The protective effect of Ganoderma lucidum on testicular torsion/detorsion-induced ischemia-reperfusion (I/R) injury

Abstract Purpose To investigate the protective effect of Ganoderma lucidum on testicular torsion/detorsion (T/D)-induced ischemia-reperfusion (I/R) injury. Methods Thirty male Wistar albino rats were randomly categorized into 3 groups: Group 1: sham, Group 2 ( T/D): 2,5 hours of ischemia and 7 days of reperfusion, Group 3 (T/D+ G. lucidum ): 2,5 hours of ischemia and 7 days of reperfusion and 7 days of 20 mg/kg via gastric gavage G. lucidum polysaccharides per day. Biochemical assays of Malondialdehyde (MDA), superoxide dismutase (SOD), Catalase (CAT), Glutathione (GSH) levels , histopathology and expression levels of VEGF and Bcl-2 with immunohistochemical methods were examined in testicular tissue. Results G. lucidum treatment was found to have prevented the T/D-induced I/R injury by decreasing MDA levels of the testis. SOD, CAT and GSH activities were decreased in group 2, while they were increased in group 3 (p<0.001) and significant improvement in the tube diameter was observed in group 3. Bcl-2-positive germinal cells were lowered in group 3 compared to the group 2. VEGF expression showed an increase in group 2, whereas it decreased in group 3. Conclusion The antioxidant G. lucidum is thought to induce angiogenesis by reducing the apoptotic effect in testicular torsion-detorsion.

The role of the exogenous supply of adenosine triphosphate in the expression of Bax and Bcl2L1 genes in intestinal ischemia and reperfusion in rats

Abstract Purpose: To investigate the role of the exogenous supply of adenosine triphosphate (ATP) in the expression of Bax and Bcl2L1 genes in intestinal ischemia and reperfusion (IR) in rats. Methods: The study was designed as a randomized controlled trial with a blinded assessment of the outcome. Eighteen adult male Wistar-EPM1 rats were housed under controlled temperature and light conditions (22-23°C, 12 h light/dark cycle). The animals were randomly divided into 3 groups: 1. Sham group (SG): no clamping of the superior mesenteric artery; 2. Ischemia and reperfusion group (IRG): 3. Ischemia and reperfusion plus ATP (IRG + ATP). ATP was injected in the femoral vein before and after ischemia. Afterwards, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. Results: ATP promoted the upregulation of Bcl2L1 gene expression, whereas it did not have significant effects on Bax gene expression. In addition, the relation of Bax/Bcl2L1 gene expression in the IRG group was 1.39, whereas it was 0.43 in the IRG + ATP group. Bcl2L1 plays a crucial role in protecting against intestinal apoptosis after ischemia and reperfusion. Increased Bcl2L1 expression can inhibit apoptosis while decreased Bcl2L1 expression can trigger apoptosis. Conclusion: Adenosine triphosphate was associated with antiapoptotic effects on the rat intestine ischemia and reperfusion by upregulating of Bcl2L1 gene expression.

Topical hepatic hypothermia associated with ischemic preconditioning. Histopathological and biochemical analysis of ischemia reperfusion damage in a 24 hour model

Abstract Purpose: To develop a new 24 hour extended liver ischemia and reperfusion (LIR) model analyzing the late biochemical and histopathological results of the isolated and combined application of recognized hepatoprotective mechanisms. In addition, we used a new stratification with zoning to classify the histological lesion. Methods: A modified animal model of severe hepatic damage produced through 90 minutes of segmental ischemia (70% of the organ) and posterior observation for 24 hours of reperfusion, submitted to ischemic preconditioning (IPC) and topical hypothermia (TH) at 26ºC, in isolation or in combination, during the procedure. Data from intraoperative biometric parameters, besides of late biochemical markers and histopathological findings, both at 24 hours evolution time, were compared with control (C) and normothermic ischemia (NI) groups. Results: All groups were homogeneous with respect to intraoperative physiological parameters. There were no losses once the model was stablished. Animals subjected to NI and IPC had worse biochemical (gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, direct bilirubin, and total bilirubin) and histopathological scores (modified Suzuki score) compared to those of control groups and groups with isolated or associated TH (p < 0.05). Conclusion: The new extended model demonstrates liver ischemia and reperfusion at 24 hour of evolution and, in this extreme scenario, only the groups subjected to topical hypothermia, combined with ischemic preconditioning or alone, had better outcomes than those subjected to only ischemic preconditioning and normothermic ischemia, reaching similar biochemical and histopathological scores to those of the control group.

