ABSTRACT Purpose: To evaluate local and systemic effects of 24-hour fasting in liver ischemia and reperfusion injury. Methods: Twenty-one adult male Wistar rats (330–390 g) were submitted to 60 minutes of hepatic ischemia followed by 24 hours of reperfusion. Before the day of the experiment, the animals fasted, but free access to water was allowed. Two groups were constituted: Control: non-fasted, that is, feeding ad libitum before surgical procedure; Fasting: rats underwent previous fasting of 24 hours. Hepatic ischemia was performed using vascular clamp in hepatic pedicle. At 24 hours after liver reperfusion, blood and tissue samples were collected. To analysis, liver lobes submitted to ischemia was identified as ischemic liver and paracaval non-ischemic lobes as non-ischemic liver. We evaluated: malondialdehyde levels, hepatocellular function (alanine aminotransferase, aspartate aminotransferase activities, and both ratio), cytokines (interleukins-6, -10, and tumor necrosis factor-alpha), hepatic ischemia and reperfusion injury (histology). Results: Malondialdehyde measured in non-ischemic and ischemic liver samples, hepatocellular function and cytokines were comparable between groups. Histological findings were distinct in three regions evaluated. Microvesicular steatosis was comparable between 24-hour fasting and non-fasted control groups in periportal region of hepatic lobe. In contrast, steatosis was more pronounced in zones 2 and 3 of ischemic liver samples of fasting compared to control groups. Conclusions: These data indicates that fasting does not protect, but it can be also detrimental to liver submitted to ischemia/reperfusion damage. At that time, using long fasting before liver surgery in the real world may be contraindicated.

OBJECTIVES: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage. METHODS: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection. RESULTS: We show that liver resection is associated with significant intestinal barrier injury, even if the Pringle maneuver is not performed. CONCLUSION: We propose the use of insulin-like growth factor binding protein-1 as a novel biomarker of intestinal damage in such situations.

PURPOSE: To evaluate the underlying mechanisms by which sevoflurane protects the liver against ischemia/reperfusion injury evaluate the mechanism by which sevoflurane exerts this protective effect. METHODS: Twenty-six rats were subjected to partial ischemia/reperfusion injury for 1h: one group received no treatment, one group received sevoflurane, and sham group of animals received laparotomy only. Four hours after reperfusion, levels of alanine and aspartate aminotransferases, tumor necrosis factor-a, and interleukins 6 and 10 were measured. Analyses of mitochondrial oxidation and phosphorylation, malondialdehyde content, histology, and pulmonary vascular permeability were performed. RESULTS: Serum levels of alanine and aspartate aminotransferases were significantly lower in the sevoflurane group compared to untreated controls (p<0.05). The sevoflurane group also showed preservation of liver mitochondrial function compared to untreated controls (p<0.05). Sevoflurane administration did not alter increases in serum levels of tumor necrosis factor-a, and interleukins 6 and 10. Sevoflurane treatment significantly reduced the coagulative necrosis induced by ischemia/reperfusion (p<0.05). Pulmonary vascular permeability was preserved in the sevoflurane group compared to untreated controls. CONCLUSION: Sevoflurane administration protects the liver against ischemia/reperfusion injury, via preservation of mitochondrial function, and also preserves lung vascular permeability.

Objetivo: Avaliar e compreender as implicações clínicas dos níveis plasmáticos de uma isoforma solúvel de um receptor de produtos finais de glicação avançada (do inglês receptor for advanced glycation end products - sRAGE) em diferentes fases da sepse. Métodos: Os valores do sRAGE sérico em pacientes divididos nos grupos controle na unidade de terapia intensiva, sepse grave, choque séptico e recuperação de choque séptico foram analisados do ponto de vista estatístico para avaliar a quantidade (Kruskal-Wallis), variabilidade (teste de Levine) e correlação (teste Spearman rank) em relação a certos mediadores inflamatórios (IL-1 α, IL-6, IL-8, IL-10, IP-10, G-CSF, MCP-1, IFN-γ e TNF-α). Resultados: Não se observaram modificações nos níveis de sRAGE entre os grupos; contudo o grupo com choque séptico demonstrou diferenças na variabilidade do sRAGE em comparação aos demais grupos. Foi relatada, no grupo com choque séptico, uma correlação positiva com todos os mediadores inflamatórios. Conclusão: Os níveis de sRAGE se associaram com desfechos piores nos pacientes com choque séptico. Entretanto, uma análise de correlação estatística com outras citocinas pró-inflamatórias indicou que as vias que levam a esses desfechos são diferentes, dependendo dos níveis de sRAGE. A realização de estudos futuros para elucidar os mecanismos fisiopatológicos que envolvem sRAGE nos modelos de sepse será de grande importância clínica para possibilitar o uso seguro desse biomarcador.

OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

OBJETIVO: Investigar os efeitos da pentoxifilina (PTX) na pancreatite aguda (PA) experimental administrando a droga após a indução da doença. MÉTODOS: Cem ratos machos Wistar foram submetidos à indução da PA através da infusão de taurocolato de sódio e divididos em três grupos: Grupo Sham: sham-operated ratos, Grupo Salina: AP e solução salina, e Grupo PTX: AP e PTX. Solução salina e PTX foram administradas 1 hora após a indução da PA. Três horas após indução da PA os níveis de fator de necrose tumoral (TNF)-α no líquido peritoneal e os níveis séricos de interleucina (IL)-6 e IL-10 foram analisados pelo método de Enzima Imunoensaio (ELISA). A atividade da mieloperoxidase (MPO) foi analisada no pulmão e foram realizadas análises histológicas do pulmão e pâncreas, além do estudo da mortalidade. RESULTADOS: A administração de PTX 1 hora após a indução da PA reduziu significativamente os níveis de TNF-α peritoneal e os níveis séricos de IL-6 e IL-10 quando comparado ao grupo salina. Redução na mortalidade foi observado após o tratamento com PTX comparado ao grupo salina. CONCLUSÃO: A administração de PTX após a indução da PA diminuiu os níveis sistêmicos de citocinas pró-inflamatórias, sugerindo a possibilidade de que existe uma janela terapêutica para PTX após o início do PA.

PURPOSE: To investigate the effects of pentoxifylline (PTX) in experimental acute pancreatitis (AP) starting drug administration after the induction of the disease. METHODS: One hundred male Wistar rats were submitted to taurocholate-induced AP and divided into three groups: Group Sham: sham-operated rats, Group Saline: AP plus saline solution, and Group PTX: AP plus PTX. Saline solution and PTX were administered 1 hour after induction of AP. At 3 hours after AP induction, peritoneal levels of tumor necrosis factor (TNF)-α, and serum levels of interleukin (IL)-6 and IL-10 levels were assayed by Enzyme-Linked Immunosorbent Assay (ELISA). Determinations of lung myeloperoxidase activity (MPO), histological analysis of lung and pancreas, and mortality study were performed. RESULTS: PTX administration 1 hour after induction of AP caused a significant decrease in peritoneal levels of TNF-α and in serum levels of IL-6 and IL-10 when compared to the saline group. There were no differences in lung MPO activity between the two groups with AP. A decrease in mortality was observed in the PTX treatment compared to the saline group. CONCLUSIONS: Administration of PTX after the onset of AP decreased the systemic levels of proinflammatory cytokines, raising the possibility that there is an early therapeutic window for PTX after the initiation of AP.

OBJETIVO: Descrever um modelo experimental de lesão de isquemia/reperfusão hepática com manifestações sistêmicas, representadas pelo envolvimento pulmonar, que possa ser utilizado por aqueles que pretendem compreender esse fenômeno. MÉTODOS: Ratos Wistar machos (200-250g) foram usados. Quatorze foram alocados em dois grupos, sendo G1 com oito submetidos somente à laparotomia e G2, seis à isquemia e reperfusão hepática. As funções hepática (aminotransferases séricas, respiração mitocondrial, histologia) e pulmonar (teste do azul de Evans) foram analisadas. RESULTADOS: houve diferença estatística significativa entre G1 e G2 ao se comparar valores de AST (24,3 ± 108 e 5406 ± 2263), ALT (88,5 ± 28,5 e 5169 ± 2690), razão de controle respiratório (3,41 ± 0,17 e 1,91 ± 0,55) e relação ADP/O (1,93 ± 0,03 e 1,45 ± 0,27), lesões histológicas (necrose, células inflamatórias, hemorragia, microesteatose) e teste do azul de Evans (194,31 ± 53 e 491,8 ± 141). CONCLUSÃO: O modelo mostrou-se útil para o estudo de lesão de isquemia/reperfusão hepática.

