Embarazo con miomatosis uterina complicado con isquemia intestinal: reporte de un caso / Pregnancy with uterine myomatosis complicated by intestinal ischemia: case report

Resumen Los miomas uterinos, también conocidos como fibromas o leiomiomas, son los tumores uterinos benignos más prevalentes. Afectan a las mujeres principalmente durante sus años reproductivos y se diagnostican hasta en un 70% de las mujeres blancas y en más del 80% de las mujeres de ascendencia africana durante su vida, con una prevalencia durante el embarazo del 2% al 10%. Pueden ser asintomáticos hasta en un 70% de las pacientes, y se estima que pueden ocurrir complicaciones en aproximadamente una de cada 10 mujeres embarazadas. Se han asociado a complicaciones y resultados adversos del embarazo, según su tamaño y ubicación en el útero, y pueden manifestarse de diferentes formas. Presentamos el caso de una mujer de 30 años, con embarazo en el tercer trimestre, quien consultó por dolor abdominal, con ecografías obstétricas durante su control prenatal que reportaban miomatosis uterina, quien presentó isquemia intestinal por un vólvulo de intestino delgado versus compresión extrínseca.

Abstract Uterine fibroids, also known as fibroids or leiomyomas, are the most prevalent benign uterine tumors, affecting women mainly during their reproductive years and are diagnosed in up to 70% of white women and more than 80% of women of African descent during their lifetime, with a prevalence during pregnancy of 2% to 10%; they may be asymptomatic in up to 70% of patients, and it is estimated that complications may occur in approximately one in 10 pregnant women. They have been associated with complications and adverse pregnancy outcomes, depending on their size and location in the uterus, they can manifest in different ways. We present the case of a 30-year-old woman, pregnant in the third trimester, who consulted for abdominal pain, with obstetric ultrasound scans during her prenatal check-up reporting uterine myomatosis, who presented intestinal ischemia due to small bowel volvulus versus extrinsic compression.

Síndrome de hiperviscosidade em paciente com mieloma múltiplo / Hyperviscosity syndrome in multiple myeloma patients

O mieloma múltiplo é uma neoplasia progressiva e incurável de células B, caracterizado pela proliferação desregulada e clonal de plasmócitos na medula óssea. A síndrome de hiperviscosidade é uma das complicações relacionadas às gamopatias monoclonais, sendo considerada emergência oncológica. O objetivo deste estudo foi descrever o quadro clínico de um paciente diagnosticado com mieloma múltiplo que apresentou síndrome de hiperviscosidade, avaliando a prevalência de sinais e sintomas, bem como características fisiopatológicas dessa entidade clínica. Foi revisado o prontuário de um paciente internado na enfermaria da Clínica Médica do Hospital Regional do Cariri (CE) no período de junho a julho de 2018. Além disso, foi realizada revisão de literatura em base de dados (PubMed®) direcionada ao tema proposto. O diagnóstico de mieloma múltiplo foi comprovado por mielograma, sendo prontamente iniciada a corticoterapia e avaliada a resposta clínica após essa terapêutica. Apesar de incomum e menos frequentemente relacionada ao mieloma múltiplo, a síndrome de hiperviscosidade está relacionada a uma grande taxa de mortalidade quando apresenta diagnóstico tardio. A terapia de primeira linha indicada para a síndrome de hiperviscosidade foi a plasmaferese, no entanto, as condições clínicas (instabilidade hemodinâmica) impossibilitaram sua realização. O desfecho deste caso foi o óbito do paciente. Concluiu-se que o diagnóstico precoce e a intervenção terapêutica estão diretamente relacionados à ocorrência de menor incidência de complicações relacionadas ao mieloma múltiplo e à síndrome de hiperviscosidade.

Multiple myeloma is a progressive and incurable B-cell neoplasm characterized by unregulated and clonal proliferation of plasmocytes in the bone marrow. Hyperviscosity syndrome is one of the complications related to monoclonal gammopathies and is considered an oncological emergency. The aim of this study was to describe the clinical condition of a patient diagnosed with multiple myeloma who presented hyperviscosity syndrome, evaluating the prevalence of symptoms and signs, as well as the pathophysiological characteristics of this clinical entity. The medical records of a patient admitted to the Internal Medicine ward of the Hospital Regional do Cariri (CE) from June to July of 2018 were reviewed. In addition, we conducted a literature review in a database (PubMed®) directed to the theme proposed. The diagnosis of multiple myeloma was confirmed by myelogram, and corticosteroid therapy was promptly initiated and the clinical response was evaluated after this therapy. Although uncommon and less frequently related to multiple myeoloma, hyperviscosity syndrome is related to a high mortality rate when diagnosed late. The first line therapy indicated to hyperviscosity syndrome was plasmapheresis; however, the clinical conditions (hemodynamic instability) precluded its performance. The outcome of this case was the patient's death. Thus, it was concluded that early diagnosis and therapeutic intervention are directly related to the occurrence of lower incidence of complications related to multiple myeloma and hyperviscosity syndrome.