Protective effect and mechanism of Lactobacillus on cerebral ischemia reperfusion injury in rats

The present study was designed to investigate the protective effects and mechanism of inactivated lactobacillus (ILA) on cerebral ischemia reperfusion injury (CIRI) in rats. In this experiment, 30 male Sprague Dawley rats were randomly divided into control group, IRI groups, and ILA group. A middle cerebral artery occlusion and reperfusion model was prepared. The rats were killed after 24 hours of recovery of blood flow of cerebral ischemia resulting from 60-min occlusion. The cerebral infarction volume and neurological scores were assayed by staining and behavioral observation. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were assayed by biochemical kits. Cell apoptosis was assayed by Tunnel and the Toll-like receptor (TLR)-4, IkB, and A20 were assayed by western blot. The neurobehavioral scores in IRI rats were significantly lower compared to the control group while ILA improved the neurobehavioral scores of the ILA groups. The cerebral infarction volume and neural cell apoptosis of rats in the ILA groups decreased significantly compared with those in the IRI group. In addition, MDA level in the ILA groups decreased whereas SOD activity increased compared to the IRI group. Moreover, ILA also inhibited the expression of TLR-4 and promoted the expression of IkB and A20. ILA inhibited the apoptosis of neural cells, decreased cerebral infarction volume, and reduced oxidative stress through inhibition of TLR-4/NF-kappa B signaling, improving neurobehavioral scores. Thus from the present study it was concluded that ILA has protective effect on CIRI.

Effect of mild hypothermia on renal ischemia/reperfusion injury after cardiopulmonary resuscitation in a swine model

Abstract Purpose: To investigate the effect of intravascular cooling on renal function after resuscitation. Methods: Twenty four pigs were randomized into three groups (n=8 in each group): therapeutic hypothermia group (TH group), normothermia group (NH group) and sham operation group (SHAM group). After 6 minutes of untreated VF, CPR was performed. Upon ROSC, the TH group received the intravascular cooling. The NH and SHAM group did not undergo therapeutic hypothermia. Haemodynamic parameters were recorded. The bloods were analyzed for serum creatinine (sCr), CysC and NGAL. The kidney was surgically removed observe pathologic changes under a light microscope. Results: The sCr increased in both TH and NH groups after ROSC, compared to baseline. Between two groups, the sCr and creatinine clearance (Cc) showed lower level in the TH group. The urine volume per hour in the TH group were higher during cooling. After resuscitation, NGAL and CysC in the NH group were higher than in the TH group. Under the light microscope, compared with the TH group, the renal injury was prominent in the NH group. Conclusion: Mild hypothermia had a protection to renal ischemia reperfusion injury after resuscitation.

Low-energy shock wave preconditioning reduces renal ischemic reperfusion injury caused by renal artery occlusion

Abstract Purpose: To evaluate whether low energy shock wave preconditioning could reduce renal ischemic reperfusion injury caused by renal artery occlusion. Methods: The right kidneys of 64 male Sprague Dawley rats were removed to establish an isolated kidney model. The rats were then divided into four treatment groups: Group 1 was the sham treatment group; Group 2, received only low-energy (12 kv, 1 Hz, 200 times) shock wave preconditioning; Group 3 received the same low-energy shock wave preconditioning as Group 2, and then the left renal artery was occluded for 45 minutes; and Group 4 had the left renal artery occluded for 45 minutes. At 24 hours and one-week time points after reperfusion, serum inducible nitric oxide synthase (iNOS), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), creatinine (Cr), and cystatin C (Cys C) levels were measured, malondialdehyde (MDA) in kidney tissue was detected, and changes in nephric morphology were evaluated by light and electron microscopy. Results: Twenty-four hours after reperfusion, serum iNOS, NGAL, Cr, Cys C, and MDA levels in Group 3 were significantly lower than those in Group 4; light and electron microscopy showed that the renal tissue injury in Group 3 was significantly lighter than that in Group 4. One week after reperfusion, serum NGAL, KIM-1, and Cys C levels in Group 3 were significantly lower than those in Group 4. Conclusion: Low-energy shock wave preconditioning can reduce renal ischemic reperfusion injury caused by renal artery occlusion in an isolated kidney rat model.

Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the P38-MAPK/TXNIP signaling activation in streptozotocin induced diabetic rats

Abstract Purpose: To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Methods: Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion. In Group DI/R-DEX, 50 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia. Renal function, histology, apoptosis, the levels of TNF-α, IL-1β, and oxidative stress in diabetic kidney were determined. Moreover, expression of P38 mitogen-activated protein kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin-interacting protein (TXNIP) were assessed. Results: The degree of renal I/R injury was significantly increased in DI/R group compared with S group and DS group. The levels of TNF-α, IL-1β, oxidative stress and apoptosis were found significantly higher in DI/R Group when compared with S Group and DS Group. The protein expression of p-P38-MAPK and TXNIP were significantly increased after I/R. All these changes were reversed by DEX treatment. Conclusion: The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.