OBJECTIVE: To describe an experimental model of hepatic ischemia/reperfusion injury with systemic manifestations, represented by pulmonary involvement, which may be used by those who intend to comprehend this phenomenon. METHODS: Fourteen Male Wistar rats (200-250g) were allocated to two groups, G1 with eight rats submitted only to laparotomy and G2, six rats submitted to hepatic ischemia and reperfusion. Hepatic (serum aminotransferases, mitochondrial respiration, histology) and pulmonary (Evans blue test) functions were analyzed. RESULTS: There was a statistically significant difference (p< 0.05) between G1 and G2 comparing values of AST (24,3 ± 108 and 5406 ± 2263), ALT (88,5 ± 28,5 and 5169 ± 2690), respiratory control ratio (3,41 ± 0,17 and 1,91 ± 0,55) and ADP/O relation (1,93 ± 0,03 and 1,45 ± 0,27), histological lesions (necrosis, inflammatory cells, hemorrhage, microsteatosis) and Evans blue test (194,31 ± 53 and 491,8 ± 141). CONCLUSION: The model has proven useful to study hepatic I/R injury.

Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and localization of multiple endocrine neoplasia type 1related tumors are crucial for determining the best surgical strategies in each individual case with pancreatic endocrine tumors.

JUSTIFICATIVA E OBJETIVOS: Uma compreensão melhor das alterações fisiopatológicas associadas ao trauma e ao choque hemorrágico pode ajudar no desenvolvimento de terapêuticas capazes de reduzir a mortalidade relacionada ao trauma. O objetivo deste estudo é descrever um modelo de choque hemorrágico não controlado em porcos. MÉTODOS: Como medicação pré-anestésica, os animais receberam cetamina e midazolan. A anestesia foi induzida com propofol e a intubação traqueal foi realizada na vigência de respiração espontânea. Após a intubação, realizou-se bloqueio neuromuscular. Os animais foram mantidos em respiração mecânica controlada e normocapnia. A anestesia foi mantida com propofol e fentanil, de acordo com a necessidade. Solução de soro fisiológico 0,9% foi infundida em todo o período de preparação. MONITORAÇÃO: Foram utilizados cardioscópio, oxímetro de pulso, medida de pressão arterial invasiva, cateter volumétrico de artéria pulmonar e medida de débito urinário por cistostomia. Modelo experimental: após registro inicial de variáveis hemodinâmicas, metabólicas e de coagulação, realizaram-se incisão subcostal direita e biópsia hepática do lobo esquerdo. A infusão de anestésicos foi reduzida, enquanto a de solução de salina isotônica interrompida. Uma incisão de 12 cm de extensão por 2 cm de profundidade foi feita no lobo hepático direito, seguida de divulsão digital do ferimento. Durante a fase de hemorragia, uma sonda de aspiração foi posicionada junto ao ferimento e o volume de sangue aspirado foi registrado. Quando a pressão arterial média chegou a 40 mmHg e o sangramento foi superior a 700 mL, pôde ser iniciada a fase de intervenção de acordo com o tipo de estudo. CONCLUSÃO: É importante continuar o desenvolvimento de modelos experimentais com o objetivo final de reduzir a alta mortalidade e os custos associados ao trauma.

