Acute Physical Stress Preconditions the Heart Against Ischemia/Reperfusion Injury Through Activation of Sympathetic Nervous System / Estresse Físico Agudo Precondiciona o Coração Contra a Injúria por Isquemia/Reperfusão Através da Ativação do Sistema Nervoso Simpático

Abstract Background: Stress is defined as a complicated state that related to homeostasis disturbances, over-activity of the sympathetic nervous system and hypothalamus-pituitary-adrenal axis responses. Cardiac preconditioning reduces myocardial damages. Objective: This study was designed to assess the cardioprotective effects of acute physical stress against ischemia/reperfusion (I/R) injury through the activation of the sympathetic nervous system. Methods: Thirty-two male Wistar rats were divided into four groups; (1) IR (n = 8): rats underwent I/R, (2) Acute stress (St+IR) (n = 8): physical stress induced 1-hour before I/R, (3) Sympathectomy (Symp+IR) (n = 8): chemical sympathectomy was done 24-hours before I/R and (4) Sympathectomy- physical stress (Symp+St+IR) (n = 8): chemical sympathectomy induced before physical stress and I/R. Chemical sympathectomy was performed using 6-hydroxydopamine (100 mg/kg, sc). Then, the hearts isolated and located in the Langendorff apparatus to induce 30 minutes ischemia followed by 120 minutes reperfusion. The coronary flows, hemodynamic parameters, infarct size, corticosterone level in serum were investigated. P < 0.05 demonstrated significance. Results: Physical stress prior to I/R could improve left ventricular developed pressure (LVDP) and rate product pressure (RPP) of the heart respectively, (63 ± 2 versus 42 ± 1.2, p < 0.05, 70 ± 2 versus 43 ± 2.6, p < 0.05) and reduces infarct size (22.16 ± 1.3 versus 32 ± 1.4, p < 0.05) when compared with the I/R alone. Chemical sympathectomy before physical stress eliminated the protective effect of physical stress on I/R-induced cardiac damages (RPP: 21 ± 6.6 versus 63 ± 2, p < 0.01) (LVDP: 38 ± 4.5 versus 43 ± 2.6, p < 0.01) (infarct size: 35 ± 3.1 versus 22.16 ± 1.3, p < 0.01). Conclusion: Findings indicate that acute physical stress can act as a preconditional stimulator and probably, the presence of sympathetic nervous system is necessary.

Resumo Fundamento: O estresse é definido como um estado complicado de distúrbios da homeostase, hiperatividade do sistema nervoso simpático e das respostas do eixo hipotálamo-hipófise-adrenal. O pré-condicionamento cardíaco diminui os danos do miocárdio. Objetivo: Esse estudo avaliou os efeitos cardioprotetores do estresse físico agudo contra a lesão por isquemia-reperfusão (I/R) através da ativação do sistema nervoso simpático. Métodos: Trinta e dois ratos machos Wistar foram divididos em quatro grupos; (1) IR (n = 8): ratos submetidos a I/R, (2) Estresse agudo (St+IR) (n = 8): estresse físico induzido 1 hora antes da I/R, (3) Simpatectomia (Symp+IR) (n = 8): a simpatectomia química foi realizada 24 horas antes da I/R e (4) Simpatectomia-estresse físico (Symp+St+IR) (n = 8): simpatectomia induzida antes do estresse físico e da I/R. A simpatectomia química foi realizada com 6-hidroxidopamina (100 mg/kg, SC). Em seguida, os corações foram isolados e colocados em aparato de Lagendorff por 30 minutos para induzir isquemia, seguida de reperfusão por 120 minutos. Os fluxos coronarianos, os parâmetros hemodinâmicos, o tamanho do infarto e os níveis de corticosterona plasmática foram investigados. Valores de p < 0,05 foram considerados significativos. Resultados: O estresse físico anterior à I/R pode melhorar a pressão desenvolvida no ventrículo esquerdo (PDVE) e duplo produto (DP), respectivamente, (63 ± 2 versus 42 ± 1,2, p < 0,05, 70 ± 2 versus 43 ± 2,6, p < 0,05) e reduzir o tamanho do infarto (22,16 ± 1,3 versus 32±1,4, p < 0,05) quando comparado com a I/R isoladamente. A simpatectomia química antes do estresse físico eliminou o efeito protetor do estresse físico sobre os danos cardíacos induzidos pela I/R (DP: 21 ± 6,6 versus 63 ± 2, p < 0,01) (PDVE: 38 ± 4,5 versus 43 ± 2,6, p < 0,01) (tamanho do infarto: 35 ± 3,1 versus 22,16 ± 1,3, p < 0,01). Conclusão: Os achados indicam que o estresse físico agudo pode funcionar como um estimulador pré-condicional e, provavelmente, a presença do sistema nervoso simpático é necessária.