Tourniquet-induced ischaemia-reperfusion injury: the comparison of antioxidative effects of small-dose propofol and ketamine / Lesão de isquemia-reperfusão induzida por torniquete: comparação dos efeitos antioxidantes de propofol e cetamina em doses baixas

Abstract Objectives: The aim of the present study was to investigate the preventive effects of propofol and ketamine as small dose sedation during spinal anaesthesia on tourniquet-induced ischaemia-reperfusion injury. Methods: 30 patients were randomly assigned into two groups of 15 patients. In the propofol group, sedation was performed with propofol 0.2 mg·kg-1 followed by infusion at a rate of 2 mg·kg-1·h-1. In the ketamine group, a continuous infusion of ketamine 0.5 mg·kg-1·h-1 was used until the end of surgery. Intravenous administration of midazolam was not used in any patients. Ramsay sedation scale was used for assessing the sedation level. Venous blood samples were obtained before propofol and ketamine infusion (T1), at 30 minutes (min) of tourniquet ischaemia (T2), and 5 min after tourniquet deflation (T3) for malondialdehyde (MDA) measurements. Results: No differences were noted between the groups in haemodynamic (p > 0.05) and demographic data (p > 0.05). There was no statistically significant difference between the two groups in terms of T1, T2 and T3 periods (p > 0.05). There was a statistically increase observed in MDA values respectively both in Group P and Group K between the reperfusion period (1.95 ± 0.59, 2.31 ± 0.48) and pre-ischaemia (1.41 ± 0.38, 1.54 ± 0.45), and ischaemia (1.76 ± 0.70, 1.71 ± 0.38) (µmoL-1) periods (p < 0.05). Conclusions: Small-dose propofol and ketamine has similar potential to reduce the oxidative stress caused by tourniquet-induced ischaemia-reperfusion injury in patients undergoing arthroscopic knee surgery under spinal anaesthesia.

Resumo Objetivos: O objetivo do presente estudo foi investigar os efeitos preventivos de propofol e cetamina em sedação com doses baixas durante a raquianestesia sobre lesão de isquemia-reperfusão induzida por torniquete. Métodos: 30 pacientes foram randomicamente alocados em dois grupos de 15 pacientes cada. No grupo propofol, a sedação foi feita com 0,2 mg.kg-1 de propofol seguida por infusão a uma taxa de 2 mg.kg-1.h-1. No grupo cetamina, uma infusão contínua de 0,5 mg.kg-1.h-1 de cetamina foi usada até o final da cirurgia. Midazolam intravenoso não foi administrado em nenhum dos pacientes. A Escala de Sedação de Ramsay (ESR) foi usada para avaliar o nível de sedação. Amostras de sangue venoso foram colhidas antes da administração de propofol e infusão de cetamina (T1), aos 30 minutos (min) de isquemia do torniquete (T2) e 5 min após a desinsuflação do torniquete (T3), para medir os valores de malondialdeído (MDA). Resultados: Não observamos diferenças entre os grupos em relação à hemodinâmica (p > 0,05) e dados demográficos (p > 0,05). Não houve diferença estatisticamente significativa entre os dois grupos nos períodos T1, T2 e T3 (p > 0,05). Um aumento estatisticamente significativo foi observado nos valores de MDA, respectivamente, no Grupo P e Grupo C entre os períodos de reperfusão (1,95 ± 0,59, 2,31 ± 0,48) e pré-isquemia (1,41 ± 0,38, 1,54 ± 0,45) e isquemia (1,76 ± 0,70, 1,71 ± 0,38) (µmoL-1) (p < 0,05). Conclusões: Propofol e cetamina em doses baixas apresentam potencial semelhante para reduzir o estresse oxidativo causado pela lesão de isquemia-reperfusão induzida por torniquete em pacientes submetidos à artroscopia de joelho sob raquianestesia.

On vascular stenosis, restenosis and mannose binding lectin / Acerca de estenose vascular, re-estenose e lectina ligadora da manose

Mannose binding lectin is a lectin instrumental in the innate immunity. It recognizes carbohydrate patterns found on the surface of a large number of pathogenic micro-organisms, activating the complement system. However, this protein seems to increase the tissue damage after ischemia. In this paper is reviewed some aspects of harmful role of the mannose binding lectin in ischemia/reperfusion injury.

Lectina de ligação à manose é uma lectina instrumental na imunidade inata. Ela reconhece padrões de hidratos de carbono encontrados na superfície de um grande número de microrganismos patogênicos, que ativam o sistema complemento. No entanto, esta proteína parece aumentar o dano tecidual após isquemia. Neste trabalho são revisados alguns aspectos do papel nocivo da lectina de ligação à manose na lesão de isquemia/reperfusão.