BACKGROUND AND OBJECTIVES: A better understanding of pathophysiologic changes associated to trauma and hemorrhagic shock can help the development of therapies capable of reducing trauma-related mortality. The objective of this study was to describe a model of non-controlled hemorrhagic shock in pigs. METHODS: Animals received ketamine and midazolam as pre-anesthetic medications. Anesthesia was induced with propofol, and tracheal intubation was performed with the animals on spontaneous ventilation. After intubation neuromuscular blockade was performed. Animals were maintained in controlled mechanical ventilation and normocapnia. Anesthesia was maintained with propofol and fentanyl as needed. Saline was infused during the entire preparation period. MONITORING: Cardioscope, pulse oximeter, invasive blood pressure, volumetric catheter in the pulmonary artery, and urine output by cystostomy were used. Experimental model: after the initial recording of hemodynamic, metabolic, and coagulation variables, right subcostal incision and left lobe liver biopsy were performed. Anesthetic infusion was reduced while the infusion of saline was interrupted. An incision 12 cm long 2 cm deep was performed in the right liver lobe followed by digital divulsion of the wound. During the hemorrhagic phase, an aspiration probe was placed close to the wound and the volume of aspirated blood was recorded. When mean arterial pressure reached 40 mmHg and bleeding was above 700 mL the intervention phase was initiated according to the type of study. CONCLUSION: The development of experimental models to reduce high mortality and costs related to trauma is important.

JUSTIFICATIVA Y OBJETIVOS: Una comprensión mejor de las alteraciones fisiopatológicas asociadas al trauma y al choque hemorrágico, puede ayudar en el desarrollo de las terapéuticas capaces de reducir la mortalidad relacionada con el trauma. El objetivo de este estudio es describir un modelo de choque hemorrágico no controlado en cerdos. MÉTODOS: Como medicación preanestésica, los animales recibieron cetamina y midazolan. La anestesia fue inducida con propofol, y la intubación traqueal fue realizada con la respiración espontánea. Después de la intubación, se realizó el bloqueo neuromuscular. Los animales se mantuvieron bajo respiración mecánica controlada y normocapnia. La anestesia se mantuvo con propofol y fentanil, a tono con la necesidad. Una solución de suero fisiológico al 0,9% fue infundida durante todo el período de la preparación. MONITOREO: Se usaron el cardioscopio, oxímetro de pulso, medida de presión arterial invasiva, catéter volumétrico de arteria pulmonar y medida de débito urinario por cistostomía. Modelo experimental: después del registro inicial de las variables hemodinámicas, metabólicas y de coagulación, se realizaron la incisión subcostal derecha y la biopsia hepática del lóbulo izquierdo. La infusión de anestésicos fue reducida, mientras que la solución de salina isotónica se interrumpió. Una incisión de 12 cm de extensión por 2 cm de profundidad se hizo en el lóbulo hepático derecho, seguida de una divulsión digital de la herida. Durante la fase de hemorragia, una sonda de aspiración fue posicionada junto a la herida, y el volumen de sangre aspirado fue registrado. Cuando la presión arterial promedio llegó a 40 mmHg y el sangramiento fue superior a 700 mL, pudo iniciarse la fase de intervención de acuerdo con el tipo de estudio. CONCLUSIÓN: Es importante continuar desarrollando modelos experimentales con el objetivo final de reducir la alta mortalidad y los costes asociados al trauma.

OBJETIVO: Desenvolver um modelo cirúrgico de IHA e hiperamonemia em ratos, que evita o shunt porto-sistêmico e a ligadura do ducto biliar, que seja aplicável à pesquisa de encefalopatia hepática. MÉTODOS: Após anestesia geral e laparotomia mediana, os pedículos dos lobos laterais direito e caudado foram isolados e clampeados. Após 1 hora, o animal foi reaberto, os clampes retirados e foi realizada hepatectomia anterior subtotal (ressecção dos lobos médio e lateral esquerdo), compreendendo a remoção de 75% do parênquima. Quatro horas após a hepatectomia, amostras de sangue e tecido hepático foram coletadas nos grupos IHA e controle. RESULTADOS: Diferenças entre os grupos IHA e controle foram significativas para ALT, AST, bilirrubina total e direta, sódio, potássio, fosfatase alcalina, gama glutamiltransferase e principalmente amônia. Histologicamente, diferenças significativas foram observadas entre os grupos. CONCLUSÃO: O modelo é útil para o estudo de aspectos específicos da IHA e o desenvolvimento de novas abordagens terapêuticas.

