used for transplantation. Reducing the warm ischemia time of NHBD is the critical factor in organs preservation. Liver transplantation using grafts from NHBD have been reported to display a high incidence of primary graft nonfunction and biliary complications. The authors report a liver graft donor who was maintained on extracorporeal membrane oxygenation (ECMO) after successful cardiopulmonary resuscitation. Core body temperature was 5 degrees C. Procurement of the liver using a rapid flush technique was performed 4 hours after instituting ECMO. Graft function recovered fully after transplantation. In conclusion, ECMO may be used to reduce warm ischemia time in liver grafts obtained from uncontrolled NHBD, thereby increasing graft salvage rates.
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PMID:Liver transplantation from an uncontrolled non-heart-beating donor maintained on extracorporeal membrane oxygenation. 1638 12

Death of hepatocytes and other hepatic cell types is a characteristic feature of liver diseases as diverse as cholestasis, viral hepatitis, ischemia/reperfusion, liver preservation for transplantation and drug/toxicant-induced injury. Cell death typically follows one of two patterns: oncotic necrosis and apoptosis. Necrosis is typically the consequence of acute metabolic perturbation with ATP depletion as occurs in ischemia/reperfusion and acute drug-induced hepatotoxicity. Apoptosis, in contrast, represents the execution of an ATP-dependent death program often initiated by death ligand/death receptor interactions, such as Fas ligand with Fas, which leads to a caspase activation cascade. A common event leading to both apoptosis and necrosis is mitochondrial permeabilization and dysfunction, although the mechanistic basis of mitochondrial injury may vary in different settings. Prevention of these modes of cell death is an important target of therapy, but controversies still exist regarding which mode of cell death predominates in various forms of liver disease and injury. Resolution of these controversies may come with the recognition that apoptosis and necrosis frequently represent alternate outcomes of the same cellular pathways to cell death, especially for cell death mediated by mitochondrial permeabilization. An understanding of processes leading to liver cell death will be important for development of effective interventions to prevent hepatocellular death leading to liver failure and to promote cancer and stellate cell death in malignancy and fibrotic disease.
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PMID:Apoptosis and necrosis in the liver: a tale of two deaths? 1644 72

During the last decade, hepatocyte transplantation has been suggested as a safe and potentially effective clinical option for the treatment of acute or decompensating chronic liver failure as well as for hereditary liver disease. Currently, one of the major limiting factors for clinical application is the insufficient access to suitable liver cell preparations. In cooperation with the German and Catalane organ procurement organizations, a routine procedure for the isolation of hepatocytes from donor organs rejected for transplantation (n = 117) has been established. The process is performed according to the current EC Guidelines for Good Manufacturing Practice (cGMP) and all corresponding national laws and regulations concerning donor organ and tissue procurement. In about 50% of the cases (n = 58) the three-step perfusion procedure has been completed with an average total cell yield of 5.9 x 10(9) cells per organ, the cell preparations displaying a mean viability of 64%. The mean specific yield was 3.6 x 10(6) total and 2.6 x 10(6) viable cells per gram liver tissue, respectively. Specific cell yields from three infantile donor livers were considerably higher. No correlation between isolation efficiency and cold ischemia time or donor age was found within the adult organ donors. In contrast, organs with a severe steatosis generally did not result in successful cell isolation. Results of sterility and endotoxin determination are also presented. In summary, a standardized and cGMP conform method of hepatocyte isolation from nontransplantable liver organs was established, which reproducibly yields large amounts of hepatocytes suitable for therapeutic application.
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PMID:Large-scale isolation of human hepatocytes for therapeutic application. 1645 59

In Canada and Europe, yttrium-90 microspheres (TheraSphere); MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.
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PMID:Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere): assessment of hepatic arterial embolization. 1672 28