Splenic ischemic preconditioning attenuates oxidative stress induced by hepatic ischemia-reperfusion in rats

Abstract Purpose: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. Methods: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. Results: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. Conclusion: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.

Muscle changes with high-intensity aerobic training in an animal model of renal disease

Abstract Purpose: To analyze the muscle changes with high-intensity aerobic training (HIAT) in an animal model of renal disease (RD). Methods: Twenty one adult Wistar rats were divided into 3 groups: healthy sedentary (HS), RD sedentary (RDS), RD aerobic training (RDAT). RDS and RDAT were subjected to unilateral renal ischemia-reperfusion (10 min) and 21days after that, RDAT was subjected to 6 weeks HIAT (swimming). Serum creatinine (Cr) and muscle morphometry (cross-sectional area = CSA) of gastrocnemius were analyzed. Results: Cr was higher (p = 0.0053) in RDS (0.82 ± 0.04) than in the others (RDAT 0.55 ± 0.04; HS 0.55 ± 0.04). Morphometric analysis (class interval of CSA in μm2/absolute frequency of muscle fibers in each class) indicated that 50th percentile occurred in: HS 7th class (3000.00-3499.00/515), RDS, 8th class (3500.00-3999.00/484), RDAT 5th class (2000.00-2499.00/856). CSA of largest fibers in RDS, RDAT, HS was 9953.00 μm2, 9969.00 μm2,11228.00 μm2, respectively. High frequency of fibers with lower CSA occurred in 4th, 5th, 6th and 7th class in RDA, absence of fibers into 22nd, 23rd classes (RDS and RDAT). Conclusion: HIAT in an animal model of RD resulted in increased the number of muscle fibers with smaller CSA.

Liver ischemia and reperfusion injury. Pathophysiology and new horizons in preconditioning and therapy

Abstract It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive ("cheating") strategies, non-pharmacological and pharmacological options to treat the liver IR injury.

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

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.

The role of bradykinin in lung ischemia-reperfusion injury in a rat lung transplantation model

ABSTRACT PURPOSE: To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4. METHODS: Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192). LTx was performed after 18 h cold ischemia time and harvested two days post-LTx. Blood gas analysis (PO2), wet/dry weight ratio (W/D), myeloperoxidase activity (MPO), and lipid peroxidation (MDA) were analyzed at 48 hr after transplantation. Immunohistochemical (IHC) analysis was performed in the same sample and validated by Western-Blot. RESULTS: Compared to the LPD group, the AB192 group showed higher PO2, lower W/D ratio, and decreased MPO and MDA. IHC studies showed strong bradykinin β2 receptor (B2R) staining in the LPD group, especially in inflammatory cells, alveolar macrophages, and respiratory epithelial cells. Expression of B2R by Western-Blot was significantly different between the AB192 and LPD groups. CONCLUSION: Bradykinin may be a competitive substrate of DPP-4, and decreased bradykinin levels may enhance protective effects against ischemia/reperfusion injury during LTx.

Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke / Déficit de memória associado ao aumento dos níveis cerebrais de citocinas pró-inflamatórias e neurodegeneração na isquemia cerebral aguda

The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

O presente estudo teve como objetivo investigar alterações comportamentais e processos inflamatórios na isquemia cerebral induzida pela oclusão unilateral da carótida comum esquerda (UCCAO) em camundongos. As alterações comportamentais foram avaliadas após 15 minutos de isquemia e 24 horas de reperfusão. O teste de reconhecimento de objetos foi utilizado para avaliação da memória e do aprendizado. Em seguida, os animais foram mortos e os encéfalos foram coletados e processados para avaliação das alterações patológicas pelas técnicas de TTC e H&E, assim como da dosagem de mediadores inflamatórios por ELISA. A UCCAO promoveu alterações de memória após a reperfusão. Foram visualizadas áreas de infarto cerebral pela coloração de TTC e cavidades necróticas circundadas por neurônios isquêmicos no cérebro e neurodegeneração hipocampal. A UCCAO causou aumento dos níveis encefálicos de TNF-a, IL-1b e CXCL1. Estes achados demonstraram o envolvimento dos mediadores inflamatórios no sistema nervoso central e da neurodegeneração no déficit cognitivo após isquemia cerebral aguda.