PURPOSE: To develop a reliable surgical model of acute hepatic failure and hyperammonemia in rats that avoids porto-systemic shunt and bile duct ligation, applicable to hepatic encephalopathy research. METHODS: The pedicles of right lateral and caudate lobes were exposed and clamped. One hour later, the animal was reopened, clamps were released and anterior subtotal hepatectomy (resection of median and left lateral lobes) was performed, comprising 75% of liver removal. Four hours after hepatectomy, blood samples and liver tissues were collected from ALF and control groups. RESULTS: Differences between ALF and control groups were significant for ALT, AST, total and direct bilirubin, sodium, potassium, alkaline phosphatasis, gamma-glutamyltransferase and most important, ammonia. Histologically, significant differences were noticed between groups. CONCLUSION: The model is useful for the study of specific aspects of ALF and the development of new therapeutic approaches.

BACKGROUND: Steatosis is currently the most common chronic liver disease and it can aggravate ischemia-reperfusion (IR) lesions. We hypothesized that S-nitroso-N-acetylcysteine (SNAC), an NO donor component, can ameliorate cell damage from IR injury. In this paper, we report the effect of SNAC on liver IR in rats with normal livers compared to those with steatotic livers. METHODS: Thirty-four rats were divided into five groups: I (n=8), IR in normal liver; II (n=8), IR in normal liver with SNAC; III (n=9), IR in steatotic liver; IV (n=9), IR in steatotic liver with SNAC; and V (n=10), SHAN. Liver steatosis was achieved by administration of a protein-free diet. A SNAC solution was infused intraperitoneally for one hour, beginning 30 min. after partial (70%) liver ischemia. The volume of solution infused was 1 ml/100 g body weight. The animals were sacrificed four hours after reperfusion, and the liver and lung were removed for analysis. We assessed hepatic histology, mitochondrial respiration, oxidative stress (MDA), and pulmonary myeloperoxidase. RESULTS: All groups showed significant alterations compared with the group that received SHAN. The results from the steatotic SNAC group revealed a significant improvement in liver mitochondrial respiration and oxidative stress compared to the steatotic group without SNAC. No difference in myeloperoxidase was observed. Histological analysis revealed no difference between the non-steatotic groups. However, the SNAC groups showed less intraparenchymal hemorrhage than groups without SNAC (p=0.02). CONCLUSION: This study suggests that SNAC effectively protects against IR injury in the steatotic liver but not in the normal liver.

OBJECTIVE: To evaluate the protective effects of N-acetyl cysteine on the pancreas and kidney after pancreatic ischemia reperfusion injury in a rat model. METHODS AND MATERIALS: Pancreatic ischemia reperfusion was performed in Wistar rats for 1 hour. Revascularization was achieved followed by 4 h of reperfusion. A total of 24 animals were divided into four groups: Group 1: sham; Group 2: pancreatic ischemia reperfusion without treatment; Group 3: pancreatic ischemia reperfusion plus N-acetyl cysteine intravenously; and Group 4: pancreatic ischemia reperfusion plus N-acetyl cysteine per os. Blood and tissue samples were collected after reperfusion. RESULTS: There were significant differences in amylase levels between Group 1 (6.11±0.55) and Group 2 (10.30±0.50) [p=0.0002] as well as between Group 2 (10.30±0.50) and Group 4 (7.82±0.38) [p=0.003]; creatinine levels between Group 1 (0.52 ± 0.07) and Group 2 (0.77±0.18) [p=0.035] as well as between Group 2 (0.77±0.18) and Group 3 (0.48±0.13) [p=0.012]; and pancreatic tissue thiobarbituric acid reactive substance levels between Group 1 (1.27±0.96) and Group 2 (2.60±3.01) [p=0.026] as well as between Group 2 (2.60±3.01) and Group 4 (0.52±0.56) [p=0.002]. A decrease in pancreatic tissue GST-α3 gene expression was observed in Group 2 in comparison to Group 1 (p =0.006), and an increase was observed in Groups 3 and 4 when compared to Group 2 (p= 0.025 and p=0.010, respectively). CONCLUSION: This study provides evidence that N-acetyl cysteine has a beneficial effect on pancreatic ischemia reperfusion injury and renal function in a rat model.