Effect of hyperbaric oxygenation on the expression of glutathione peroxidase 4 and lactoperoxidase genes in the lung of isogenic mice after ischemia/reperfusion injury in the small bowel

Abstract Purpose: To evaluate the effect of hyperbaric oxygenation (HBO) on the expression of the genes antioxidant glutathione peroxidase 4 (Gpx4) and lactoperoxidase (Lpo) in the lung of mice subjected to intestinal ischemia and reperfusion (IIR). Methods: Control group (CG) in which were subjected to anesthesia, laparotomy and observation for 120 minutes; an ischemia and reperfusion group (IRG) subjected to anesthesia, laparotomy, small bowel ischemia for 60 minutes and reperfusion for 60 minutes; and three groups treated with HBO during ischemia (HBOG + I), during reperfusion (HBOG + R) and during ischemia and reperfusion (HBOG + IR). Studied 84 genes of oxidative stress by the method (RT-qPCR). Genes with expression levels three times below or above the threshold cycle were considered significantly hypoexpressed or hyperexpressed, respectively (Student's t-test p<0.05). Results: Gpx4 and Lpo were hiperexpressed on IRG, showing a correlation with these genes with lung oxidative stress. Treated with HBO, there was a significant reduction on genic expression on HBOG+I. Conclusion: Hyperbaric oxygenation showed to be associated with decreased expression of these antioxidant genes, suggesting a beneficial effect on the mechanism of pulmonary oxidative stress whenever applied during the ischemia.

Hyperbaric oxygenation and the genic expression related to oxidative stress in the heart of mice during intestinal ischemia and reperfusion

Abstract Purpose: To investigate the effects of hyperbaric oxygenation (HBO) on intestinal ischemia and reperfusion (IR) injury, we evaluated the expression of 84 genes related to oxidative stress and the antioxidant response in mouse hearts. Methods: Four groups were subjected to 60 minutes of intestinal ischemia followed by 60 minutes of reperfusion: IRG, ischemia and reperfusion group without HBO; HBO-IG, which received HBO during ischemia; HBO-RG, which received HBO during reperfusion; and HBO-IRG, which received HBO during ischemia and reperfusion. The control group (CG) underwent anesthesia and laparotomy and was observed for 120 minutes. The (RT-qPCR) method was applied. Genes with expression levels three times below or above the threshold cycle were considered significantly hypoexpressed or hyperexpressed, respectively (Student's t-test p<0.05). Results: Eight genes (9.52%) were hyperexpressed in the IRG. When the HBO groups were compared to the IRG, we found a decrease in the expression of eight genes in the HBO-IG, five genes in the HBO-RG, and seven genes in the HBO-IRG. Conclusion: The reduction in the expression of genes related to oxidative stress and antioxidant defense following HBO in mouse hearts resulting from intestinal IR injury was more favorable during the ischemic period than during the reperfusion period.

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

Abstract Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.

The expression of endothelial and inducible nitric oxide synthase and apoptosis in intestinal ischemia and reperfusion injury under the action of ischemic preconditioning and pentoxifylline

Abstract Purpose: To investigate the expression of nitric oxide synthase (NOS) and apoptosis associated with ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal ischemia (I) and reperfusion (R) injury. Methods: Thirty male rats were assigned to 5 groups: (CG), no clamping of the superior mesenteric artery (90 minutes); (IR-SS) saline + ischemia (30 minutes) + reperfusion (60 minutes); (IR-PTX) PTX + ischemia (30 minutes) + reperfusion (60 minutes); (IPC-IR-SS) 5 minutes of ischemia + 5 minutes of reperfusion (IPC) + saline + I(30 minutes)+R(60 minutes); and (IPC-IR-PTX) IPC + PTX + I(30 minutes)+ R(60 minutes). Results: The application of IPC and PTX showed a significantly lower immunohistochemistry reaction for active caspase-3 (P<0.05) compared to IR+SS. The number of cells immunoreactive to BCL-2 was higher in the IR-PTX group (P>0.05). The NOS-2 expression (qRTPCR) in the IR-PTX group (P<0.05) was higher than the values for the IPC+IR-SS and IPC-IR-PTX groups. The NOS-3 expression was significantly upper in the IPC-IR-PTX group than in the CG (P<0.05), the IR-SS (P<0.05) and the IR-PTX (P<0.05) groups. Conclusions: The BCL-2 and active caspase-3 showed beneficial effects on PTX and IPC. The expression of NOS-2 and NOS-3 in the IPC and IPC-PTX groups showed no synergistic effect.