Analysis of the effects of topical renal hypothermia on lung tissue after kidney ischemia and reperfusion in rats

PURPOSE: To evaluate whether topical renal hypothermia (TRH) at different levels of temperature has protective effects on lung tissue after renal I/R, through an analysis of organ histology and inflammatory markers in lung tissue. METHODS: Twenty-eight male Wistar rats were randomly allocated across four groups and subjected to renal ischemia at different levels of topical renal temperature: normothermia (no cooling, 37°C), mild hypothermia (26°C), moderate hypothermia (15°C), and deep hypothermia (4°C). To induce I/R, the vessels supplying the left kidney of each animal were clamped for 40 minutes, followed by reperfusion. After four hours, another procedure was performed to harvest the tissues of interest. TNF-α, IL-1β and myeloperoxidase activity were measured in lung tissue. Histological analysis was performed in hematoxylin and eosin-stained lung specimens. RESULTS: Induction of renal I/R under deep topical hypothermia resulted in a significant decrease in lung concentrations of TNF-α compared with normothermic I/R (p<0.05). A trend toward significant correlation was found between lung IL-1β concentration and intensity of hypothermia (Spearman r=−0.37; p=0.055). No difference was found in myeloperoxidase activity or histologic injury between groups. CONCLUSION: Topical renal hypothermia reduces activation of the inflammatory cascade in the lung parenchyma. However, tissue-protective effects were not observed. .

Role of Nitric Oxide During Liver Transplantation.

Nitric oxide (NO) is a gaseous molecule produced from Nitric Oxide Synthases (NOS) enzyme. Three isoforms of NOS have been observed: endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS). All three of these isoforms are expressed in liver in varying spatial and temporal ways. In liver, both nNOS and eNOS maintain homeostasis. Whereas iNOS is not expressed constitutively in liver, but rather is expressed in most liver cell types given the appropriate stimulatory conditions. Conflicting results have been observed on the behaviour and possible roles of the NO in several models of ischemia/ reperfusion injury during liver transplantation. Indeed, endogenous NO production has been associated with either protective or cytotoxic effects. Thus some, not all studies suggest that although eNOSderived NO production is protective in ischemia/reperfusion, iNOS derived NO production may contribute to ischemia/ reperfusion injury. This review article focuses on possible role of NO in liver transplantation.

Mesenteric lymph reperfusion exacerbates spleen injury caused by superior mesenteric artery occlusion shock

The intestinal lymph pathway plays an important role in the pathogenesis of organ injury following superior mesenteric artery occlusion (SMAO) shock. We hypothesized that mesenteric lymph reperfusion (MLR) is a major cause of spleen injury after SMAO shock. To test this hypothesis, SMAO shock was induced in Wistar rats by clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h. Similarly, MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h, followed by reperfusion for 2 h. In the MLR+SMAO group rats, both the SMA and MLD were clamped and then released for reperfusion for 2 h. SMAO shock alone elicited: 1) splenic structure injury, 2) increased levels of malondialdehyde, nitric oxide (NO), intercellular adhesion molecule-1, endotoxin, lipopolysaccharide receptor (CD14), lipopolysaccharide-binding protein, and tumor necrosis factor-α, 3) enhanced activities of NO synthase and myeloperoxidase, and 4) decreased activities of superoxide dismutase and ATPase. MLR following SMAO shock further aggravated these deleterious effects. We conclude that MLR exacerbates spleen injury caused by SMAO shock, which itself is associated with oxidative stress, excessive release of NO, recruitment of polymorphonuclear neutrophils, endotoxin translocation, and enhanced inflammatory responses.

The role of serum lactate in post-cardiac arrest syndrome

Cardiopulmonary arrest is a medical emergency with significant mortality. The success of resuscitation led to the emergence of post-cardiac arrest syndrome (PCAS), which originates from ischemia-reperfusion injury and its consequent increase in serum lactate. Despite the robust evidence correlating hyperlactatemia as a prognostic marker in critically ill patients, there is insufficient evidence about the role of serum lactate in the outcome of PCAS. Thus, the purpose of this review is to check the current evidence on the role of lactate in predicting mortality in PCAS.

Protective effect of N-acetylcysteine on kidney as a remote organ after skeletal muscle ischemia-reperfusion / Efeito protetor da N-acetilcisteína no rim como um órgão remoto músculo esquelético após isquemia-reperfusão

PURPOSE: To investigate whether N-acetylcysteine has a protective effect against renal injury as a remote organ after skeletal muscle ischemia-reperfusion in rats. METHODS: Twenty Wistar male rats were divided randomly into two experimental groups: group ischemia-reperfusion (group I) and group ischemia-reperfusion + N-acetylcysteine (group II). After ketamine and xylazine anesthesia, femoral artery was exposed. All animals were undergone 2h of ischemia by occlusion femoral artery and 24h of reperfusion. Rats that were treated with N-acetylcysteine given IV at a dose of 150 mg/kg-¹, immediately before reperfusion. After 24h of reperfusion, the blood samples were collected and submitted for evaluation of plasmatic urea, creatinine values and then rats were euthanized and left kidney harvested for histopathological analysis under light microscopy. RESULTS: The urea (35±7.84 mg.dL-1), creatinine (1.46±0.47 mg.dL-1) values were significantly lower in group II (P=0.000). Renal histopathologic study in group I showed extensive distal and proximal tubular cells necrosis and sloughing of epithelial cells into the tubular lumen, cast formation in tubule and glomerul, glomerul fibrosis and hemorrhage. Histopathologically, there was a significant difference (p=0.037) between two groups. CONCLUSION: The N-acetylcysteine was able to decrease renal injury induced by skeletal muscle ischemia reperfusion in rats.

