Luiz Eduardo Correia Miranda

As bases experimentais da lesão por isquemia e reperfusão do fígado: revisão

Hepatic transplantation has become the main treatment for patients with terminal hepatic disease. Whatever the success of such surgery, the hepatic dysfunction associated with liver transplantation is an important cause of morbidity and mortality. Paradoxically, on restoring the blood supply, the liver is subjected to a further insult, aggravating the injury already caused by ischemia. This complex phenomenon is termed ischemia-reperfusion injury and involves endothelial cell dysfunction, leukocyte entrapment, platelet aggregation, oxidant stress and hepatic microcirculatory perfusion failure. This review discusses the physiopathlogicals mechanisms of liver ischemia-reperfusion injury.

Endothelium-dependent and -independent hepatic artery vasodilatation is not impaired in a canine model of liver ischemia-reperfusion injury.

We investigated whether hepatic artery endothelium may be the earliest site of injury consequent to liver ischemia and reperfusion. Twenty-four heartworm-free mongrel dogs of either sex exposed to liver ischemia/reperfusion in vivo were randomized into four experimental groups (N = 6): a) control, sham-operated dogs, b) dogs subjected to 60 min of ischemia, c) dogs subjected to 30 min of ischemia and 60 min of reperfusion, and d) animals subjected to 45 min of ischemia and 120 min of reperfusion. The nitric oxide endothelium-dependent relaxation of hepatic artery rings contracted with prostaglandin F2a and exposed to increasing concentrations of acetylcholine, calcium ionophore A23187, sodium fluoride, phospholipase-C, poly-L-arginine, isoproterenol, and sodium nitroprusside was evaluated in organ-chamber experiments. Lipid peroxidation was estimated by malondialdehyde activity in liver tissue samples and by blood lactic dehydrogenase (LDH), serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) activities. No changes were observed in hepatic artery relaxation for any agonist tested. The group subjected to 45 min of ischemia and 120 min of reperfusion presented marked increases of serum aminotransferases (ALT = 2989 +/- 1056 U/L and AST = 1268 +/- 371 U/L; P < 0.01), LDH = 2887 +/- 1213 IU/L; P < 0.01) and malondialdehyde in liver samples (0.360 +/- 0.020 nmol/mgPT; P < 0.05). Under the experimental conditions utilized, no abnormal changes in hepatic arterial vasoreactivity were observed: endothelium-dependent and independent hepatic artery vasodilation were not impaired in this canine model of ischemia/reperfusion injury. In contrast to other vital organs and in the ischemia/reperfusion injury environment, dysfunction of the main artery endothelium is not the first site of reperfusion injury.

Emprego do escore MELD para a predição da sobrevivência pós-transplante hepático

OBJECTIVE To assess the overall accuracy of the preoperative MELD score for predicting survival after liver transplantation (LT) and appraise medium-term (24 months) predictors of survival. METHODS We conducted a cross-sectional study including patients transplanted by the Department of General Surgery and Liver Transplantation of the Oswaldo Cruz University Hospital, University of Pernambuco, between July 15th, 2003 and July 14th, 2009. We used analysis of area under ROC (receiver operating characteristic) as a summary measure of the performance of the MELD score and assessed predictors of medium-term survival using univariate and multivariate analysis. RESULTS The cumulative survival of three, six, 12 and 24 months of the 208 patients studied was 85.1%, 79.3%, 74.5% and 71.1%, respectively. The preoperative MELD score showed a low discriminatory power for predicting survival after TH. By univariate analysis, we identified intraoperative transfusion of red blood cells (p <0.001) and platelets (p = 0.004) and type of venous hepatocaval anastomosis (p = 0.008) as significantly related to medium-term survival of the patients studied. However, by multivariate analysis only red blood cell transfusion was a significant independent predictor of outcome. CONCLUSION The MELD score showed low overall accuracy for predicting post-transplant survival of patients studied, among which only intraoperative transfusion of red blood cells was identified as an independent predictor of survival in the medium term after TH.

A ATIVIDADE RESPIRATÓRIA MITOCONDRIAL É UM BOM PARÂMETRO PARA A LESÃO POR ISQUEMIA E REPERFUSÃO HEPÁTICA

BACKGROUND Mitochondrial respiratory activity is associated with hepatic ischemia/reperfusion injury. AIM To determine in vitro whether hepatic ischemia/reperfusion injury may be detected regardless mitochondrial respiratory activity. MATERIAL AND METHODS Twenty-four heartworm-free mongrel dogs of either sex were randomized in the following groups: control, sham-operated dogs; I60, dogs subjected to 60 min of liver ischemia; I30/R60, dogs subjected to 30 min of ischemia e 60 min of reperfusion of liver; I45/R120 animals subjected to 45 min of ischemia and 120 min of reperfusion of liver. Blood and liver samples were taken after surgery to be processed. Mitochondrial respiratory activity was measured with a Clark-type oxygen electrode and mitochondrial membrane potential was calculated. lactic dehydrogenase, aspartate amino transferase and alanine aminotrasferase activities were determinated using laboratory kits, and malondialdehyde content in liver samples was estimated. RESULTS The group I45/R120 showed increases of serum aminotransferase, lactic dehydrogenase and malondialdehyde in liver samples. Whereas no changes were registered in mitochondrial respiratory activities and mitochondrial membrane potential, a tendency of decrease in the rate of active respiration (state 3) could be observed. CONCLUSION Under the conditions of this study, the results suggest the data from mitochondrial respiratory activity could show no significance difference among groups in hepatic ischemia/reperfusion injury. Hepatic ischemia reperfusion injury can be detected regardless mitochondrial respiratory activity.