Intra and postoperative evaluations of microcirculation and micro-rheological parameters in a rat model of musculocutaneous flap ischemia-reperfusion

PURPOSE:To examine how the ischemia-reperfusion injury of latissimus dorsi-cutaneous maximus (LDCM) musculocutaneous flap affects the microcirculatory (flap's skin surface) and hemorheological parameters, and whether an intraoperative deterioration would predictively suggest flap failure in the postoperative period.METHODS: Ten healthy male rats were subjected to the study. In Group I the left flap was sutured back after 2-hour, while the contralateral side was right after its elevation. In Group II the same technique was applied, but the pedicle of the left flap was atraumatically clamped for 2-hour. The contralateral side was left intact. On the flap skin surface laser Doppler tissue flowmetry measurements were done before and after and during the protocols applied in the groups. Microcirculatory and hemorheological examinations were done postoperatively.RESULTS: The microcirculatory parameters significantly decreased during immobilization and ischemia. Afterwards, all the regions showed normalization. In the retrospective analysis there was a prominent difference between the microcirculatory parameters of necrotic and survived flap during the early postoperative days (1-3) in Group II. Erythrocyte aggregation and deformability showed only slight differences.CONCLUSIONS: Two-hour ischemia and reperfusion caused deterioration in latissimus dorsi-cutaneous maximus flap microcirculation. Predicting the possible postoperative complication, the intraoperative laser Doppler measurement can be informative.

Ischemia and reperfusion injury in renal transplantation: hemodynamic and immunological paradigms / Lesão de isquemia e reperfusão no transplante renal: paradigmas hemodinâmico e imunológico

Ischemia and reperfusion injury is an inevitable event in renal transplantation. The most important consequences are delayed graft function, longer length of stay, higher hospital costs, high risk of acute rejection, and negative impact of long-term follow-up. Currently, many factors are involved in their pathophysiology and could be classified into two different paradigms for education purposes: hemodynamic and immune. The hemodynamic paradigm is described as the reduction of oxygen delivery due to blood flow interruption, involving many hormone systems, and oxygen-free radicals produced after reperfusion. The immune paradigm has been recently described and involves immune system cells, especially T cells, with a central role in this injury. According to these concepts, new strategies to prevent ischemia and reperfusion injury have been studied, particularly the more physiological forms of storing the kidney, such as the pump machine and the use of antilymphocyte antibody therapy before reperfusion. Pump machine perfusion reduces delayed graft function prevalence and length of stay at hospital, and increases long-term graft survival. The use of antilymphocyte antibody therapy before reperfusion, such as Thymoglobulin™, can reduce the prevalence of delayed graft function and chronic graft dysfunction.

A lesão de isquemia e reperfusão é um evento inevitável no transplante de rim, tendo como consequências retardo na função do enxerto, aumento no tempo de hospitalização e dos custos, aumento no risco de rejeição aguda e potencial impacto negativo na evolução a longo prazo. Atualmente, vários fatores estão implicados na fisiopatologia da lesão de isquemia e reperfusão, podendo ser didaticamente divididos em dois paradigmas: hemodinâmico e imunológico. O paradigma hemodinâmico é classicamente descrito como a privação de oxigênio pela interrupção do fluxo sanguíneo, envolvendo diversos sistemas hormonais e pela produção de radicais livres de oxigênio após a reperfusão. O paradigma imunológico tem sido descrito mais recentemente e envolve as células do sistema imune, sobretudo as células T, como papel fundamental na lesão. De acordo com esses conceitos, novas estratégias de prevenção dos impactos da lesão de isquemia e reperfusão têm sido estudadas, especialmente formas mais fisiológicas de preservação do órgão, como a preservação em máquina de perfusão e o uso de anticorpos depletores de linfócitos antes da reperfusão. A perfusão em máquina reduz a prevalência de retardo na função do enxerto e o tempo de hospitalização, além de melhorar a sobrevida do enxerto a longo prazo. Já o uso de anticorpos depletores de linfócitos, como Timoglobulina®, antes da reperfusão, pode diminuir a prevalência de retardo na função do enxerto e a disfunção crônica do mesmo.