OBJETIVO: Investigar se a N-acetilcisteína tem um efeito protetor contra a lesão renal como um órgão remoto músculo esquelético após isquemia-reperfusão em ratos. MÉTODOS: Vinte ratos Wistar machos foram distribuídos aleatoriamente em dois grupos experimentais: grupo isquemia-reperfusão (grupo I) e grupo isquemia-reperfusão N-acetilcisteína (grupo II). Após a anestesia de ketamina e xilazina, a artéria femoral foi exposta. Todos os animais foram submetidos a 2h de isquemia pela oclusão da artéria femoral e 24h de reperfusão. Os ratos que foram tratados com N-acetilcisteína administrados IV na dose de 150 mgkg-1, imediatamente antes da reperfusão. Após 24h de reperfusão, as amostras de sangue foram coletadas e submetidas para avaliação de uréia, creatinina e, em seguida, os ratos foram sacrificados e rim esquerdo retirados para estudo histopatológico em microscopia de luz. RESULTADOS: A uréia (35 ± 7,84 mg.dL-1), creatinina (1,46 ± 0,47 mg.dL-1) os valores foram significativamente menores no grupo II (p=0,000). Estudo histopatológico renal do grupo I mostrou extensa necrose distal e proximal, células tubular e descamação das células epiteliais para o lúmen tubular, formação de elenco no túbulo e glomerulo, fibrose glomerular e hemorragia. Histopatologicamente houve uma diferença significativa (p=0,037) entre os dois grupos. CONCLUSÃO: A N-acetilcisteína foi capaz de diminuir a lesão renal induzida por reperfusão de isquemia do músculo esquelético em ratos.

Lesão de isquemia e reperfusão após clampagem contínua ou intermitente do pedículo hepático em coelhos / Ischemia/reperfusion injury after continuous or intermittent hepatic pedicle clamping in rabbits

RACIONAL: O controle do sangramento na hepatectomia é um desafio para os cirurgiões. A clampagem do pedículo hepático é manobra cirúrgica que pode promover redução do sangramento, mas provoca isquemia hepatocelular. Isso, junto com a reperfusão depois que a clampagem termina, leva à lesão de isquemia e reperfusão. OBJETIVO: Examinar os efeitos da lesão de isquemia e reperfusão no fígado após clampagem contínua e intermitente do pedículo hepático, usando a quantificação de apoptose como ferramenta. MÉTODO: Vinte coelhos New Zealand foram divididos em grupos 1 (controle), 2 (60 minutos de isquemia contínua) e 3 (60 minutos de isquemia intermitente alternando 12 minutos de isquemia e três minutos de reperfusão). Biópsias hepáticas foram colhidas antes e ao fim da isquemia e após seis horas de reperfusão, quando os animais eram sacrificados. Os fragmentos obtidos foram submetidos à análise histológica e histoquímica (reação de Tunel). Campos microscópicos foram analisados para caracterização e quantificação de apoptose. RESULTADOS: A isquemia levou à elevação do índice apoptótico em ambos os grupos experimentais em relação aos controles, mas similar entre eles. Depois da reperfusão os índices voltaram aos valores iniciais. CONCLUSÃO: A clampagem do pedículo hepático, tanto contínua quanto intermitente, induz a apoptose em células hepáticas de modo igual.

BACKGROUND : The control of bleeding in hepatectomy is a challenge for surgeons. The hepatic pedicle clamping is a surgical maneuver that can provide reduction in bleeding, but it provokes a hepatocellular suffering. This, along with reperfusion after the clamping finishes, leads to an injury known as ischemia/reperfusion injury. AIM: To examine the effects of the ischemia/reperfusion injury on the liver after continuous and intermittent hepatic pedicle clamping in an animal model, using the quantification of apoptosis for evaluation. METHOD: Twenty New Zealand rabbits were assigned to groups 1 (control), 2 (60 minutes of continuous ischemia) and 3 (60 minutes of intermittent ischemia alternating 12 minutes of ischemia and three minutes of reperfusion). Liver biopsies were collected before ischemia, at its end and after six hours of reperfusion, when the animals were killed. The liver fragments were subjected to histological analysis (paraffinization and hematoxilin-eosin staining) and histochemical (Tunel reaction). Microscope fields of view were scanned for characterization and quantification of apoptosis. RESULTS : Ischemia led to an increased apoptotic index in both experimental groups in comparison to controls, but similarly between them. After the reperfusion, the indexes returned to baseline values. CONCLUSION: Clamping of the hepatic pedicle, either continuous or intermittent, induces apoptosis in liver cells in a similar way.