The role of ischemic preconditioning and pentoxifylline in intestinal ischemia/reperfusion injury of rats

Abstract Purpose: To investigate the role of ischemic preconditioning (IPC) and pentoxifylline (PTX) in intestinal mucosa ischemia/reperfusion injury (IR). Methods: Thirty rats were assigned to 5 groups (N=6): (CG): no clamping of the superior mesenteric artery (90 min.); (IR-SS): saline + ischemia (30 min.) + reperfusion (60 min.); (IR-PTX): PTX + ischemia (30min.) + reperfusion (60 min.); (IPC-IR-SS): 5 min. of ischemia + 5 minutes of reperfusion (IPC) + saline + ischemia (30 min.) + reperfusion (60 min.); (IPC-IR-PTX ): 5 min. of ischemia + 5 min. of reperfusion (IPC) + PTX + 30 min. of I + 60 minutes of R. Results: The IR-PTX, IPC-IR-SS and IPC-IR-PTX groups had significantly lower scores of mucosa damage than the IR-SS group. IR-PTX group showed higher scores than the IPC-IR-PTX group, in accordance with the hypothesis of a favorable effect of IPC alone or in association with PTX. Additionally, IPC-IR-SS had a higher damage score than the IPC-IR-PTX. The villi height and crypt depth were similar in all groups. The villi height in the IR-SS was significantly lower. Conclusion: Ischemic preconditioning or pentoxifylline alone protect the intestinal mucosa from ischemia/reperfusion injury. However, they do not have a synergistic effect when applied together.

Origem e principais ramificações das artérias mesentéricas cranial e caudal em avestruz (Struthio camelus Linnaeus, 1758) / Origin and main ramifications of the cranial and caudal mesenteric arteries in ostrich (Struthio camelus Linnaeus, 1758)

As artérias mesentéricas das aves são importantes para a irrigação do aparelho digestório e encontram-se associadas ao ganho de peso e conversão alimentar. Objetivou-se descrever as origens, esqueletopias, medidas e principais ramificações das artérias mesentéricas cranial e caudal em avestruzes. Foram utilizados 41 cadáveres de filhotes de avestruzes, 23 machos e 18 fêmeas, obtidos de um criadouro após morte natural. Os cadáveres foram fixados com formaldeído a 10% e tiveram o sistema vascular preenchido com Petrolatex® S-65 colorido. As artérias mesentéricas, cranial e caudal e seus ramos proximais foram dissecados "in situ" e medidas com paquímetro digital. A artéria mesentérica cranial teve comprimento médio de 3,68 ± 1,04 cm e surgiu da aorta descendente ao nível da oitava vértebra torácica na maioria dos casos. Ramificou-se em artérias jejunal e ileocecal. A artéria jejunal ofereceu média de 14,04 ±2,08 ramos ao jejuno e a artéria ileocecal originou um ramo retal e outro que se bifurcou para derivar ramos para íleo, ceco e reto. Em um espécime macho a artéria ileocecal foi ramo da artéria celíaca. A artéria mesentérica caudal originou-se na porção terminal da aorta descendente predominantemente ao nível das 4ª e 6ª vértebras sacro-caudais. Perto da extremidade caudal do rim emitiu os ramos cranial e caudal. O primeiro irrigou o reto e anastomosou-se com ramo retal da artéria mesentérica cranial; o segundo irrigou a porção final do reto, cloaca e bolsa cloacal. Não houve diferença significativa (p<0,05) entre as medidas, esqueletopia e número de ramificações das artérias entre os sexos.(AU)