Minimal endoscopic changes in non-erosive reflux disease / Alterações endoscópicas mínimas na doença do refluxo não erosiva

BACKGROUND: Gastroesophageal reflux disease is an increasingly common condition worldwide causing a considerable economic impact. More than half the patients with clinical symptoms of reflux disease display no mucosal erosions on esophagogastroduodenoscopy, making it impossible to confirm the diagnosis without further investigations. AIM: To evaluate the correlation between minimal endoscopic changes on white-light esophagogastroduodenoscopy (carditis, mucosal thickening and invisibility of vessels) and histologic changes observed in distal esophageal biopsies in a sample of patients with symptoms suggestive of reflux disease, and to verify the specificity of these symptoms for non-erosive reflux disease. METHODS: Retrospective, cross-sectional study based on information retrieved from a digital database at a Brazilian hospital for the period March-October, 2012. The sample consisted of previously untreated, non-smoking subjects aged >18 years with symptoms suggestive of reflux disease but no esophageal erosions, submitted to esophagogastroduodenoscopy and distal esophageal biopsy. RESULTS: The final sample included 23 subjects. The most frequently observed change was invisibility of vessels (n=21; 91.3%), followed by mucosal thickening (n=15; 65.2%) and carditis (n=5; 21.7%). The correlation coefficient between each variable and the anatomopathological diagnosis was 0.386 for body mass index, 0.479 for mucosal thickening, -0.116 for invisibility of vessels, 0.306 for carditis and 0.462 for hiatal hernia. CONCLUSION: All patients displayed minimal endoscopic changes on esophagogastroduodenoscopy, but only mucosal thickening revealed a moderately significant correlation with severity of esophagitis, although increased body mass index values and the presence of hiatal hernia were also associated. .

RACIONAL: Doença do refluxo gastroesofágico é condição cada vez mais comum em todo o mundo causando impacto econômico considerável. Mais da metade dos pacientes com sintomas clínicos da doença não apresentam erosões endoscópicas da mucosa, o que torna impossível confirmar o diagnóstico sem outras investigações. OBJETIVO: Avaliar a correlação entre mudanças mínimas endoscópicas em endoscopia digestiva alta de luz branca (cardite, espessamento da mucosa e invisibilidade de vasos) e as alterações histológicas observadas em biópsias distais de uma amostra de pacientes com sintomas sugestivos de doença do refluxo, e para verificar a especificidade desses sintomas para a doença não-erosiva. MÉTODOS: Estudo retrospectivo, transversal, com base em informações obtidas a partir de uma base de dados digital em um hospital brasileiro no período de março/outubro de 2012. A amostra foi composta por indivíduos não tratados previamente, não fumantes, >18 anos, com sintomas sugestivos de doença do refluxo, mas sem erosões esofágicas submetidos à endoscopia digestiva alta e biópsia de esôfago distal. RESULTADOS: A amostra final incluiu 23 indivíduos. A alteração mais frequente foi invisibilidade dos vasos (n=21; 91,3%), seguido por espessamento de mucosa (n=15; 65,2%) e cardite (n=5; 21,7%). O coeficiente de correlação entre cada variável e o diagnóstico anatomopatológico foi 0,386 para o índice de massa corporal, 0,479 para espessamento de mucosa, -0,116 para a invisibilidade de vasos, 0,306 para carditis e 0,462 para hérnia hiatal. CONCLUSÃO: Todos os pacientes apresentaram alterações endoscópicas mínimas, mas apenas espessamento da mucosa revelou correlação moderadamente significativa com a gravidade da esofagite, apesar do aumento dos valores no índice de massa corporal e da presença de hérnia hiatal também estarem associados. .

Idosos vítimas de trauma: doenças preexistentes, medicamentos em uso no domicílio e índices de trauma / Elderly victims of trauma: preexisting conditions, medications taken at home and indexes of trauma / Ancianos víctimas de trauma: condiciones preexistentes, medicamentos tomados en el hogar e índices de trauma

Objetivou-se identificar o perfil sociodemográfico de idosos vítimas de trauma, caracterizar doenças preexistentes e medicamentos utilizados no domicílio; calcular índices de trauma e desfecho clínico. Estudo retrospectivo e exploratório, com a análise de dados secundários de um banco de dados de um hospital geral terciário, entre 2008 e 2010. Foram estudados 131 idosos, média de idade 69,9 anos, 73,3% homens, 55,1% casados, 54,7% aposentados; 65,6% possuíam doenças preexistentes e 48,9% usavam medicamentos no domicílio. Houve representatividade de quedas (31,3%), seguidas por atropelamento (28,2%), com cabeça/pescoço sendo a região mais acometida (59,5%). Prevaleceu o trauma moderado (44,3%), com condições de sobrevida após o evento (80,2%). Houve associação entre mecanismo do trauma e doença preexistente (p=0,01) e entre mecanismo do trauma e sexo (p=0,03). O conhecimento das variáveis envolvidas com idosos vítimas de trauma possibilita aos profissionais de saúde o planejamento de medidas preventivas, visando aprimorar sua assistência.