Reperfusão rápida e homogênea como fator de risco da síndrome pós-reperfusão hepática durante transplante ortotópico de fígado / Rapid and homogeneous reperfusion as a risk factor for postreperfusion syndrome during orthotopic liver transplantation / Reperfusión rápida y homogénea como factor de riesgo del síndrome postreperfusión hepática durante transplante ortotópico de hígado

JUSTIFICATIVA E OBJETIVOS: A revascularização do órgão transplantado é um momento crucial no transplante ortotópico de fígado (TOF). Aproximadamente um terço dos pacientes desenvolve síndrome pós-reperfusão hepática (SPR), uma combinação de hipotermia, desordens metabólicas e instabilidade cardiovascular que podem levar à parada cardíaca. O objetivo deste estudo foi avaliar a relação velocidade-qualidade (RVQ) da reperfusão do órgão transplantado como fator independente de predição da SPR. MÉTODOS: Todos os pacientes elegíveis que se submeteram ao TOF em nossa instituição de 1987 a março de 2009 foram incluídos. O OR ajustado da associação RVQ-SPR foi obtido através do modelo de regressão logística, incluindo oito variáveis de confusão. RESULTADOS: A proporção de pacientes que desenvolveram SPR foi maior nos pacientes com RVQ identificada como boa (75,8 por cento) do que naqueles com RVQ média ou baixa; o risco relativo ao comparar a RVQ de boa qualidade com a RVQ de baixa qualidade foi de 12,9 (IC 95 por cento: 2,1 - 528,8). O OR ajustado foi de 132,9 (IC 95 por cento: 10,5 - 1688,6) quando a RVQ de boa e baixa qualidade foram comparadas e de 90,9 (IC 95 por cento: 13,8-645,2) comparando a RVQ boa com a intermediária. CONCLUSÕES: De acordo com nossos resultados, a RVQ pode ser considerada um bom fator preditivo da SPR.

BACKGROUND AND OBJECTIVES: The revascularization of the graft remains as a crucial instant of the orthotopic liver transplantation (OLT) surgical procedure. About a third of the recipients suffer the postreperfusion syndrome (PRS), a combination of hypothermia, metabolic disorders and cardiovascular instability potentially leading to cardiac arrest. The objective of this study was to evaluate the speed-quality (SQR) of the graft`s reperfusion as an independent predictor of PRS. METHODS: All eligible patients receiving an OLT in our institution from 1987 to march 2009 were included. The adjusted OR for SQR-PRS association was obtained by means of logistic regression modeling including eight potential confounders. RESULTS: The proportion of recipients suffering PRS was highest when the SQR was identified as good (75.8 percent) compared to those with middle or poor SQR; the relative risk comparing good SQR with poor SQR was 12.9 (CI 95 percent: 2.1-528.8). The adjusted OR was 132.9 (95 percent CI: 10.5-1688.6) when comparing good with bad SQR and 90.9 (95 percent CI: 13.8-645.2) when comparing good with intermediate SQR. CONCLUSIONS: According to our results, SQR can be considered an unambiguous predictor of PRS.

JUSTIFICATIVA Y OBJETIVOS: La revascularización del órgano transplantado es un momento crucial en el transplante ortotópico de hígado (TOH). Aproximadamente un tercio de los pacientes debuta con síndrome de post-reperfusión hepática (SPR), una combinación de hipotermia, desórdenes metabólicos e inestabilidad cardiovascular que pueden conllevar a la parada cardíaca. El objetivo de este estudio fue evaluar la relación velocidad-calidad (RVC), de la reperfusión del órgano transplantado como factor independiente de predicción de la SPR. MÉTODOS: Todos los pacientes elegibles que se sometieron al TOH en nuestra institución desde 1987 a marzo de 2009, estuvieron incluidos en el estudio. El OR ajustado de la asociación RVC-SPR, se obtuvo a través del modelo de regresión logística, incluyendo ocho variables de confusión. RESULTADOS: La proporción de pacientes que debutaron con SPR fue más elevada en los pacientes con RVC identificada como buena (75,8 por ciento), que en aquellos con RVC media o baja; el riesgo relativo al comparar la RVC de buena calidad con la RVC de baja calidad fue de 12,9 (IC 95 por ciento: 2,1 - 528,8). El OR ajustado fue de 132,9 (IC 95 por ciento: 10,5 - 1688,6) cuando la RVC de buena y baja calidad fueron comparadas, y de 90,9 (IC 95 por ciento: 13,8-645,2) comparando la RVC buena con la intermedia. CONCLUSIONES: De acuerdo con nuestros resultados, la RVC puede ser considerada como un buen factor predictivo de la SPR.

