Luiz Pereira-Lima

The role of nitric oxide pathway in the renal ischemia-reperfusion injury in rats.

INTRODUCTION Nitric oxide (NO), synthesized from L-arginine by the enzyme nitric oxide synthase (NOS), seems to play an ambiguous role during tissue ischemia-reperfusion injury. Our objective was to evaluate the effects of L-arginine, a NO donor, and N(G)-nitro-L-arginine-methylester (L-NAME), a NOS inhibitor, on oxidative stress, renal dysfunction, histologic alterations and surgical mortality rate induced by renal ischemia-reperfusion (RIR) in uninephrectomized rats. MATERIALS AND METHODS One-hundred and ninety-seven Wistar rats were randomized into five experimental groups. Group 1: sham operation; group 2: right uninephrectomy (UNI); group 3: UNI + RIR in the contralateral kidney; group 4: UNI + L-NAME (20 mg/kg; intraperitoneally) + RIR; and group 5: UNI + L-arginine + RIR. The effect of the drugs was evaluated by lipid peroxidation measured by the renal malondialdehyde (MD) content and chemiluminescence (CL) levels, serum creatinine (Cr) levels, urinary volume, tubular necrosis and athrophy, inflammatory infiltrate, interstitial fibrosis as histologic evaluation and surgical mortality rate after the procedures. A P value less than 0.05 was considered significant. RESULTS Right uninephrectomy did not alter the renal parameters. RIR increased Cr levels (at 24 and 96 h of reperfusion), index of lipid peroxidation (both MD and QL levels), and worsened the histologic aspects. Pretreatment with L-arginine reduced the kidney levels of QL when compared with the non-treated group (5574 +/- 909 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) but increased the MD levels (0.97 +/- 0.24 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Moreover, L-arginine attenuated the increment of Cr levels, inflammatory infiltrate and tubular athrophy in rats subjected to RIR (P < 0.05). On the other hand, pretreatment with L-NAME increased both CL (17 482 +/- 4397 vs. 13 660 +/- 1104 cps/mg of protein; P < 0.05) and MD levels (1.16 +/- 0.11 vs. 0.79 +/- 0.06 nmol/mg of protein; P < 0.05). Furthermore, L-NAME worsened the renal dysfunction (P < 0.05) at 192 h after the RIR, and surgical mortality rates were similar (P > 0.05). CONCLUSION L-arginine has a tendency to exert a beneficial effect on renal damage during RIR in rats. Moreover, L-NAME seems to worsen the renal damage by increasing the kidney-levels of CL and impairment of renal function probably due to reduction of NO production.

Risk factors for postoperative acute renal failure at a new orthotopic liver transplantation program.

ACUTE RENAL failure (ARF) is a frequently observed complication during the postoperative period of orthotopic liver transplantation (OLT) when the rate of reported renal failure varies according to the postoperative period and serum creatinine levels considered. Although some patients require dialysis, most recover normal renal function. ARF is one of the most frequent causes of morbidity and mortality after OLT, and Nuno et al indicate a 7.8 higher probability of mortality in patients who have undergone ARF, and 15 times higher than that for those patients who required dialysis. Various factors are outstanding in the preoperative and postoperative periods, as well as during surgery, which could explain the occurrence of ARF. Preoperative factors include: diabetes mellitus, a history of ascites and encephalopathy, and previous kidney lesion. Crawford et al described the occurrence of glomerular lesions as universal to all patients with end-stage liver disease. During surgery, hypovolemia, the number of packed red blood cell (PRBC) units required and the time of total ischemia are described as associated factors. Several series correlate the use of nephrotoxic drugs, such as cyclosporine A (CyA), as a factor which could contribute to renal lesions. However, this may also be the result of complications such as sepsis and multiorgan failure. The purpose of this study is to assess the factors associated with the development of renal failure during the immediate postoperative period of an initial OLT program.