The objective was to identify the sociodemographic profile of the elderly victims of trauma, to characterize preexisting conditions and medications taken at home, and to calculate indices of trauma and clinical outcomes. This is a retrospective and exploratory analysis from a database of a general hospital between 2008 and 2010. There were studied 131 elderly, mean age 69.9 years, 73.3% male, 55.1% married, 54.7% retired, 65.6% had preexisting conditions and 48.9% used drugs at home. There was a representative number of falls (31.3%), followed by running over (28.2%), with the head/neck region being the most affected (59.5%). Moderate trauma prevailed (44.3%), with conditions of survival after the event (80.2%). There was an association between mechanism of trauma and preexisting disease (p=0.01) and between mechanism of trauma and sex (p=0.03). The knowledge of the variables involved with the elderly victims of trauma enables healthcare professionals to plan preventive measures aimed at improving the assistance. Key words: Aged; Wounds and Injuries; Disease; Drug Utilization.

Se objetivó identificar el perfil sociodemográfico de ancianos víctimas de trauma, caracterizar condiciones preexistentes y medicamentos tomados en casa, y calcular índices de trauma y evolución clínica. Se realizó un análisis retrospectivo y exploratorio de una base de datos de un hospital general terciario entre 2008 y 2010. Se estudiaron 131 ancianos, media of 69,9 años, 73,3% hombres, 55,1% casados, 54,7% jubilados, 65,6% tienen condiciones preexistentes y 48,9% estaban tomando medicación en casa. Hubo representación de las caídas (31,3%), seguido de atropello (28,2%). La región cabeza/cuello fue el más afectado (59,5%). Prevaleció trauma moderado (44,3%), con condiciones de supervivencia después del evento (80,2%). Se observó una asociación entre mecanismo de lo trauma y enfermedad previa (p=0,01) y entre mecanismo de lo trauma y sexo (p=0,03). El conocimiento de las variables que intervienen con ancianos víctimas de trauma permite a los profesionales de la salud planificar medidas preventivas para mejorar su asistencia.

Mesenteric lymph reperfusion after superior mesenteric artery occlusion shock exacerbates endotoxin translocation in brain

PURPOSE: To determine the role of mesenteric lymph reperfusion (MLR) on endotoxin translocation in brain to discuss the mechanism of brain injury subjected to superior mesenteric artery occlusion (SMAO) shock. METHODS: Twenty-four rats were randomly assigned to MLR, SMAO, MLR+SMAO and sham groups. MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h and then allowing reperfusion for 2 h in the MLR group; SMAO involved clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h in the SMAO group; occlusion of both the SMA and MLD for 1 h was followed by reperfusion for 2 h in the MLR+SMAO group rats. RESULTS: SMAO shock induced severe increased levels of the endotoxin, lipopolysaccharide receptor, lipopolysaccharide-binding protein, intercellular adhesion molecule-1 and tumor necrosis factor-α. Concurrently, MLR after SMAO shock further aggravates these deleterious effects. CONCLUSION: Mesenteric lymph reperfusion exacerbated the endotoxin translocation in brain; thereby increased inflammatory response occurred, suggesting that the intestinal lymph pathway plays an important role in the brain injury after superior mesenteric artery occlusion shock. .

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats / Comparação dos efeitos de dexmedetomidina administrada em dois momentos diferentes para lesão de isquemia/reperfusão renal em ratos / Comparación de los efectos de la dexmedetomidina administrada en 2 momentos diferentes para lesión de isquemia-reperfusión renal en ratones

Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5), ischemia reperfusion (IR) (IR group, n = 7), IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7) and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7). In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal) was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN) levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043), although urine flow was significantly higher in group Dex. R (p = 0.003). The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels. .