Postoperative kidney injury does not decrease survival after liver transplantation

PURPOSE To explore the effect of acute kidney injury (AKI) on long-term survival after conventional orthotopic liver transplantation (OLT) without venovenous bypass (VVB). METHODS A retrospective cohort study was carried out on 153 patients with end-stage liver diseases transplanted by the Department of General Surgery and Liver Transplantation of the University of Pernambuco, from August, 1999 to December, 2009. The Kaplan-Meier survival estimates and log-rank test were applied to explore the association between AKI and long-term patient survival, and multivariate analyses were applied to control the effect of other variables. RESULTS Over the 12.8-year follow-up, 58.8% patients were alive with a median follow-up of 4.5-year. Patient 1-, 2-, 3- and 5-year survival were 74.5%, 70.6%, 67.9% and 60.1%; respectively. Early postoperative mortality was poorer amongst patients who developed AKI (5.4% vs. 20%, p=0.010), but long-term 5-year survival did not significantly differed between groups (51.4% vs. 65.3%; p=0.077). After multivariate analyses, AKI was not significantly related to long-term survival and only the intraoperative transfusion of red blood cells was significantly related to this outcome (non-adjusted Exp[b]=1.072; p=0.045). CONCLUSION The occurrence of postoperative acute kidney injury did not independently decrease patient survival after orthotopic liver transplantation without venovenous bypass in this data from northeast Brazil.

O doador marginal: experiência de um centro de transplante de fígado

RACIONAL: Desde que o uso de enxertos marginais e solucao aceita para escassez de orgaos para transplante, ele tornou-se muito comum em todo mundo e a literatura vem mostrando efetividade desses enxertos no transplante de figado. OBJETIVO: Apresentar a experiencia do Servico de Transplante Hepatico do Hospital Universitario Oswaldo Cruz, em transplante de figado com o uso de doadores marginais. METODOS: Estudo retrospectivo em 137 transplantes ortotopicos de figado, usando enxertos marginais entre 1999 e 2006, com acompanhamento minimo de 180 dias. Os receptores foram classificados de acordo com a funcao inicial do enxerto no pos-operatorio como normal (FN) e disfuncao primaria (DP). RESULTADOS: Nao foi observada diferenca estatisticamente significante entre os grupos FN e DP com os seguintes parâmetros dos doadores: idade, sodio serico, tempo de protrombina, esteatose hepatica, transaminases serica, pressao sanguinea, drogas vasoativas, indice de massa corporea, parada cardiaca antes da doacao de orgao, doador em assistolia e tempo de isquemia quente. Analise da curva de sobrevida (Kaplan-Meier) de pacientes e de enxertos de figado de pacientes que receberam figado de doadores ideais versus doadores marginais nao mostrou diferenca com significância estatistica. CONCLUSAO: Pode ser recomendado o uso de enxertos marginais para transplantes hepaticos, inclusive os provenientes de doadores com o coracao parado.

Non-cancerous prognostic factors of hepatocellular carcinoma after liver transplantation

PURPOSE To explore non-cancerous factors that may be related with medium-term survival (24 months) after liver transplantation (LT) in this data from northeast Brazil. METHODS A cross-sectional study was carried out in patients who underwent deceased-donor orthotopic LT because hepatocellular carcinoma (HCC) at the University of Pernambuco, Brazil. Non-cancerous factors (i.e.: donor-, receptor-, surgery- and center-related variables) were explored as prognostic factors of medium-term survival using univariate and multivariate approachs. RESULTS Sixty-one patients were included for analysis. Their three, six, 12 and 24-month overall cumulative survivals were 88.5%, 80.3%, 73.8% and 65.6%, respectively. Our univariate analysis identified red blood cell transfusion (Exp[b]=1.26; p<0.01) and hepato-venous reconstruction technique (84.6% vs. 51.4%, p<0.01; respectively for piggyback and conventional approaches) as significantly related to post-LT survival. The multivariate analysis confirmed the hepato-venous reconstruction technique was an independent prognostic factor. CONCLUSION The piggyback technique was related to improved medium-term survival of hepatocellular carcinoma patients after liver transplantation in this northeast Brazilian sample.

Effects on growth after hypertension portal induced in young rats

BACKGROUND: Physical growth retardation in children with hypertension portal was observed regardless of schistosomiasis. It has been suggested that the shunt of portal blood through portosystemic collateral vessels would result in metabolic consequences that would lead to the physical growth deficit observed. AIM: Study the effects of hypertension portal in the growth of young rats. METHODS: The growth of 20 young rats, divided in the groups hypertension portal, n = 10, 103 3.7 g and sham operation n = 10, 102.6 ± 3.4 g was evaluated throughout 5 weeks and the following parameters were under observation: quality of diet offered, diet ingestion, weight increase and urinary creatinine within 24 hours. At the end of the experiment, blood was taken for biochemical tests, prothrombin time and hematocrit and hypertension portal was measured. RESULTS/CONCLUSIONS: Rats with hypertension portal induced at early stages of their lives present growth delay in the first week after surgery recovering their growth rhythm in the next weeks, catching up with the sham animals. Differences related to urinary creatinine excretion, biochemical tests and hematocrit were not observed. Such results are evidence against the hypothesis that the hypertension portal induced in early stages of rats lives would cause delay in their growth.