Papel do exercício físico na isquemia/reperfusão pulmonar e resposta inflamatória: [revisão] / Role of exercise training on pulmonary ischemia/reperfusion and inflammatory response: [review]

O avanço tecnológico associado aos novos conhecimentos científicos tem proporcionado melhora na prevenção e/ou tratamento das complicações cardiorrespiratórias advindas de cirurgias cardiotorácicas e procedimentos envolvendo isquemia/reperfusão (IR), mas os riscos destes procedimentos ainda permanecem altos. Assim, medidas profiláticas que possam reduzir o aparecimento das complicações pós-cirúrgicas em pacientes devem ser investigadas. O exercício físico aeróbio de moderada intensidade tem sido recomendado como terapia não farmacológica tanto na prevenção como no tratamento de diversas doenças cardiovasculares e endócrino-metabólicas. Assim, o objetivo desse trabalho foi realizar uma revisão de literatura sobre os mecanismos pelos quais o processo de IR pulmonar promove lesão local e sistêmica de órgãos, e o papel dos mediadores inflamatórios na IR pulmonar. Além disso, essa revisão abordará a influência do exercício físico moderado como abordagem profilática nas complicações advindas da IR pulmonar. Essa revisão evidencia a escassez de trabalhos na área e a necessidade de maiores estudos enfocando o preparo físico dos pacientes a serem submetidos à cirurgia cardiotorácica. Trabalhos pioneiros foram desenvolvidos em modelos animais, demonstrando a importância do exercício físico na redução da resposta inflamatória induzida pelo procedimento de IR pulmonar. Conclui-se que o preparo pré-cirúrgico dos pacientes deve envolver equipe multidisciplinar da área de saúde, com inclusão de profissional de educação física, para que a prescrição do exercício físico seja individualizada e supervisionada. Além disso, esse preparo pré-cirúrgico poderá propiciar redução das complicações advindas do processo operatório, redução do período de internação hospitalar e, consequentemente, melhora na recuperação do paciente, acarretando ainda menores gastos para o sistema de saúde. Foram utilizadas como referências publicações em inglês e português de artigos...

Advances in new technologies associated with improvement of knowledge in medicine have promoted important development in therapeutic and preventive approaches in an attempt to diminish complications following cardiothoracic process involving ischemia/ reperfusion (IR). Nevertheless, postoperative pulmonary injuries remain high and are considered one of the most frequent complications after cardiothoracic surgery. Thus, new strategies with prophylactic actions are crucial in cardiovascular area in an attempt to reduce complications and to improve patient life. It is well documented that exercise training is a non-pharmacological tool to prevent and/or treat cardiovascular and endocrine-metabolic diseases. The aim of this review was to provide an update of several studies pulmonary IR process and its local and systemic complications and the role of inflammatory response. Furthermore, this review focused on the effects of exercise training on the pulmonary IR as an important strategy to diminish its complications. This review shows that few studies exist regarding the health-promoting physical exercise in cardiothoracic surgery and how important is necessary to increase studies in this area. Recently, studies from our laboratory showed beneficial effects of exercise training in experimental model of pulmonary IR. Collectively, data show that physical preconditioning for patients is very important approach to reduce postsurgical complications as well as diminish the time of hospitalization which includes a specialized personal trainer in the health team. Moreover, this preventive strategy might improve patient recovery and would lead to consuming less resources of the health care system. This review included experimental studies in English and Portuguese found in SciELO and MEDLINE (from 1987 to 2008) and also classics texts related to the title.

Hyperbaric oxygen therapy aggravates liver reperfusion injury in rats / Oxigenoterapia hiperbárica agrava lesão de reperfusão hepática em ratos

PURPOSE: To evaluate the effects of hyperbaric oxygen (HO) therapy in the protection against liver ischemia/reperfusion injury. METHODS: Thirty-two male Wistar rats were divided into four groups of eight animals each: group A - laparotomy and liver manipulation, group B - liver ischemia and reperfusion, group C - HO pretreatment for 60 min followed by liver ischemia and reperfusion, and group D - pretreatment with ambient air at 2.5 absolute atmospheres for 60 min followed by liver ischemia and reperfusion. Plasma was assayed for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). Intra-arterial blood pressure was monitored continuously. Myeloperoxidase activity in the liver and lung was assessed 30 min after reperfusion. RESULTS: Plasma AST, ALT and LDH increased after reperfusion in all animals. Plasma ALT values and myeloperoxidase activity in the liver parenchyma were higher in HO-pretreated animals than in groups A, B and D. HO had a negative hemodynamic effect during liver reperfusion. CONCLUSION: Liver preconditioning with hyperbaric oxygen therapy aggravated liver ischemia/reperfusion injury in rats as demonstrated by plasma ALT and liver myeloperoxidase activity.

OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (OH) como método preventivo da lesão de isquemia e reperfusão (LIR) do fígado. MÉTODOS: Trinta e dois ratos machos Wistar foram distribuídos em quatro grupos de oito animais cada: A - laparotomia e manipulação hepática, B - isquemia e reperfusão hepática, C - pré-tratamento com OH por 60 minutos seguido de isquemia e reperfusão hepática e D - pré-tratamento com ar ambiente a 2,5 atmosferas absolutas por 60 minuto e isquemia e reperfusão hepática. Dosagens seriadas de AST, ALT e DHL foram realizadas. A pressão intra arterial foi monitorizada continuamente. O grau de infiltração leucocitária no fígado e pulmões foi inferido pela dosagem de mieloperoxidade tecidual. RESULTADOS: O nível sérico de AST, ALT e DHL aumentou em todos animais. Os animais expostos a OH apresentaram níveis de ALT e infiltração leucocitária hepática maior que os demais. A OH apresentou efeitos hemodinâmicos negativos durante a reperfusão hepática. CONCLUSÃO: O pré-condicionamento hepático por oxigenoteraia hiperbárica agrava a lesão de isquemia e reperfusão hepática em ratos.

Protective effect of pifithrin-alpha on brain ischemic reperfusion injury induced by bilateral common carotid arteries occlusion in gerbils.

Involvement of p53 has been implicated in apoptosis induced cell death in ischemic reperfusion injury. In the present study, we have investigated neuroprotective potential of pifithrin-alpha, a p53 inhibitor in bilateral common carotid arteries occlusion (5 min) model of global cerebral ischemia in Mongolian gerbils. Gerbils were treated with pifithrin-alpha 3 mg/kg, ip. 30 min prior to occlusion. There was a significant increase in neurological symptoms and locomotor activity in ischemic animals as compared with the sham-operated animals. Increase in neurological symptoms and locomotor activity was attenuated by pifithrin-alpha 3 mg/ kg, ip. Significant increase in the number of the surviving neurons in the hippocampal CA1 pyramidal region was observed in ischemic animals treated with pifithrin-alpha 3 mg/kg, ip. This study demonstrates the neuroprotective effect of pifithrin-alpha in global cerebral ischemia in gerbils.

The intestinal tract as the major source of interleukin 6 production during abdominal aortic clamping and hind limb ischaemia-reperfusion injury

PURPOSE: The aim of this study was to investigate whether the hind limbs or intestinal tract is the most important initiator of the inflammatory response secondary aortic clamping and hind limb ischemia/reperfusion injury. METHODS: Blood samples of Wistar rats obtained from posterior cava vein, portal vein, and heart cavity during either laparotomy (control group, n=8) or laparotomy + 2 h of aortic clamping and bilateral hind limb ischemia (ischemia group, n=8), or 2 h after ischemia and 2 h of reperfusion (ischemia-reperfusion group, n=8) were assayed for interleukin 6 (IL-6) and C-reactive protein (CRP). RESULTS: Serum IL-6 at the heart (223.6±197.9 [10-832] pg/mL) was higher (p<0.001) than at both portal (133.08±108.52 [4-372] pg/mL) and posterior cava veins (127.58±109.15 [8-388] pg/mL). CRP was not significant different among groups. CONCLUSION: The splanchnic region is also a source of inflammatory response secondary to ischemia and reperfusion of the hind limbs.

OBJETIVO: Investigar qual o principal mediador da resposta inflamatória na lesao de isquemia/reperfusão após clampeamento da aorta abdominal e isquemia dos membros inferiores: o intestine ou as extremidades inferiores. MÉTODOS: amostra de sangue de ratos Wistar coletados da cava posterior, porta e cavidade cardíaca during tanto laparotomia (grupo controle n=8) ou laparotomia + 2 horas de clampeamento aórtico e isquemia bilateral de membros posteriores (grupo isquemia n=8), ou 2 h de isquemia seguido por 2 horas de reperfusão (grupo isquemia/reperfusão n=8), onde foram dosados interleucina 6 e proteína C-reativa. RESULTADOS: Il-6 no coração (223.6±197.9 [10-832] pg/mL) foi maior (p<0.001) tanto na veia porta (133.08±108.52 [4-372] pg/mL) quanto na veia cava posterior (127.58±109.15 [8-388] pg/mL). PCR não foi significativamente diferente entre os grupos. CONCLUSÃO: o trato intestinal foi responsável pela resposta inflamatória secundária a lesão de isquemia/reperfusão.