The mesenteric arteries of birds are important for the irrigation of the digestive tract and are associated with weight gain and food conversion. This study aimed to describe the origins, skeletopy, measures and main branches of cranial and caudal mesenteric arteries in ostriches. Forty-one cadavers of ostrich chicks, 23 males and 18 females, obtained from a farmer after natural death. The cadavers were fixed with 10% formaldehyde solution and their vascular system was filled with colored Petrolatex® S-65. The cranial and caudal mesenteric arteries and its proximal branches were dissected in situ and measured with a digital caliper. The mesenteric artery had an average length of 3.68cm±1.04 and emerged from the descending aorta at the level of the eighth thoracic vertebra in most cases; it branched into jejunal and ileocecal arteries. The jejunal artery sent a mean of 14 (14.04±2.08) branches to the jejunum. The ileocecal artery sent a rectal branch and another branch that irrigated ileum, cecum and rectum. In a male specimen the ileocecal artery was originated from the celiac artery. The caudal mesenteric artery emerged in the terminal portion of the descending aorta predominantly at the level of the 4th and 6th sacrocaudal vertebrae. Near the caudal end of the kidney it issued the cranial and caudal branches. The first irrigated the rectum and anastomosed with the rectal branch of the cranial mesenteric artery; the second irrigated the final part of the rectum, cloaca and cloacal bursa. There was no significant difference (p<0.05) between measurements, skeletopy and number of branches of the arteries between genders.(AU)

Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats

ABSTRACT PURPOSE: To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injury METHODS: Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels. RESULTS: Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups. CONCLUSION: The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury.

Effects of Potentilla Fulgens as Prophylactic Agent in Intestinal Ischemia Reperfusion Injury / Efectos de Potentilla fulgens como Agente Profiláctico en la Lesión por Isquemia-Reperfusión Intestinal

The purpose of this study, ischemia reperfusion injury in rats, Potentilla fulgens is to investigate the protective effects. Wistar albino rats (n= 30) weighing 180-220 g were used in the experiment. Group 1 animals underwent sham laparotomy without ischemia-reperfusion injury. Group 2 animals underwent laparotomy and occlusion of superior mesenteric arteries for 30 min followed by 20 min of reperfusion without pretreatment. The Potentilla fulgens group received 400 mg/kg/day Potentilla fulgens intraperitoneally 5 days before Ischemia-reperfusion injury. There was a significant difference between the group with ischemia-reperfusion group Potentilla fulgens (p<0.0001). In statistical analysis of the MDA level, data were obtained after a respective measurement in all groups. Potentilla fulgens group with ischemia-reperfusion group was a significant decrease in MDA (p<0.001). In the period after ischemia-reperfusion, marked PCNA immunoreactivities were observed in the nuclei of crypt and villus cell. In ischemia reperfusion group, the number of PCNA immunoreactivity is quite advanced and they extended throughout the middle part of the intestine folds. The number of TUNEL-positive nuclei were also developed. In ischemia-reperfusion plus P. fulgens group, the intestinal epithelium with only a few PCNA immunoreactive nuclei. TUNEL positive nuclei were noted in the gut lumen and mucosal close differentiated goblet cells. We showed that Potentilla fulgens extract significantly prevented mucosal lesions caused by intestinal ischemia-reperfusion.

El objetivo fue investigar los efectos protectores de Potentilla fulgens sobre la lesión por isquemia-reperfusión en ratas albinas Wistar (n= 30) con un peso de 180 g. En el grupo 1, los animales fueron sometidos a laparotomía simulada sin lesión por isquemia-reperfusión. En el Grupo 2, los animales fueron sometidos a laparotomía y oclusión de las arteria mesentérica superior durante 30 min seguido de 20 min de reperfusión sin pretratamiento. El grupo Potentilla fulgens recibió 400 mg/kg/día de P. fulgens por vía intraperitoneal 5 días antes de la lesión por isquemia-reperfusión. Hubo diferencias significativas entre el grupo de grupo con isquemia-reperfusión y el tratado con Potentilla fulgens (p<0,0001). En el análisis estadístico del nivel de malondialdehído (MDA), los datos se obtuvieron después de una medición respectiva en todos los grupos. Los grupos Potentilla fulgens y con isquemia-reperfusión tuvieron una disminución significativade MDA (p<0,0001). En el periodo después de la isquemia-reperfusión, se observó inmunorreactividad del marcador PCNA en los núcleos de las células de las criptas y vellosidades. En el grupo de isquemia-reperfusión, la inmunoreactividad a PCNA fue bastante avanzada y se extendió a lo largo de la parte media de los plieges intestinales. También aumentó el número de núcleos positivos a TUNEL. En el grupo isquemia-reperfusión tratado con P. fulgens, el epitelio intestinal mostró pocos núcleos inmunorreactivos a PCNA; núcleos positivos a TUNEL se observaron en el lumen intestinal y la mucosa, cerca de las células caliciformes diferenciadas. Demostramos que el extracto de P. fulgens disminuye significativamente lesiones de la mucosa intestinal causadas por la isquemia-reperfusión.