Although renal dysfunction is common after liver transplantation, postoperative renal function after split liver transplantation (SLT) has not been well studied. Renal function immediately after surgery was analyzed retrospectively in 16 patients that received a SLT (SLT group). The results were compared with corresponding data from 31 matched patients that received a full-size liver transplant (FSLT group) during the same period. Serum creatinine (SCr) was measured before surgery, and, after transplantation, daily during the first week and at days 14, 21, and 28. Renal dysfunction (RD) was defined as the requirement for renal replacement therapy (RRT) or a 100% increase in SCr if the basal value had been <1.0 mg/dL or a 50% increase in SCr if the basal value had been >1.0 mg/dL. SCr had to be at least 1.5 mg/dL for a diagnosis of RD to be considered. The classification of RD was: mild, SCr 1.5-2.4 mg/dL; moderate, SCr 2.5-4.0 mg/dL; or severe, SCr >4.0 mg/dL (the requirement for RRT). Both donor and recipient age and cold ischemia time were lower in the SLT group than in the FSLT group (P < 0.05). Length of surgery was longer in the SLT group (P < 0.05). There were no significant differences between groups with respect to Model for End-Stage Liver Disease scores, the need for transfusions, the length of admission to the intensive care unit (ICU), survival rate, individual severity index, or sepsis-related organ failure assessment scores at the time of diagnosing RD. Immunosuppression regimens were similar in both groups. RD developed in 82% of SLT patients, but in only 58% of FSLT patients (P = not significant [NS]). Among SLT patients, RD (23.0% mild, 15.5% moderate, and 61.5% severe) was more severe (P = 0.007) than in FSLT patients (63.1% mild, 15.8% moderate, and 24.1% severe). The requirement for RRT in the SLT group (43.7%) was significantly greater (P < 0.05) than that in the FSLT group (12.9%). This finding may be due to the different incidence of sepsis in the 2 groups (SLT 37.5% vs. FSLT 9.7%; P < 0.05). In conclusion, although the number of patients studied was small, our data suggest a higher incidence of RD and a greater requirement for RRT in patients that receive a split liver graft than in those that receive a full size liver graft.
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PMID:Analysis of renal function in the immediate postoperative period after partial liver transplantation. 1683 92

Liver resection and liver transplantation have been successful in the treatment of liver tumors and end-stage liver disease. This success has led to an expansion in the pool of patients potentially treatable by liver surgery and, in the case of transplantation, to a shortage of liver donors. At present, there are significant numbers of potential candidates for liver resection and liver donation who have fatty livers, are aged, or have livers damaged by chemotherapy. All of these are at high risk for ischemic reperfusion (IR) injury. The aims of this review are to assess current knowledge of the clinical effectiveness of ischemic preconditioning and intermittent ischemia in reducing IR damage in liver surgery; to evaluate the use of bile flow as a sensitive indicator of IR liver damage; and to analyze the molecular mechanisms, especially intracellular Ca2+, involved in IR injury and ischemic preconditioning. It is concluded that bile flow is a sensitive indicator of IR injury. Together with reactive oxygen species (ROS) and other extracellular and intracellular signaling molecules, intracellular Ca2+ in hepatocytes plays a key role in the normal regulation of bile flow and in IR-induced injury and cell death. Ischemic preconditioning is an effective strategy to reduce IR injury but there is considerable scope for improvement, especially in patients with fatty and aged livers. The development of effective new strategies to reduce IR injury will depend on improved understanding of the molecular mechanisms involved, especially by gaining a better perspective of the relative importance of the various intrahepatocyte signaling pathways involved.
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PMID:Hepatic ischemia-reperfusion injury: roles of Ca2+ and other intracellular mediators of impaired bile flow and hepatocyte damage. 1686 76