OBJECTIVE: This study was designed to evaluate the effects of terlipressin versus fluid resuscitation with normal saline, hypertonic saline or hypertonic-hyperoncotic hydroxyethyl starch, on hemodynamics, metabolics, blood loss and short-term survival in hemorrhagic shock. METHOD: Twenty-nine pigs were subjected to severe liver injury and treated 30 min later with either: (1) 2 mg terlipressin in a bolus, (2) placebo-treated controls, (3) 4 mL/kg 7.5% hypertonic NaCl, (4) 4 mL/kg 7.2% hypertonic-hyperoncotic hydroxyethyl starch 200/0.5, or (5) normal saline at three times lost blood volume. RESULTS: The overall mortality rate was 69%. Blood loss was significantly higher in the hypertonic-hyperoncotic hydroxyethyl starch and normal saline groups than in the terlipressin, hypertonic NaCl and placebo-treated controls groups (p<0.005). Hyperkalemia (K>5 mmol/L) before any treatment occurred in 66% of the patients (80% among non-survivors vs. 22% among survivors, p=0.019). Post-resuscitation hyperkalemia occurred in 86.66% of non-survivors vs. 0% of survivors (p<0.001). Hyperkalemia was the first sign of an unsuccessful outcome for the usual resuscitative procedure and was not related to arterial acidemia. Successfully resuscitated animals showed a significant decrease in serum potassium levels relative to the baseline value. CONCLUSION: Hyperkalemia accompanies hemorrhagic shock and, in addition to providing an early sign of the acute ischemic insult severity, may be responsible for cardiac arrest related to hemorrhagic shock.

OBJETIVO: A lesão de isquemia-reperfusão hepática é um fenômeno presente em eventos tais como ressecções hepáticas e transplante de fígado. A restauração do fluxo sangüíneo após a isquemia gera lesões locais e sistêmicas. Várias técnicas foram desenvolvidas com o objetivo de evitar ou diminuir a lesão de isquemia-reperfusão hepática em situações clínicas. A utilização da reperfusão intermitente após o evento isquêmico (pós-condicionamento) pode alterar a hidrodinâmica e estimular mecanismos endógenos que atenuam o dano da reperfusão. O presente estudo foi realizado para avaliar o potencial efeito protetor do pós-condicionamento em um modelo de isquemia-reperfusão em ratos. MÉTODOS: O pedículo dos lobos mediano e ântero-lateral foi isolado e clampeado por 1 hora. Após 2 horas, o pedículo foi liberado de duas maneiras diferentes: Grupo Controle (n=7): clampe liberado de uma só vez; Grupo Pós-condicionamento (n=7): clampe liberado de maneira intermitente. Malondialdeído (MDA) e expressão do gene GST- α3 foram estudadas nos grupos. RESULTADOS: A peroxidação lipídica foi significativamente diminuída no fígado isquêmico e no fígado não isquêmico pelo pós-condicionamento. A expressão do gene GST- α3 aumentou, porém não significativamente, no grupo pós-condicionamento. CONCLUSÃO: O pós-condicionamento induziu hepatoproteção pela redução da peroxidação lipídica nos fígados isquêmico e não isquêmico.

PURPOSE: Liver ischemia-reperfusion injury is a phenomenon presents in events like liver resections and transplantation. The restoration of blood flow may leads to local and systemic injury. Several techniques have been developed in order to avoid or ameliorate ischemia-reperfusion injury in clinical situations. The application of a sttuter reperfusion after the ischemic event (postconditioning) could alters the hydrodynamics and stimulates endogenous mechanisms that attenuate the reperfusion injury. The present study was designed to evaluate the potential protective effect of postconditioning in a model of ischemia-reperfusion in rats. METHODS: Hepatic anterior pedicle of median and left anterolateral segments were exposed and clamped for 1 hour. Two hours later, clamp was released in two different ways: Control Group (n=7): clamp was release straightforward; Postconditioning Group (n=7): clamp was released intermittently. Lipid peroxidation (malondialdehyde) and expression of the glutathione-s-transferase-α-3 gene were studied. RESULTS: Lipid peroxidation was significantly decreased in ischemic and non-ischemic liver by postconditioning. GST- α3 gene was overexpressed in postconditioned group, but not significantly. CONCLUSION: Postconditioning induced hepatoprotection by reducing lipid peroxidation in the ischemic and non-ischemic liver.