Justificativa e objetivos: Investigar os efeitos de dexmedetomidina sobre a insuficiência renal isquêmica em ratos. Métodos: No presente estudo, 26 ratos machos adultos, albinos Wistar, com peso 230-300 g, foram randomicamente divididos em quatro grupos: pseudo-operado (n = 5), isquemia-reperfusão (grupo IR, n = 7), IR/tratamento de reperfusão com dexmedetomidina (grupo Dex-R, n = 7) e IR/tratamento pré-isquemia com dexmedetomidina (grupo Dex-I, n = 7). No primeiro grupo, uma pseudo-operação foi feita e clampeamentos renais não foram aplicados. No grupo IR, isquemia renal foi induzida por oclusão das artérias e veias renais bilaterais durante 60minutos seguida por reperfusão durante 24horas. Nos grupos Dex-R e Dex-I, o mesmo procedimento cirúrgico destinado ao grupo IR foi feito e dexmedetomidina (100mcg/kg intraperitoneal) foi administrada cinco minutos após a reperfusão e antes da isquemia. No fim da reperfusão, amostras de sangue foram coletadas, os ratos foram sacrificados e os rins esquerdos processado para histologia. Resultados: Os níveis de nitrogênio ureico no sangue (BUN) dos grupos Dex-R e Dex-I estavam significativamente mais baixos do que os do grupo IR (p = 0,015, p = 0,043), embora o fluxo urinário tenha sido significativamente maior no grupo Dex-R (p = 0,003). O escore histopatológico renal do grupo IR foi significativamente maior do que os dos outros grupos. Não houve diferença significativa entre os grupos Dex-R e Dex-I. Conclusões: Os resultados demonstraram que a administração de dexmedetomidina reduziu histomorfologicamente a lesão de IR renal. A administração de dexmedetomidina durante o período de reperfusão foi considerada como mais eficaz por causa do aumento do débito urinário e da diminuição dos níveis de BUN. .

Justificación y objetivos: investigar los efectos de la dexmedetomidina sobre la insuficiencia renal isquémica en ratones. Métodos: en el presente estudio, 26 ratones machos adultos, albinos Wistar, con un peso de 230-300 g fueron divididos aleatoriamente en 4 grupos: seudooperado (n = 5), isquemia-reperfusión (grupo IR, n = 7), IR/tratamiento de reperfusión con dexmedetomidina (grupo Dex-R, n = 7) e IR/tratamiento preisquemia con dexmedetomidina (grupo Dex-I, n = 7). En el primer grupo, se realizó una seudooperación y no se aplicaron pinzamientos renales. En el grupo IR, la isquemia renal fue inducida por oclusión de las arterias y venas renales bilaterales durante 60 min seguida por reperfusión durante 24 h. En los grupos Dex-R y Dex-I, se llevó a cabo el mismo procedimiento quirúrgico destinado al grupo IR, y la dexmedetomidina (100 µg /kg intraperitoneal) fue administrada 5 min después de la reperfusión y antes de la isquemia. Al final de la reperfusión, fueron recogidas muestras de sangre, los ratones fueron sacrificados y el riñón izquierdo procesado para histología. Resultados: los niveles de nitrógeno ureico en la sangre (BUN) de los grupos Dex-R y Dex-I eran significativamente más bajos que los del grupo IR (p = 0,015; p = 0,043), aunque el flujo urinario era significativamente mayor en el grupo Dex-R (p = 0,003). La puntuación histopatológica renal del grupo IR fue significativamente mayor que la de los otros grupos. No hubo diferencia significativa entre los grupos Dex-R y Dex-I. Conclusiones: los resultados demostraron que la administración de dexmedetomidina redujo histomorfológicamente la lesión de IR renal. La administración de dexmedetomidina durante el período de reperfusión fue considerada más eficaz debido al aumento de producción de orina y a la disminución ...

Effects of ischemic preconditioning and cilostazol on muscle ischemia-reperfusion injury in rats

PURPOSE: To evaluate effects of ischemic preconditioning and Cilostazol on muscle ischemia-reperfusion injury. METHODS: Male Wistar rats were submitted to muscle ischemic and reperfusion injury (4h of the left common iliac artery occlusion followed by 1h of reperfusion). Five experimental groups were constituted: Control group (n=4); Ischemia-Reperfusion (IR, n=5); Ischemic preconditioning group (IP, n=6); Ischemia-Reperfusion group treated with cilostazol (IRCi, n=6) and Ischemic preconditioning group treated with cilostazol (IPCi, n=6). At the end, left gracile muscle was removed and embedded in paraffin. Histopathology, neutrophil infiltration, myocyte necrosis and edema were analyzed. RESULTS: When compared with the control group, IR group showed increased neutrophil infiltration, severe necrosis and edema. There was significant difference between myocytes necrosis of IR group and IP group. There was no difference between the histopathological changes between IP, IRCi and IPCi groups. CONCLUSIONS: The model of IR caused severe muscle injury in the rat hind limb and ischemic preconditioning has a protective effect, reducing myocyte necrosis, however, treatment with cilostazol and also the association between cilostazol and preconditioning has no protective effect on the skeletal muscle subjected to ischemia and reperfusion injury. .