Evaluation of the effects of ischemic preconditioning on the hematological parameters of rats subjected to intestinal ischemia and reperfusion

OBJECTIVES: Intestinal ischemia/reperfusion often leads to acute lung injury and multiple organ failure. Ischemic preconditioning is protective in nature and reduces tissue injuries in animal and human models. Although hematimetric parameters are widely used as diagnostic tools, there is no report of the influence of intestinal ischemia/reperfusion and ischemic preconditioning on such parameters. We evaluated the hematological changes during ischemia/reperfusion and preconditioning in rats. METHODS: Forty healthy rats were divided into four groups: control, laparotomy, intestinal ischemia/reperfusion and ischemic preconditioning. The intestinal ischemia/reperfusion group received 45 min of superior mesenteric artery occlusion, while the ischemic preconditioning group received 10 min of short ischemia and reperfusion before 45 min of prolonged occlusion. A cell counter was used to analyze blood obtained from rats before and after the surgical procedures and the hematological results were compared among the groups. RESULTS: The results showed significant differences in hematimetric parameters among the groups. The parameters that showed significant differences included lymphocyte, white blood cells and granulocyte counts; hematocrit; mean corpuscular hemoglobin concentration; red cell deviation width; platelet count; mean platelet volume; plateletcrit and platelet distribution width. CONCLUSION: The most remarkable parameters were those related to leukocytes and platelets. Some of the data, including the lymphocyte and granulocytes counts, suggest that ischemic preconditioning attenuates the effect of intestinal ischemia/reperfusion on circulating blood cells. Our work contributes to a better understanding of the hematological responses after intestinal ischemia/reperfusion and IPC, and the present findings may also be used as predictive values. .

Isquemia intestinal, reconocimiento y manejo / Intestinal ischemia, diagnosis and treatment

Intestinal ischemia remains a high risk mortality disease. Early detection has a huge impact in survival. The development of new biochemical markers will be useful in ischemia screening. Computed tomography (CT) scan and AngioTC, has a great value to assess viability of small bowel areas. Basic treatment and even surgery have the best results in early diagnosis setting.

La isquemia intestinal continúa siendo una patología de alto riesgo de mortalidad. El reconocimiento clínico precoz tiene impacto en la sobrevida. Se están desarrollando nuevos marcadores bioquímicos para optimizar la pesquisa de isquemia. En estos casos, la tomografía computada (TC) multicorte y angioTC, son de gran utilidad para establecer la viabilidad de un segmento y la probabilidad de resección. En tratamiento general y quirúrgico si corresponde, tiene mejores resultados en escenarios de diagnóstico precoz.

Very short cycles of postconditioning have no protective effect against reperfusion injury. Experimental study in rats / Ciclos muito curtos de pós-condicionamento não protegem contra lesão de reperfusão. Estudo experimental em ratos

Introduction: Ischemic postconditioning has been recognized as effective in the prevention of reperfusion injury in situations of ischemia and reperfusion in various organs and tissues. However, it remains unclear what would be the best way to accomplish it, since studies show great variation in the method of their application. Objective: To assess the protective effect of ischemic postconditioning on ischemia and reperfusion in rats undergoing five alternating cycles of reperfusion and ischemia of 30 seconds each one. Methods: We studied 25 Wistar rats distributed in three groups: group A (10 rats), which underwent mesenteric ischemia (30 minutes) and reperfusion (60 minutes); Group B (10 rats), undergoing ischemia (30 minutes) and reperfusion (60 minutes), intercalated by postconditioning (5 alternating cycles of reperfusion and ischemia of 30 seconds each one); and group C - SHAM (5 rats), undergoing only laparotomy and manipulation of mesenteric artery. All animals underwent resection of an ileum segment for histological analysis. Results: The mean lesions degree according to Chiu et al. were: group A, 2.77, group B, 2.67 and group C, 0.12. There was no difference between groups A and B (P>0.05). Conclusion: Ischemic postconditioning was not able to minimize or prevent the intestinal tissue injury in rats undergoing ischemia and reperfusion process when used five cycles lasting 30 seconds each one. .