The Effects of Allopurinol in Hepatic Ischemia and Reperfusion: Experimental Study in Rats

Background/Aims: Some studies have shown that postischemic hepatic dysfunction is mainly due to oxygen free radicals that are generated by xanthine oxidase. The present study was undertaken to determine the effect of allopurinol, an inhibitor of xanthine oxidase, on oxidative stress, liver injury and histologic alterations induced by hepatic ischemia-reperfusion in rats. Methods: One hundred and sixty Wistar rats were used and divided into three groups. Group 1: sham operation; group 2: 50 min of ischemia followed by 1 h of reperfusion, and group 3: pretreatment with allopurinol and 50 min of ischemia followed by 1 h of reperfusion. The effect of allopurinol was evaluated by plasma levels of alanine aminotransferase and aspartate aminotransferase, histopathologic studies, and lipid peroxidation measured by the thiobarbituric acid reactive substances method and chemiluminescence initiated by tert-butyl hydroperoxide technique. Results: Ischemia followed by reperfusion promoted an increase in lipid peroxidation of the hepatic cells when compared to the sham-operated group (p < 0.05). This increase was attenuated in the group treated with allopurinol (p < 0.05). Allopurinol also showed a protective effect on hepatocellular necrosis (p < 0.05), and the plasma levels of liver enzymes returned earlier to the normal range in rats pretreated with allopurinol in comparison to those that did not receive the drug (p < 0.05). Conclusions: Allopurinol exerted a protective effect on hepatic ischemia and reperfusion in rats. The administration of this drug prior to liver operations should be considered to be submitted to trials in humans.

Role of the L-Arginine/Nitric Oxide Pathway in Renal Ischaemia-reperfusion in Rats

OBJECTIVE To study the role of the L-arginine/nitric oxide (NO) pathway during renal ischaemia-reperfusion in rats. DESIGN Randomised experimental study. SETTING Teaching hospital, Brazil. ANIMALS 97 male Wistar rats randomly assigned to 4 groups for the assessment of renal dysfunction and to 6 groups for the assessment of the oxidative stress induced on renal cell membranes by ischaemia-reperfusion. INTERVENTIONS The animals underwent sham-operation or renal ischaemia-reperfusion (n = 9 each) with or without pretreatment with L-arginine (a NO donor) or L-NAME (N(omega)-nitro-L-arginine methyl ester--an inhibitor of NO production) (n = 10 each). MAIN OUTCOME MEASURES Serum creatinine concentrations and oxidative stress by chemiluminescence initiated by the tert-butyl hydroperoxide technique. RESULTS Renal ischaemia-reperfusion significantly worsened renal dysfunction and increased oxidative stress in the ischaemia-reperfusion group after 24 and 96 hours of reperfusion compared with the control group (p < 0.05). Pretreatment with L-NAME slightly but not significantly increased serum creatinine concentrations after 24 and 96 hours of reperfusion together with activity of reactive oxygen species during renal ischaemia-reperfusion. L-arginine also significantly protected renal function and reduced the increment in the amount of chemiluminescence induced by giving L-NAME during 24 and 96 hours of reperfusion (p < 0.05). CONCLUSION The L-arginine/NO pathway seems to have a slightly protective effect on the kidney after renal ischaemia-reperfusion injury in rats. These results need to be confirmed by studies in human beings.

Liver resections for metastases from intraabdominal Leiomyosarcoma

This paper discusses liver resection for intraabdominal leiomyosarcoma metastases as a therapy for carefully selected patients. Of the 83 hepatectomies performed from 1992 to 1996, five were resections for liver metastases due to intraabdominal leiomyosarcoma, in 3 patients. The surgical indication was single liver metastases, without any evidence of extrahepatic disease. No mortality occurred during surgery and the longest survival was 38 months. We concluded that liver resection for leiomyosarcoma metastases can be performed, allowing a long term survival in an occasional patient.

Utilização das hepatectomias centrais nas cirurgias hepatobiliares

The treatment of hepatobiliary diseases by central hepatectomies has been one of the most important challenges in surgical technique at the end of this century. Although different techniques were used in the last decades, only recently they have been carried out safely, drastically reducing the morbidity and mortality rates, and thus providing favorable results in treating different hepatic diseases. Whether the liver does or not present chronic liver disease, the integration of related multiple-disciplinary teams in this type of surgery and disease has allowed complex ablations, sometimes bordering on the limit of the possibility of life.Based on the principle of maintaining a viable remaining hepatocyte mass and function, the morphological and functional study of the liver during the preoperative period requires the frequent use of techniques to transplant liver segments, both for vascular reconstruction and for the reduction and conservation of the liver mass. Thus, the resection of any part of the liver with a minimum use of blood products has proved feasible with thorough knowledge of the anatomy of the liver, and the use of echography during surgery. Different central hepatectomy techniques are, thus, presented, discussing indications and surgical details of each of them.