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy

OBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic ...

Anestésicos, precondicionamento e proteção cerebral / Anesthetics, cerebral protection and preconditioning / Anestésicos, pre-condicionamiento y protección cerebral

JUSTIFICATIVA E OBJETIVOS: Diversos estudos têm demonstrado o precondicionamento cerebral como mecanismo protetor diante de uma situação de estresse. Fatores determinantes são descritos, bem como a neuroproteção proporcionada por agentes anestésicos e não anestésicos. CONTEÚDO: Fez-se revisão baseada nos principais artigos da literatura que englobam a fisiopatologia da isquemia-reperfusão e lesão neuronal e os fatores não farmacológicos (inflamação, glicemia e temperatura) e farmacológicos relacionados com a mudança da resposta à isquemia-reperfusão, além da neuroproteção induzida pelo uso dos anestésicos. CONCLUSÕES: O cérebro tem a capacidade de se proteger contra a isquemia quando estimulado. A elucidação desse mecanismo possibilita a aplicação de substâncias indutoras do precondicionamento, como alguns anestésicos, outros fármacos e medidas não farmacológicas, como a hipotermia, com o objetivo de induzir tolerância a lesões isquêmicas.

BACKGROUND AND OBJECTIVES: Several studies demonstrate that cerebral preconditioning is a protective mechanism against a stressful situation. Preconditioning determinants are described, as well as the neuroprotection provided by anesthetic and non-anesthetics agents. CONTENT: Review based on the main articles addressing the pathophysiology of ischemia-reperfusion and neuronal injury and pharmacological and non-pharmacological factors (inflammation, glycemia, and temperature) related to the change in response to ischemia-reperfusion, in addition to neuroprotection induced by anesthetic use. CONCLUSIONS: The brain has the ability to protect itself against ischemia when stimulated. The elucidation of this mechanism enables the application of preconditioning inducing substances (some anesthetics), other drugs, and non-pharmacological measures, such as hypothermia, aimed at inducing tolerance to ischemic lesions.

JUSTIFICATIVA Y OBJETIVOS: Diversos estudios han demostrado el pre-condicionamiento cerebral como un mecanismo protector frente a una situación de estrés. Están descritos algunos factores determinantes del PC, como también la neuroprotección proporcionada por los agentes anestésicos y no anestésicos. CONTENIDO: Se hizo la revisión con base en los principales artículos de la literatura que engloban la fisiopatología de la isquemia-reperfusión y la lesión neuronal, y los factores no farmacológicos (inflamación, glucemia y temperatura), y farmacológicos relacionados con el cambio de la respuesta a la isquemia-reperfusión, además de la neuroprotección inducida por el uso de los anestésicos. CONCLUSIONES: El cerebro tiene la capacidad de protegerse contra la isquemia cuando se le estimula. La elucidación de ese mecanismo posibilita la aplicación de sustancias inductoras del precondicionamiento cerebral, como algunos anestésicos, otros fármacos y medidas no farmacológicas, como la hipotermia, con el fin de inducir la tolerancia a las lesiones isquémicas.

Effects of hyperbaric oxygen (HBO), as pre-conditioning in liver of rats submitted to periodic liver ischemia/reperfusion / Efeitos da oxigenoterapia hiperbárica como pré-condicionamento em fígados de ratos submetidos à lesão hepática de isquemia/reperfusão intermitente

PURPOSE: to assess the effect of hyperbaric oxygen (HBO) as pre-conditioning on periodic liver ischemia/reperfusion injury. METHODS: Thirty-six male Wistar rats were divided into 4 groups (SHAM, I/R , HBO-I/R and CONTROL). The surgical technique consisted of total clamping of the hepatic pedicle for 15 min followed by twice repeated reperfusion for 5 min (unclamping). HBO was applied in a collective chamber (simultaneous exposure of 4 rats) directly pressurized with oxygen at 2 ATA for 60 min. Hepatic mitochondrial function was determined using samples of the median lobe obtained after exactly 5 min of reperfusion for the analysis of mitochondrial respiration based on the determination of states 3 and 4, the respiratory control ratio and the transition of mitochondrial permeability (mitochondrial swelling).Data were analyzed by the Mann-Whitney test and the level of significance was set at p < 0.05. RESULTS: There was a statistically significant difference (p< 0.05) in state 3 between the CONTROL and I/R and HBO-I/R groups, in state 4 between the CONTROL and I/R and HBO-I/R groups; in respiratory control ratio (RCR) between the CONTROL and I/R and HBO-I/R groups and between the CONTROL and Sham groups, and in mitochondrial swelling between the CONTROL and I/R and HBO-/R groups and between the Sham and I/R and HBO-I/R groups. CONCLUSION: In this process of periodic ischemia and reperfusion, hyperbaric pre-conditioning did not improve significantly hepatic mitochondrial function.

OBJETIVO: Avaliar os efeitos da oxigenoterapia hiperbárica (HBO), como pré-condicionamento, em lesão hepática de isquemia/reperfusão intermitente. MÉTODOS: Foram avaliados 36 ratos Wistar machos, distribuídos em 4 grupos (SHAM, I/R , HBO - I/R e CONTROLE). A técnica operatória consistiu em pinçamento total do pedículo hepático durante 15min, seguido de reperfusão por 5 min (desclampeamento), por duas vezes. A aplicação de HBO foi realizada em câmara coletiva (exposição simultânea de 4 ratos) diretamente pressurizada com oxigênio a 2ATA, durante 60min. Determinou-se a função mitocondrial hepática através de amostras do lobo mediano colhidas com exatos 5min de reperfusão para análise da respiração mitocondrial, através da determinação dos estados 3 e 4, razão de controle respiratório e transição de permeabilidade mitocondrial (intumescimento osmótico - swelling mitocondrial).Os resultados foram analisados pelo teste de Mann-Whitney e foi considerado significativo todo valor de p < 0,05. RESULTADOS: Houve diferença estatistica significativa (p< 0,05) no Estado 3 nos grupos CONTROLE vs I/R e HBO - I/R, no Estado 4 nos grupos CONTROLE vs I/R e HBO - I/R; na Razão de controle respiratório(RCR) nos grupos CONTROLE vs I/R e HBO-IRe CONTROLE vs Sham e no Swelling mitocondrial nos grupos CONTROLE vs I/R e HBO - I/R, I/R vs HBO-IRe Sham vs I/R e HBO-IR. CONCLUSÃO: O pré-condicionamento hiperbárico não melhorou a função mitocondrial hepática significativamente neste processo de isquemia e reperfusão intermitente.

Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats / Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment), and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia). The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.

OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento) e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral), durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo A a função mitocondrial renal ficou desacoplada em 83,4% dos ensaios, enquanto que no grupo B isto ocorreu em apenas 38,4% dos ensaios. CONCLUSÕES: Os resultados mostram que a administração de lovastatina antes do episódio de isquemia protege a função renal. No grupo B, como a maior parte da fração mitocondrial isolada apresentou função acoplada à produção de ATP, deve-se também considerar a estabilização da membrana mitocondrial como parte da ação protetora da lovastatina na função renal durante isquemia e reperfusão.

Cyclooxygenase-2 and hypoxia-regulated proteins are modulated by basic fibroblast growth factor in acute renal failure

Acute renal failure (ARF) can be caused by injuries that induce tissue hypoxia, which in turn can trigger adaptive or inflammatory responses. We previously showed the participation of basic fibroblast growth factor (FGF-2) in renal repair. Based on this, the aim of this study was to analyze the effect of FGF-2 signaling pathway manipulation at hypoxia-induced protein levels, as well as in key proteins from the vasoactive systems of the kidney. We injected rat kidneys with FGF-2 recombinant protein (r-FGF) or FGF-2 receptor antisense oligonucleotide (FGFR2-ASO) after bilateral ischemia, and evaluated the presence of iNOS, EPO and HO-1, in representation of hypoxia-induced proteins, as well as COX-2, renin, kallikrein, and B2KR, in representation of the vasoactive systems of the kidney. A reduction in iNOS, HO-1, EPO, renin, kallikrein, B2KR, and in renal damage was observed in animals treated with r-FGF. The opposite effect was found with FGF-2 receptor down-regulation. In contrast, COX-2 protein levels were higher in kidneys treated with r-FGF and lower in those that received FGFR2-ASO, as compared to saline treated kidneys. These results suggest that the protective role of FGF-2 in the pathogenesis of ARF induced by I/R is a complex process, through which a differential regulation of metabolic pathways takes place.