Introdução: O pós-condicionamento isquêmico tem sido reconhecido como eficaz na prevenção das lesões de reperfusão em situações de isquemia e reperfusão em vários órgãos e tecidos. Entretanto, não está ainda claro qual seria a melhor maneira de realizá-lo, já que as publicações mostram grande variação de método no seu emprego. Objetivo: Avaliar o efeito protetor do pós-condicionamento isquêmico na isquemia e reperfusão intestinal em ratos, através de cinco ciclos alternados de 30 segundos de isquemia e 30 segundos de reperfusão. Métodos: Foram estudados 25 ratos Wistar, distribuídos em três grupos: grupo A (10 ratos), em que se realizou isquemia (30 minutos) e reperfusão (60 minutos) mesentérica; grupo B (10 ratos), isquemia e reperfusão, seguidos de pós-condicionamento isquêmico com 5 ciclos alternados de reperfusão e reoclusão, de 30 segundos cada; e grupo C (5 ratos), controle (SHAM). Ao final, ressecou-se um segmento do intestino delgado para análise histológica. Avaliaram-se os resultados pela classificação de Chiu et al. e procedeu-se ao tratamento estatístico. Resultados: As médias dos graus de lesão tecidual segundo a classificação de Chiu et al. foram: no grupo A, 2,77; no grupo B, 2,67; e no grupo C, 0,12. A diferença entre o resultado do grupo A com o resultado do grupo B não teve significância estatística (P>0,05). Conclusão: O pós-condicionamento isquêmico não foi capaz de minimizar ou prevenir a lesão tecidual intestinal de ratos submetidos ao processo de isquemia e reperfusão mesentérica quando utilizados cinco ciclos com duração de 30 segundos cada. .

Pentoxifylline associated to hypertonic saline solution attenuates inflammatory process and apoptosis after intestinal ischemia/reperfusion in rats

PURPOSE: To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline. METHODS: It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4ml/kg-IV); PTX group (Pentoxifylline, 30mg/kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3. RESULTS: The values of sO2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR). CONCLUSION: The combined use of pentoxifylline and hypertonic saline offers best results on inflammatory and apoptotic inhibitory aspects after intestinal ischemia/reperfusion. .

O impacto das soluções hipertônica e salina fisiológica na reperfusão do trato gastrintestinal pós-isquemia em ratos / The impact of hypertonic and normal saline in gut reperfusion after ischemia in rats

Objetivo: Investigar o papel de duas diferentes soluções salinas nos mecanismos de lesão após isquemia intestinal: estresse oxidativo e respostas inflamatórias. Métodos: Ratos Wistar foram submetidos a oclusão transitória da artéria mesentérica superior e estudados durante as 6 horas seguintes à reperfusão. Após randomização, os animais foram divididos em quatro grupos: Falso; Solução Hipertônica, os quais receberam infusão de solução salina hipertônica a 7,5% (4mL/kg de peso corpóreo); Solução Fisiológica, os quais receberam infusão de solução salina a 0,9% (33mL/kg); e Sem Tratamento. A infusão foi realizada imediatamente antes da reperfusão. Foram realizadas dosagens sequenciais de interleucina 6 e interleucina 10 no plasma. Foram coletadas amostras de tecidos (pulmão, fígado e intestino) para medir malondialdeído, mieloperoxidase e interleucina. Resultados: Em comparação ao Grupo Sem Tratamento, os animais que receberam volume (Grupos Solução Hipertônica e Solução Fisiológica) mostraram níveis tissulares mais baixos de malondialdeído, mieloperoxidase, interleucina 6 e interleucina 10. As concentrações plasmáticas de interleucina 6 e interleucina 10 foram mais altas nos animais tratados com solução hipertônica do que nos tratados com solução fisiológica e nos sem tratamento. Conclusão: Neste modelo de isquemia intestinal transitória, a manutenção adequada de volume intravascular diminuiu o estresse oxidativo e a síntese de marcadores de inflamação. Tanto a solução hipertônica quanto a fisiológica atenuaram os efeitos deletérios observados após isquemia intestinal. .