Taxa de mortalidade em ratos submetidos à isquemia e reperfusão hepática, tratados ou não com alopurinol

A isquemia transitoria hepatica tem sido cada vez mais amplamente utilizada. Contudo, essa atitude, embora muitas vezes benefica, e contrabalancada pelos efeitos adversos advindos da isquemia hepatica e da congestao esplenica, assim como, das consequencias da reperfusao. O objetivo dos autores e determinar os efeitos da isquemia seletiva em animais pre-tratados ou nao com alopurinol, inibidor da xantina oxidase sobre a mortalidade dos animais. Foram utilizados 30 ratos assim divididos: Grupo I (n=10): pre-tratados com alopurinol e submetidos a laparotomia e exposicao do pediculo hepatico por 45 minutos. Grupo II (n=10): tratados com alopurinol e submetidos a isquemia hepatica seletiva por 45 minutos. Grupo III (n=10): submetidos apenas a isquemia por 45 minutos. A mortalidade pos-operatoria foi avaliada a cada 24 horas, por um periodo de 10 dias. Entre os animais do grupo I, nao foram observados obitos, entretanto, naqueles dos grupos II e III, as mortalidades globais foram respectivamente 20 e 46,7%. Diferenca estatisticamente significativa, apenas, entre a mortalidade observada no grupo III em relacao ao controle (p<0,05). A mortalidade pos-operatoria no grupo de animais submetidos a isquemia sem pre-tratamento com alopurinol ascende as cifras de 46,67% dos animais, enquanto naqueles pre-tratados com alopurinol houve um importante decrescimo para 20%. Embora sem uma distincao estatisticamente significativa, reflete uma tendencia de um efeito protetor do alopurinol na isquemia e reperfusao hepatica.

Fístula cervical pós-anastomose esofagogástrica: é possível diminuir a ocorrência?

INTRODUCAOA esofagectomia e procedimento cirurgico complexo e tradicionalmente associado a morbidade significativa, tendo como principal indicacao o tratamento da doenca maligna. Neste caso, apesar dos progressos em outras modalidades terapeuticas, a esofagectomia persiste como tratamento de escolha em pacientes com tumores poten-cialmente ressecaveis, tanto com intento curativo quanto paliativo. Entretanto, na afeccao maligna, cerca de 75% dos pacientes ja apresentam doenca avancada no momento do diagnostico

Ressecções hepáticas com oclusão vascular aferente: análise de fatores de risco

BACKGROUND: The control of blood loss during liver resection has been related to lower rates of perioperative mortality and morbidity. Techniques to minimize intraoperative bleeding are associated with blood flow interruption to the liver, either through an afferent vascular occlusion (Pringle maneuver) or by total vascular isolation of the organ. The aim of this study was to evaluate a series of partial hepatectomies with afferent blood flow occlusion, in patients with benign or malignant diseases. METHOD: Sixty hepatic resections with inflow occlusion, in 59 patients, were analyzed in order to search possible risk factors for morbidity and mortality, the connection between the hepatic ischemic time and the transaminases variation, the prothrombin time and bilirrubins and the postoperative evolution. RESULTS: The prevalence of postoperative complications was 43% and the mortality rate was 6.7%. The significant risk factor for mortality was the long lasting operative time when compared to patients who did not die. For the postoperative morbidity, the identified risk factors were age over sixty years old, surgery for malign neoplasm, abnormal liver parenchyma, blood loss demanding replacement of more than one unity of blood transfusion and another concomitant abdominal surgery. In a multiple regression analysis, those risk factors were reduced only to abnormal hepatic parenchyma. CONCLUSIONS: The ischemia time did not have any connection with the postoperative morbidity or mortality. The transaminases levels were higher in cases of longer ischemic time, however they returned to the preoperative levels in about a week. The transaminases variations were not different amongst patients who had postoperative morbidity or not.