In animals, the bone marrow (BM) is a source of liver-repopulating cells with therapeutic potential in case of tissue damage. However, the early response of human BM-derived stem cells (SC) to liver injury is still unknown. Here, we studied 24 patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease or hepatocellularcarcinoma, and 13 patients submitted to liver resection. The concentration of circulating BM-derived SC was determined by phenotypic analysis and clonogenic assays. Moreover, we assessed the serum level of inflammatory and tissue-specific cytokines. Reverse transcriptase-polymerase chain reaction and fluorescence-in situ hybridization were also used to characterize mobilized SC. At baseline, patients showed a significant lower concentration of circulating CD133(+), CD34(+) SC and clonogenic progenitors (colony-forming unit cells) than healthy controls. However, the time-course evaluation of peripheral blood cells after OLT demonstrated the significant early mobilization of multiple subsets of hematopoietic and endothelial stem/progenitor cells. Cytogenetic and molecular analyses of CD34(+) cells showed the host origin of mobilized SC and the expression of transcripts for GATA-4, cytokeratin 19, and alpha-fetoprotein hepatocyte markers. In contrast with OLT, only total circulating CD34(+) cells significantly increased after liver resection. Mobilization of BM cells after OLT or liver surgery was associated with increased serum levels of granulocyte-colony stimulating factor, interleukin-6, stem cell factor, hepatocyte growth factor, and vascular endothelial growth factor. In summary, we demonstrate that tissue damage after OLT and liver resection induces increased serum levels of multiple cytokines but only ischemia/reperfusion injury associated with OLT results in the remarkable mobilization of BM stem/progenitor cells.
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PMID:Mobilization of bone marrow-derived hematopoietic and endothelial stem cells after orthotopic liver transplantation and liver resection. 1693 69

This study aimed to develop and validate a comprehensive model that predicts survival after liver transplantation based on pretransplant donor and recipient characteristics. Complete data were available from the United Network for Organ Sharing for 20,301 persons who underwent liver transplantation in the United States between 1994 and 2003. Proportional-hazards regression was used to identify the donor and recipient characteristics that best predicted survival and incorporate these characteristics in a multivariate model. A data-splitting approach was used to compare survival predicted by the model to the observed survival in samples not used in the derivation of the model. A model was derived using 4 donor characteristics (age, cold ischemia time, gender, and race/ethnicity) and 9 recipient characteristics (age, body max index, model for end-stage liver disease score, United Network for Organ Sharing priority status, gender, race/ethnicity, diabetes mellitus, cause of liver disease, and serum albumin) that adequately predicted survival after liver transplantation in patients without hepatitis C virus, and a slightly different model was used for patients with hepatitis C virus. The models illustrate that variations in both pretransplant donor and recipient characteristics have a large effect on posttransplant survival. In conclusion, the models presented here can be used to derive scores that are proportional to the excess risk of graft loss after liver transplantation for potential donors, recipients, or donor/recipient combinations. The models may be used to inform liver transplant candidates and their doctors what posttransplant survival would be expected when a given donor is offered and may be particularly helpful for marginal or high-risk donors.
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PMID:Development and validation of a model predicting graft survival after liver transplantation. 1753 90

A 64-year-old man with portal hypertension secondary to hepatic nodular transformation was awaiting liver transplantation when he presented with severe, unrelenting abdominal pain, fever, and hypotension. Computed tomographyrevealed pneumatosis within the cecum and ascending colon. Because of his advanced liver disease and the perceived high likelihood of a poor outcome after colonic resection, he was managed medically. He improved initially but had a lengthy hospital course notable for intractable intestinal ischemia and gastrointestinal bleeding. Magnetic resonance angiography demonstrated patent mesenteric, portal, and hepatic vessels. His blood pressure was typically 90/55 mm Hg (mean arterial pressure, 65-70 mm Hg) despite intravenous fluids and blood product replacement. The hypothesis developed that the patient's level of portal hypertension was sufficiently severe (in the face of his low mean systemic arterial pressure) to compromise perfusion of the colonic mucosa. Were this hypothesis correct, then portal decompression might enhance the blood pressure gradient across the bowel and improve mucosal perfusion. With this in mind, a transjugular intrahepatic portosystemic shunt (TIPS) was placed. There was reduction of the portal vein to inferior vena cava gradient from 29 mm Hg to 9 mm Hg and his abdominal pain and gastrointestinal bleeding ceased. His prompt and sustained improvement following TIPS shunt placement is consistent with the hypothesis that high portal pressure was flow limiting, thus contributing to persisting intestinal ischemia. This case represents the first report of use of a TIPS shunt to address colonic ischemia associated with portal hypertension.
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PMID:Transjugular intrahepatic portosystemic shunt for treatment of intractable colonic ischemia associated with portal hypertension: a bridge to liver transplantation. 1700 62

The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors. Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases.
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PMID:The complement system in liver diseases. 1709 30


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