Objective: We investigated the effect of two different saline solutions on the mechanisms of injury after intestinal ischemia: oxidative stress and inflammatory responses. Methods: Wistar rats underwent transient superior mesenteric artery occlusion and were studied for 6 hours after reperfusion. After randomization, the animals were divided into four groups: Sham; Hypertonic Saline, in which they received infusion of 4mL/kg body weight of 7.5% hypertonic saline; Saline, in which they received infusion of 33mL/kg body weight of 0.9% saline; and Non Treatment. The infusion was performed immediately prior to the reperfusion. The plasma concentrations of interleukin 6 and interleukin 10 were measured. Tissue samples (lung, liver, and intestine) were collected for malondialdehyde, myeloperoxidase, and interleukin measurements. Results: The animals that received infusions (Hypertonic Saline and Saline) showed lower levels of tissue malondialdehyde, myeloperoxidase, interleukin 6, and interleukin 10 compared with the Non Treatment group. The plasma concentrations of interleukin 6 and interleukin 10 were higher in the animals treated with 7.5% hypertonic saline compared with Saline and Non Treatment groups. Conclusion: In this model of transient intestinal ischemia, the adequate maintenance of intravascular volume decreased oxidative stress and the synthesis of inflammatory markers. Both 7.5% Hypertonic Saline and Saline attenuated the deleterious effects observed after intestinal ischemia. .

Heparin modulates the expression of genes encoding pro and anti-apoptotic proteins in endothelial cells exposed to intestinal ischemia and reperfusion in rats

PURPOSE: To investigate if expression of genes encoding pro and anti-apoptotic proteins in the rat enteric endothelial cells stimulated by intestinal ischemia followed by reperfusion (IR) can be modified by treatment with heparin (HP). METHODS: Eighteen adult Wistar rats were divided in three groups: sham group submitted to laparotomy only (SG), ischemia followed by reperfusion group (IRG); ischemia followed by reperfusion plus pretreatment with HP 100 mg.kg-1 (IRG+HP). Ischemia was performed by clamping of the superior mesenteric artery. After 60 min of ischemia, metal clamps were removed for reperfusion for 120 min. Gene expression of encoding pro (Casp1, Casp6, Casp3, Cflar, Fas and Pgl) and anti-apoptotic (Bcl2, Bcl2l1 and Naip2) proteins in rat enteric endothelial cells was evaluated by PCR microarray method. RESULTS: Compared to rat endothelial cells of SG, the expression of pro-apoptotic genes was up-regulated in IRG while anti-apoptotic genes were down-regulated. In contrast, the expression of anti-apoptotic genes in IRG+HP was up-regulated while pro-apoptotic genes was down-regulated compared to SG. CONCLUSION: The attenuation by heparin of intestinal ischemia-reperfusion previously demonstrated in rodents could be related with ability of this drug to stimulate and reduce gene expression of encoding anti and pro-apoptotic proteins, respectively. .

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.

Heart injury following intestinal ischemia reperfusion in rats is attenuated by association of ischemic preconditioning and adenosine

PURPOSE: To investigate the effect of ischemic preconditioning (IPC) and adenosine as strategies to protect cardiac injury caused by intestinal IR in rats, based on increasing in adenosine bioavailability and improvement of cell energy state by IPC. METHODS: Male Wistar rats were submitted to 60 minutes of intestinal ischemia and 120 minutes of reperfusion. Intravenous injections of saline or Adenosine (AD) was administered five minutes before ischemia, five minutes before reperfusion and after 55 minutes reperfusion. Cardiac samples were obtained, fixed in formalin solution, embedded in paraffin, and sections of 5 μm were stained by hematoxylin-eosin. Histological analysis of myocardium was performed according occurrence of necrosis signs: piknosis, band contraction, eosinophilic cytoplasm, karyorrhexis and vacuolization (score - zero to 5). RESULTS: The groups submitted to ischemia alone (I=4.0), and reperfusion (IR=4.5) showed highest level of lesion compared to the others (I+IPC=3.3, IR+IPC=3.6, I+AD=3.0, IR+AD=3.8). The most interesting result was association of IPC and AD in IR model (IR+IPC+AD=1.2, p=0.002), showing preservation of the heart tissue, with fibers showing typical cross-striations and nuclei characteristics. Rare and small areas of tissue necrosis was observed and suggestion of capillaries congestion. CONCLUSION: Intestinal ischemia reperfusion promotes cardiac tissue injury. Ischemic preconditioning in association with adenosine is an efficient strategy to protect the heart against ischemia and reperfusion injury. .

Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis ...