Isquemia intestinal, una manifestación inusual de la embolia paradójica. Un reporte de caso / Intestinal ischaemia as a rare manifestation of a paradoxical embolism. A case report

Introducción. La embolia paradójica es un evento trombótico originado en la circulación venosa, que se manifiesta como embolismo arterial por medio de un defecto anatómico a nivel cardíaco o pulmonar. Se asocia principalmente a eventos cerebrovasculares, aunque se han encontrado casos de infarto agudo de miocardio, infarto renal y otros eventos isquémicos. Caso clínico. Paciente de 47 años, quien consultó por cuadro de dolor abdominal, que requirió manejo quirúrgico de urgencia, donde identificaron isquemia intestinal importante. Los estudios adicionales hallaron déficit de proteína S y persistencia de foramen oval permeable. Resultados. La presencia de trombosis arterial se conoce como trombosis de sitios inusuales y requiere de estudios para descartar trombofilias asociadas u otros estados protrombóticos. El déficit de proteína S es una trombofilia infrecuente, la cual se asocia en la vida adulta a eventos trombóticos de origen venoso. En presencia de defectos anatómicos, como un foramen oval permeable, puede progresar a embolia arterial, configurando un cuadro de embolismo paradójico. La estratificación de estos pacientes requiere imágenes que demuestran el defecto mencionado, así como el posible origen de los émbolos. El manejo se basa en anticoagulación plena, manejo de soporte, resolver las manifestaciones trombóticas existentes y un cierre temprano del defecto anatómico. Conclusiones. El embolismo paradójico debe sospecharse en caso de trombosis de sitios inusuales. Requiere de un estudio exhaustivo con imágenes y su manejo debe basarse en anticoagulación y cierre del defecto.

Introduction. Paradoxical embolism is a thrombotic event originating in the venous circulation, which manifests as arterial embolism through an anatomical cardiac or pulmonary defect. It is mainly associated with stroke, also presenting as acute myocardial infarction, renal infarction, and other ischemic events. Clinical case. A 47-year-old patient was admitted due to abdominal pain, which required emergency surgical management, finding significant intestinal ischemia. Additional studies found protein S deficiency and evidence of a patent foramen ovale. Discussion. Arterial thrombosis is known as unusual thrombosis; this situation requires to rule out associated thrombophilia or other prothrombotic diseases. Protein S deficiency is a rare thrombophilia, which in adults causes venous thrombosis. In the presence of anatomical defects, such as a patent foramen ovale, it can progress to arterial embolism, presenting a picture of paradoxical embolism. The study work of these patients requires imaging that demonstrates the aforementioned defect, as well as the possible origin of the emboli. Management is based on full anticoagulation, treatment of existing thrombotic manifestations, and management of the anatomical defect. Conclusions. Paradoxical embolism should be suspected in case of unusual thrombosis. It requires exhaustive studies based on imaging, and management should consist of anticoagulation and closure of the defect.

Puerarin protects the fatty liver from ischemia-reperfusion injury by regulating the PI3K/AKT signaling pathway

Abstract The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.

Arterialização venosa superficial com veia safena magna in situ: a experiência de um único centro / Superficial venous arterialization with the great saphenous vein in situ: a single-center experience

Resumo Contexto A arterialização do arco venoso dorsal do pé é uma técnica indicada em casos de isquemia crítica de membros inferiores sem leito distal adequado que possibilite tratamento convencional, como revascularização, angioplastia ou tratamento clínico. Objetivos O propósito do trabalho foi apresentar o resultado da arterialização do arco venoso do pé em 16 pacientes submetidos a essa técnica. Métodos Tratou-se de um estudo analítico descritivo retrospectivo transversal, baseado na revisão de prontuários de 16 pacientes submetidos à arterialização do arco venoso dorsal do pé para salvamento de membro, entre janeiro de 2016 a janeiro de 2021. Resultados Dos 16 pacientes submetidos à arterialização do arco venoso do pé, 25% (4) evoluíram para amputação maior durante a mesma internação, e 6,25% (1) pacientes evoluíram para amputação maior após 6 meses. Os demais pacientes (68,75%, 11) tiveram seus membros preservados, sendo que 10 foram submetidos a amputações menores (pododáctilos e antepé), e 1 paciente não necessitou de procedimento adicional. Conclusões A técnica de arterialização do arco venoso dorsal do pé deve ser considerada em casos selecionados. Trata-se de uma alternativa válida para a preservação do membro na impossibilidade de tratamento convencional.

Abstract Background Arterialization of the dorsal venous arch of the foot is a technique indicated in cases of critical lower limb ischemia that do not have a distal bed that is adequate to enable conventional treatment such as revascularization, angioplasty, or clinical treatment. Objectives The purpose of this study is to present the result of arterialization of the venous arch of the foot in 16 patients who underwent treatment with this technique. Methods This is a cross-sectional retrospective descriptive analytical study based on a review of the medical records of 16 patients who underwent arterialization of the dorsal venous arch of the foot for limb salvage from January 2016 to January 2021. Results Four (25%) of the 16 patients who underwent arterialization of the venous arch of the foot underwent a major amputation during the same hospital stay and one patient (6.25%) had a major amputation within 6 months. The other 11 patients (68.75%) had their limbs preserved, with 10 undergoing minor amputations (toes and forefoot) and one patient having no additional procedures. Conclusions We conclude that the technique of arterialization of the dorsal venous arch of the foot should be considered in selected cases. It is a valid alternative for limb salvage when conventional treatment is impossible.

Isquemia mesentérica aguda: un desafío de la medicina. Reporte de un caso

La isquemia intestinal aguda es una emergencia vascular provocada por fenómenos oclusivos y no oclusivos de la circulación mesentérica arterial y venosa, de difícil diagnóstico y pronóstico ominoso. Su incidencia va en aumento paulatino con el decurso de los años, asociada fundamentalmente al envejecimiento de la población. La tasa de mortalidad es elevada a pesar de los avances en el campo de la imagenología. Suele diagnosticarse de forma tardía, cuando está establecido el daño isquémico intestinal de carácter irreversible. El elemento imprescindible e indispensable lo constituye el tiempo que trascurre hasta la cirugía, por lo que su diagnóstico sigue siendo un reto clínico. El tratamiento exige medidas médicas intensivas, al igual que cirugía de revascularización y resección del intestino necrosado. Por desdicha, el examen físico y los hallazgos de laboratorio no son sensibles ni específicos para su diagnóstico. Teniendo en cuenta estos elementos, se presenta el caso de una paciente de 38 años con clínica difusa de vómitos, diarrea y dolor abdominal progresivo, que requirió intervención quirúrgica de urgencia con diagnóstico transoperatorio de isquemia mesentérica aguda. Durante su estancia hospitalaria se relaparotomizó en dos ocasiones, mantuvo soporte ventilatorio e inotrópico por fallo multiorgánico en la Unidad de Cuidados Intensivos, mostrando una adecuada evolución posquirúrgica. El objetivo de esta presentación es enfatizar en la clínica como elemento fundamental para abordar de forma correcta esta entidad en un medio hospitalario de limitados recursos diagnósticos imagenológicos, al abordar conceptos teóricos recientes y facilitar una adecuada actuación en la toma de decisiones.

Acute intestinal ischemia is a vascular emergency caused by occlusive and non-occlusive phenomena of the mesenteric arterial and venous circulation of difficult diagnosis and ominous prognosis. Its incidence is gradually increasing over the years, mainly associated with the ageing of the population. The mortality rate is high despite advances in the field of imaging. It is usually diagnosed late, when irreversible ischemic intestinal damage is established. The essential and indispensable element is the time that elapses until surgery, so its diagnosis continues to be a clinical challenge. Treatment requires intensive medical measures, as well as revascularization surgery and resection of the necrotic intestine. Unfortunately, physical examination and laboratory findings are neither sensitive nor specific for its diagnosis. Taking these elements into account, the authors present the case of a 38-year-old female patient with diffuse symptoms of vomiting, diarrhea and progressive abdominal pain that required emergency surgery with intraoperative diagnosis of acute mesenteric ischemia. During her hospital stay, she underwent re-laparotomy twice, maintained ventilatory and inotropic support due to multi-organ failure in the Intensive Care Unit, showing an adequate post-surgical evolution. The objective of this presentation is to emphasize in the clinic as a fundamental element to correctly address this entity in a hospital environment with limited imaging diagnostic resources by addressing recent theoretical concepts and facilitating adequate action in decision-making.

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

Purpose: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Methods: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. Results: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). Conclusions: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

Garlic Extract Reverses Ischemic Heart Disease in Female Rats Exposed to Combined Oral Contraceptive Pills

Abstract Background Garlic is an herbal medicinal plant with several pharmacological properties used for the management of various ailments. However, its potential in the reversal of ischemic heart disease induced by combined oral contraceptive pills is not well reported. Objective This study investigated the cardioprotective potential of aqueous garlic extract against cardiotoxicity induced by oral contraceptive pills. Methods Forty-six rats were used for this study. Six were used to determine the lethal dose (LD50), and 40 rats were divided randomly into 5 groups of 8 rats each. Group A received feed and distilled water. Group B received 0.6 mg/kg of oral contraceptive pills. Group C received 500 mg/kg of garlic extract. Group D received 0.6 mg/kg of oral contraceptive pills + 500 mg/kg garlic extract. Group E received 0.6 mg/kg of oral contraceptive pills + 700 mg/kg garlic extract. The animals were sacrificed, and blood and tissue samples were collected for biochemical and histological analysis. Statistical analysis was done using SPSS, and p values < 0.05 were considered significant. Results The acute toxicity dose of combined oral contraceptive pills was 1.5 mg/kg for albino rats. Combined oral contraceptive pills induced ischemic necrosis as revealed by the photomicrographs, in addition to elevation of serum cardiac troponin-1, lactate dehydrogenase, creatine kinase, and malondialdehyde levels. Treatment with garlic extract demonstrated significant reduction in cardiac troponin-1 (p = 0.000), lactate dehydrogenase (p = 0.002), creatine kinase (p = 0.001), and malondialdehyde (p = 0.001) levels, as well as restoration of the cardiac cytoarchitecture changes caused by the combined oral contraceptive pills. Conclusion This study has demonstrated that aqueous garlic juice can reverse ischemic heart disease, lessen cytoarchitectural alterations of the heart caused by combined oral contraceptive pills, and thus ameliorate cardiac dysfunction.

Isquemia de mão de pacientes em terapia renal substitutiva: avaliação por termografia / Isquemia de mano de pacientes en terapia de reemplazo renal: evaluación por termografía / Hand ischemia in patients undergoing renal replacement therapy: assessment by thermography

Resumo Objetivo Avaliar a presença de isquemia na porção distal das mãos dos membros superiores com Fistula Arteriovenosa (FAV) de pacientes em Terapia Renal Substitutiva (TRS) através da termografia por infravermelho. Método Amostra composta por 15 pacientes em TRS por hemodiálise por meio de FAV que responderam um questionário elaborado pelos próprios autores com as seguintes variáveis: dados sociodemográficos, diagnóstico, sinais vitais e dados sobre a FAV. Para obtenção dos termogramas das mãos com e sem FAV foi utilizado uma câmera termográfica por infravermelho C5, FLIR Systems, fixada a 50 cm das mãos dos participantes, privilegiando o enquadramento bilateral enquadrando ambas as mãos. Os dados obtidos foram organizados em planilha de Excel 2011® e comparados estatisticamente utilizando o programa Microcal Origin 6.0, para avaliar se existia diferença entre as médias de temperatura. Resultados Com relação as variáveis sociodemográficas, o gênero masculino foi o predominante, faixa etária com média de 45 anos, ensino fundamental (incompleto/completo), casados e provenientes de outros municípios. A termografia demonstrou que há diferença de temperatura entre as mãos com FAV e sem FAV, com variação na temperatura de 1,78°C (± DP 1,99°C), menor para as mãos com FAV. Conclusão A análise da distribuição do sangue das mãos por meio da termografia pode fornecer evidências sobre a microcirculação periférica e orientar o diagnóstico precoce e o tratamento da isquemia induzida por FAV em indivíduos em TRS, como ferramenta inovadora de diagnóstico auxiliar das complicações dos acessos venosos de pacientes em hemodiálise.

Resumen Objetivo Evaluar la presencia de isquemia en la parte distal de las manos de los miembros superiores con fístula arteriovenosa (FAV) de pacientes en terapia de reemplazo renal (TRR) a través de la termografía infrarroja. Métodos Muestra compuesta por 15 pacientes en TRR por hemodiálisis mediante FAV que respondieron un cuestionario elaborado por los propios autores con las siguientes variables: datos sociodemográficos, diagnóstico, signos vitales y datos sobre la FAV. Para obtener los termogramas de las manos con y sin FAV, se utilizó una cámara termográfica infrarroja C5, FLIR Systems, ubicada a 50 cm de las manos de los participantes, favoreciendo el encuadramiento bilateral y encuadrando ambas manos. Los datos obtenidos se organizaron en una planilla de Excel 2011® y se compararon estadísticamente con el programa Microcal Origin 6.0, para evaluar si había diferencia entre los promedios de temperatura. Resultados Con relación a las variables sociodemográficas, el género masculino fue predominante, grupo de edad promedio de 45 años, educación primaria (incompleta/completa), casados y provenientes de otros municipios. La termografía demostró que hay diferencia de temperatura entre las manos con FAV y sin FAV, con una variación de temperatura de 1,78°C (± DP 1,99°C), menor en las manos con FAV. Conclusión El análisis de la distribución de la sangre de las manos por medio de termografía puede ofrecer evidencias sobre la microcirculación periférica y guiar el diagnóstico temprano y el tratamiento de la isquemia inducida por FAV en individuos en TRR, como una herramienta innovadora de diagnóstico auxiliar de las complicaciones de los accesos vasculares de pacientes en hemodiálisis.

Abstract Objective To assess the presence of ischemia in the distal portion of the hands of the upper limbs with arteriovenous fistula (AVF) in patients undergoing renal replacement therapy (RRT) using infrared thermography. Method The sample consisted of 15 patients on RRT via hemodialysis using an AVF who answered a questionnaire prepared by the authors themselves with sociodemographic data, diagnosis, vital signs and data on AVF. To obtain thermograms of hands with and without AVF, a C5 infrared thermographic camera, FLIR Systems, was used, fixed 50 cm from participants' hands, favoring bilateral framing of both hands. The data obtained were organized in an Excel 2011® spreadsheet and statistically compared using the Microcal Origin 6.0 program to assess whether there was a difference between temperature averages. Results Regarding sociodemographic variables, males were predominant, with a mean age of 45 years, (incomplete/complete) elementary school, married and from other municipalities. Thermography demonstrated that there is a difference in temperature between hands with AVF and without AVF, with a temperature variation of 1.78°C (± SD 1.99°C), lower for hands with AVF. Conclusion The analysis of hand blood distribution using thermography can provide evidence on peripheral microcirculation and guide the early diagnosis and treatment of AVF-induced ischemia in individuals undergoing RRT as an innovative auxiliary diagnostic tool for complications of venous access in hemodialysis patients.

Cardiovascular Disease in Latin American Women Gaps and opportunities

Abstract Cardiovascular disease (CVD) remains the leading cause of death in women. This review will address the known disparities in cardiovascular care concerning diagnosing and treating of heart disease in Latin American (LA) women. Gender-specific differences regarding the incidence, treatment, and outcomes of common cardiovascular pathology are increasingly recognized. Today, we identify that women have cardiovascular risk factors (CRFs), specifying the traditional, emerging, unique, or sex-specific determinants and the social and biological determinants that play a leading role in the prevention of CVD. The purpose of this article is to review the literature on cardiovascular disease in LA women, focusing on ischemic heart disease (IHD), valve disease (VD), heart failure, and cardiac rehabilitation (CR), where disparities continue to affect outcomes. Understanding the unique cardiovascular risk profile and barriers to optimal treatment outcomes in women is imperative to eliminate the current disparities in CVD.

Open revascularization for chronic mesenteric ischemia in the endovascular era: a quaternary-center experience and management algorithm / Revascularização aberta na isquemia mesentérica crônica durante a era endovascular: experiência de um centro quaternário e um algoritmo de tratamento

Abstract Background Chronic mesenteric ischemia (CMI) is a debilitating disease with a heavy burden on quality of life. Stenting of the superior mesenteric artery (SMA) is the first option for treatment, but there is a lack of consensus defining precise indications for open revascularization (OR). Objectives To describe a series of 4 patients with CMI treated with OR and to present an algorithm for the management of this condition. Methods Three patients presented with typical intestinal angina and weight loss. One patient was subjected to prophylactic revascularization during open abdominal aortic aneurysm repair. Surgical techniques included: 1) Bypass from the infrarenal aorta to the SMA; 2) Bypass from an aorto-bifemoral polyester graft to the SMA; 3) Bypass from the right iliac artery to the SMA; 4) Bypass from the right graft limb of an aorto-biiliac polyester graft to the median colic artery at Riolan's arcade. PTFE was used in all surgeries. All grafts were placed in a retrograde configuration, tunneled under the left renal vein, making a smooth C-loop. A treatment algorithm was constructed based on the institution's experience and a review of recent literature. Results All patients demonstrated resolution of symptoms and recovery of body weight. All grafts are patent after mean follow-up of two years. Conclusions Open revascularization using the C-loop configuration is a valuable technique for CMI and may be considered in selected cases. The algorithm constructed may help decision planning in other quaternary centers.

Resumo Contexto A isquemia mesentérica crônica (IMC) é uma doença debilitante, com grave impacto na qualidade de vida. A literatura recomenda a angioplastia com stent da artéria mesentérica superior (AMS) como primeira opção de tratamento, mas há falta de consenso que defina indicações precisas para a revascularização aberta. Objetivos Descrever uma série de quatro pacientes com IMC, tratados com revascularização aberta, e apresentar um algoritmo para o manejo dessa condição. Métodos Três pacientes apresentaram angina intestinal típica e perda ponderal. Uma paciente foi submetida a reparo aberto de aneurisma da aorta abdominal e apresentava obstrução da AMS, que foi revascularizada profilaticamente. As técnicas cirúrgicas incluíram: 1) enxerto entre a aorta infrarrenal e a AMS; 2) enxerto entre o dácron utilizado em um enxerto aortobifemoral e a AMS; 3) enxerto entre a artéria ilíaca comum direita e a AMS; e 4) enxerto entre o ramo direito do dácron utilizado em um enxerto aorto-biilíaco e a artéria cólica média (ao nível da arcada de Riolan). Todos os enxertos foram feitos utilizando politetrafluoretileno em uma configuração retrógrada, tunelizados abaixo da veia renal esquerda, fazendo uma alça em C. Resultados Todos os pacientes demonstraram resolução dos sintomas e ganho ponderal. Todos os enxertos se mantiveram pérvios durante um seguimento médio de 2 anos. Conclusões A revascularização aberta para IMC utilizando-se a alça em C é uma técnica valiosa e pode ser considerada em pacientes selecionados. O algoritmo proposto pode auxiliar na decisão terapêutica em centros quaternários.

Correlação entre o índice de resistência vascular e a arteriografia na avaliação do leito arterial distal na isquemia crítica dos membros inferiores / Correlation between the vascular resistance index and arteriography for assessment of the distal arterial bed in chronic limb threatening ischemia

Resumo Contexto Pacientes com isquemia crítica (IC) dos membros inferiores (MMII) precisam de arteriografia para o planejamento da cirurgia de revascularização. A ultrassonografia Doppler (UD) não é invasiva e, através da aferição do índice de resistência (IR), pode fornecer informações sobre as artérias distais. Objetivos Correlacionar a Classificação Angiográfica de Rutherford com o IR na avaliação do leito arterial distal dos MMII. Métodos Estudo transversal, realizado em hospital público terciário, com 120 pacientes portadores de IC dos MMII, entre setembro de 2019 a abril de 2022. Foi comparado o IR das artérias da perna passíveis de serem receptoras de revascularização com a imagem obtida através da arteriografia dessas artérias em acordo com a Classificação Angiográfica de leito distal de Rutherford. Resultados Foram avaliados 120 MMII em 120 pacientes com idade média de 68,6 anos. A amostra foi composta de 50,0% de pacientes do sexo masculino. Na amostra, 90,0% pacientes encontravam-se na classe cinco de Rutherford. Os valores do IR encontrados para as artérias de perna apresentaram uma correlação positiva, estatisticamente significativa, quando comparados com a Classificação de Rutherford (tibial anterior, p< 0,01; tibial posterior, p = 0,012 e fibular, p = 0,034 e artéria dorsal do pé, p < 0,001). Conclusões Neste estudo, os IRs das artérias da perna obtidos através da ultrassonografia Doppler apresentaram uma correlação positiva quando comparados à classificação de Rutherford. Em pacientes com isquemia crítica, esse índice pode ser útil na avaliação do leito arterial distal dos membros inferiores.

Abstract Background Patients with chronic limb threatening ischemia (CLTI) of the lower limbs (LL) undergo arteriography for revascularization surgery planning. Doppler ultrasound (DU) is non-invasive and can provide information about the distal arteries through measurement of the resistance index (RI). Objectives To correlate the Rutherford Angiographic Classification with the RI for assessment of the distal arterial bed of the LL. Methods A cross-sectional study, conducted at a public tertiary hospital with 120 patients with LL CLTI, from September 2019 to April 2022. The RI of arteries that were candidates for revascularization was compared with the images of the same arteries obtained using arteriography, using the Rutherford Angiographic Classification of the distal bed. Results A total of 120 LL were assessed in 120 patients with a mean age of 68.6 years. The sample was 50.0% male and 90.0% of the patients in the sample were classified as Rutherford category five. The RI values found for the arteries of the leg exhibited a statistically significant positive correlation with the Rutherford Classification (anterior tibial, p< 0.01; posterior tibial, p = 0.012 fibular, p = 0.034; and dorsalis pedis, p < 0.001). Conclusions In this study, RIs for the arteries of the leg measured using Doppler ultrasound exhibited a positive correlation with the Rutherford Classification. This index could be useful for assessment of the distal arterial bed of the lower limbs of patients with chronic limb threatening ischemia.

Feasibility of Goal-Directed Fluid Therapy in Patients with Transcatheter Aortic Valve Replacement - An Ambispective Analysis

ABSTRACT Introduction: Goal-directed fluid therapy (GDFT) has been shown to reduce postoperative complications. The feasibility of GDFT in transcatheter aortic valve replacement (TAVR) patients under general anesthesia has not yet been demonstrated. We examined whether GDFT could be applied in patients undergoing TAVR in general anesthesia and its impact on outcomes. Methods: Forty consecutive TAVR patients in the prospective intervention group with GDFT were compared to 40 retrospective TAVR patients without GDFT. Inclusion criteria were age ≥ 18 years, elective TAVR in general anesthesia, no participation in another interventional study. Exclusion criteria were lack of ability to consent study participation, pregnant or nursing patients, emergency procedures, preinterventional decubitus, tissue and/or extremity ischemia, peripheral arterial occlusive disease grade IV, atrial fibrillation or other severe heart rhythm disorder, necessity of usage of intra-aortic balloon pump. Stroke volume and stroke volume variation were determined with uncalibrated pulse contour analysis and optimized according to a predefined algorithm using 250 ml of hydroxyethyl starch. Results: Stroke volume could be increased by applying GDFT. The intervention group received more colloids and fewer crystalloids than control group. Total volume replacement did not differ. The incidence of overall complications as well as intensive care unit and hospital length of stay were comparable between both groups. GDFT was associated with a reduced incidence of delirium. Duration of anesthesia was shorter in the intervention group. Duration of the interventional procedure did not differ. Conclusion: GDFT in the intervention group was associated with a reduced incidence of postinterventional delirium.

Cyanobacteria for cardiomyocyte protection against miocardial ischemia injury: a systematic review of animal and in vitro studies / Cianobactérias para a proteção de cardiomiócitos contra lesões isquêmicas miocárdicas: uma revisão sistemática de estudos em animais e in vitro

Objective: To perform a systematic review on using Cyanobacteria for protecting the cardiac tissue against damage caused by ischemia.Methods: this review encompasses in vitro and controlled animal experimental studies. Results: the results show that in general there are two types of interventions for treatment of ischemia and Ischemia/Reperfusion (IR) in cardiac tissue: (1) extracts treatments and (2) injection of Cyanobacteria in the damaged tissues. Extract treatments are based on the antioxidant potential of Cyanobacteria, and the studies focus mainly on Spirulina (Arthrospira platensis). The direct injection methods are based on the high capacity of these organisms to release oxygen during photosynthesis. Synechococcus elongatus is the Cyanobacteria species most commonly utilized in injections, either delivered independently or carried by hydrogels or nanoparticles. The direct Cyanobacteria injections are innovative techniques which can promote protection against apoptosis and have shown promising results, however, further research is necessary to refine the techniques and improve overall efficacy. Conclusion: the effects of these treatments were beneficial considering that the antioxidant effects of Cyanobacteria ameliorate blood biochemical markers and reduce damaged cardiac areas. The oxygen releasing of Cyanobacteria in the cardiac tissue also promoted recovery of cardiac tissue after ischemia or IR

Objetivo: realizar uma revisão sistemática sobre o uso de cianobactérias para proteção do tecido cardíaco contra danos causados pela isquemia. Métodos: esta revisão abrange estudos experimentais in vitro e estudos controlados em animais. Resultados: os resultados indicam que, em geral, existem dois tipos de intervenções para o tratamento de isquemia e isquemia/reperfusão (IR) no tecido cardíaco: (1) tratamentos com extratos e (2) injeção de cianobactérias nos tecidos danificados. Os tratamentos com extratos baseiam-se no potencial antioxidante das cianobactérias, e os estudos concentram-se principalmente em Spirulina (Arthrospira platensis). Os métodos de injeção direta são fundamentados na alta capacidade desses organismos de liberar oxigênio durante a fotossíntese. Synechococcus elongatus é a espécie de cianobactéria mais comumente utilizada em injeções, seja entregue de forma independente ou transportada por hidrogéis ou nanopartículas. As injeções diretas de cianobactérias são técnicas inovadoras que podem promover proteção contra a apoptose e mostraram resultados promissores, no entanto, mais pesquisas são necessárias para aprimorar as técnicas e melhorar a eficácia geral. Conclusão: os efeitos desses tratamentos foram benéficos, considerando que os efeitos antioxidantes das Cianobactérias melhoram os marcadores bioquímicos sanguíneos e reduzem as áreas cardíacas danificadas. A liberação de oxigênio pelas cianobactérias no tecido cardíaco também promoveu a recuperação do tecido após isquemia ou IR

Effects of gastrodin on the expression of BDNF and IL-6 in the striatum of rats with cerebral ischemia / 中国临床药理学与治疗学

AIM: To investigate the effect of gastrodin on the expression of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in the striatum of cerebral ischemia rats, and to explore the potential mechanism of gastrodin in treating cerebral ischemia. METHODS: The rats were randomly divided into four groups: normal, sham, model, and gastrodin groups, each consisting of 10 rats. After successful modeling using middle cerebral artery occlusion (MCAO), the gastrodin group received intraperitoneal injection of gastrodin injection at a dose of 10 mg/kg once a day for 14 consecutive days. Pathological changes in striatal neurons were observed using Nissl staining. Immunohistochemistry was utilized to detect positive expression of BDNF and IL-6 proteins in the striatum. Additionally, immunoblot analysis was performed to determine the expression levels of BDNF and IL-6 proteins in the striatum. RESULTS: Nissl staining revealed clear and intact structures of striatal neurons in the normal and sham groups, with tightly arranged cells. In the model group, the number of cells was significantly reduced compared to the sham group (P0.05). Compared to the sham group, the model group showed a decrease in the protein expression level of BDNF in the striatum on the ischemic side (P<0.01) and an increase in the protein expression level of IL-6 (P<0.05, P<0.01). In contrast, the gastrodin group showed an increase in the protein expression level of BDNF in the striatum on the ischemic side (P<0.05, P<0.01) and a decrease in the protein expression level of IL-6 (P< 0.05, P<0.01) compared to the model group. CONCLUSION: Gastrodin has a significant protective effect on striatal injury caused by cerebral ischemia, and its mechanism may be related to the up-regulation of the anti-inflammatory factor BDNF and the down-regulation of the pro-inflammatory factor IL-6.

Geraniol attenuates cerebral ischemia-reperfusion injury in rats by regulating oxidative stress via Nrf2/HO-1 pathway / 中国药理学通报

Aim To investigate the regulatory effect of geraniol on Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion(I/R)in rats. Methods In this experiment,all the male SD rats were randomly divided into nine groups receiving the following treatments:sham operation(sham); sham operation+200 mg·kg-1 geraniol; I/R; I/R+50 mg·kg-1 geraniol; I/R+100 mg/kg geraniol; I/R+200 mg·kg-1 geraniol; edaravone; I/R+ brusatol(Nrf2 inhibitor); I/R+200mg·kg-1 geraniol+brusatol. All rats received intraperitoneal injection of geraniol for five consecutive days before MCAO and again after MCAO. During the construction of cerebral I/R injury models,the blood vessels were isolated without any suture in the sham operation and the sham operation +200 mg·kg-1 geraniol groups while the blood vessels with suture in other groups. The damage of neurological function was evaluated by the modified rating scale for neurological function. The TTC,HE and Tunel staining methods were used to determine the cerebral infarction volume,the damage of the ischemic cortex and the apoptosis of cortical cells,respectively. The oxidative stress-related parameters then were measured. The protein expressions of Nrf2 and HO-1 were detected by immunohistochemical staining and the target protein expressions of the injured cortex were detected by Western blot. Results Compared with the model group,it was found that the geraniol treatment significantly repaired neural injury,reduced cerebral infarction volume,cerebral cortex damage and cell apoptosis. Meanwhile,geraniol intervention could significantly increase the expression of Nrf2/HO-1 protein in the right-sided cortex and reduce oxidative stress level. Conclusion Geraniol can attenuate cerebral injury induced by ischemia-reperfusion in rats via activating Nrf2/HO-1 signaling pathway.

Dynamic changes in cytoskeletal elements following acute cerebral ischemia and reperfusion in rats / 中国药理学通报

Aim To investigate the dynamic time-course changes in neuronal cytoskeleton after acute ischemia and reperfusion in rats. Methods Reperfusion was performedin rats by blocking the middle cerebralarteryfor 90 min, then therats wereobserved and collected at different time points. The brain damage wasobserved by Nissl staining,and neurobehavioural function was evaluated with neurological deficit score and forelimb placement test. The cellular changes in the alternations of cytoskeletal elements including microtubule associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) were observed by immunohistochemistry staining and Western blot. Impaired axons, dendrites and cytoskeletal alternations were detected by electron microscope. Results Brain damage and neurobehavioural function were gradually aggravated with the prolongation of reperfusion. Brain damage appeared earlier and more severe in striatum than in cortex. Moreover, decreased MAP2-related and increased NF-H-related immunoreactive intensities were found in the ischemic areas. Impaired cytoskeletal arrangement and reduced dense were indicated. Damaged cytoskeletal components such as microtubules and neurofilament arrangement, decreased axonal filament density, and swelled dendrites were observed after cerebral ischemia reperfusion by ultrastructural observations. Conclusions Different brain regions have diverse tolerance to ischemia-reperfusion injury. Major elements of neuronal cytoskeleton show dynamic responses to ischemia and reperfusion, which may further contribute to brain damage and neurological impairment following MCAO and reperfusion.

Effect of alisol A on cerebral ischemia reperfusion injury by protecting blood brain barrier and its mechanism / 中国药理学通报

Aim To investigate whether alisol A (AA) could improve the blood brain barrier (BBB) mediated cortex cerebral ischemia-repeifusion injury (CIRI) by inhibiting matrix metalloproteinase 9 (MMP-9). Methods The global cerebral ischemia- reperfusion (GCI/R) model in mice was established, and the AA was intragastric injected subsequently for seven days. The modified neurological severity scores (mNSS), open field test and Y-maze test were applied to detect neurological function. Magnetic resonance spectroscopy (MRS) was used to detect relevant neu- rosubstance metabolism in cortex of mice. Transmission electron microscope (TEM) was employed to observe the ultrastructure of BBB in cortex. Western blot and immunohistochemistry were used to detect the MMP-9 level in cortex. The binding possibility of A A and MMP-9 was determined by molecular docking. Results Compared with Sham group, mice in GCI/R group have an increased mNSS score but decreased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01). While mice in GCI/R + AA group have a decreased mNSS score but increased at total distance and center distance to total distance ratio in open field test as well as alternation rate in Y-maze test (P<0.01) compared with GCI/R group. MRS results found that in cortex of GCI/R group mice, the level of GABA and NAA significantly decreased while the Cho, mI and Tau level increased (P<0.01). Whereas in GCI/R + AA group mice, the GABA and NAA level increased and the Cho, ml and Tau decreased significantly (P<0.01). By TEM we observed that the basilemma of cerebral microvessels collapsed, the lumen narrowed, the endothelial cells were active and plasma membranes ruffled, gaps between cells were enlarged and tight junctions were damaged and the end feet of astrocytes were swollen in GCI/R group mice. While in GCI/R + AA group mice, the lumen was filled, plasma membranes of endothelial cells were smooth, tight junctions were complete and end feet of astrocytes were in normal condition. Western blot and immunohistochemistry both found that the MMP-9 level increased in GCI/R group mice (P < 0.01) and decreased in GCI/R + AA group mice (P < 0.05). Molecular docking proved the binding between aliso A and MMP9 through TYR-50 and ARG-106, and the binding energy was calculated as -6.24 kcal · mol

Protective effect and mechanism of Longshengzhi capsules on cerebral ischemia-reperfusion injury in rats / 中国药房

OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion （MCAO） was established by using the improved thread occlusion method. The experiment was divided into six groups： sham surgery group （only separating blood vessels without inserting thread plugs， given the same volume of normal saline）， model group （modeling， given the same volume of normal saline）， nimodipine group （positive control， modeling， dose of 20 mg/kg）， and low-dose， medium-dose， and high-dose groups of Longshengzhi capsules （modeling， doses of 0.72， 1.44 and 2.88 g/kg， respectively）， with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage， once a day， for 7 consecutive days. One hour after the last administration， the Zea Longa scoring method was used to score the neurological deficits in each group of rats， and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rats； TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4， NLRP3 and phosphorylated NF-κB （p-NF-κB） protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group， the neural dysfunction score， serum levels of TNF-α and IL-6， cerebral infarction volume ratio， relative expression levels of NF-κB and TLR4 mRNA， as well as protein relative expressions of TLR4， NLRP3 and p-NF-κB in the brain tissue， and relative protein expression of intracellular NF-κB were increased significantly in the model group （P＜0.01）； the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats， with a large amount of inflammatory cell infiltration； the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group， the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules， as well as the Nimodipine group， were reversed to varying degrees， and most differences were statistically significant （P＜0.05 or P＜0.01）； the pathological morphology observation showed a significant improvement， and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response， thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.

Individualized surgical treatment strategy for children with anomalous aortic origin of coronary artery / 中国胸心血管外科临床杂志

@#Objective To summarize and explore the individualized surgical treatment strategy and prognosis of anomalous aortic origin of coronary artery (AAOCA). Methods The clinical data of children with AAOCA admitted to Shanghai Children's Medical Center from March 2018 to August 2021 were retrospectively analyzed. Results A total of 17 children were enrolled, including 13 males and 4 females, with a median age of 88 (44, 138) months and a median weight of 25 (18, 29) kg. All patients received operations. The methods of coronary artery management included coronary artery decapitation in 9 patients, coronary artery transplantation in 5 patients and coronary artery perforation in 3 patients. One patient with severe cardiac insufficiency (left ventricular ejection fraction 15%) received mechanical circulatory assistance after the operation for 12 days. No death occurred in the early postoperative period, the average ICU stay time was 4.3±3.0 d, and the total hospital stay was 14.4±6.1 d. All the children received regular anticoagulation therapy for 3 months after discharge. The median follow-up time was 15 (13, 24) months. All patients received regular anticoagulation therapy for 3 months after discharge. No clinical symptoms such as chest pain and syncope occurred again. The cardiac function grade was significantly improved compared with that before operation. Imaging examination showed that the coronary artery blood flow on the operation side was unobstructed, and no restenosis occurred. Conclusion AAOCA is easy to induce myocardial ischemia and even sudden cardiac death. Once diagnosed, operation should be carried out as soon as possible. According to the anatomic characteristics of coronary artery, the early effect of individualized surgery is satisfactory, and the symptoms of the children are significantly improved and the cardiac function recovers well in the mid-term follow-up.

Latest research and prospect of CD47 in kidney transplantation / 器官移植

CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.

Down-regulating XBP1s alleviates hypoxia/reoxygenation injury of renal tubular epithelial cells by inhibiting ITPR-mediated mitochondrial dysfunction / 器官移植

Objective To evaluate the effect of spliced X-box binding protein 1 (XBP1s) on hypoxia/reoxygenation (H/R) injury of mouse renal tubular epithelial cells and unravel underlying mechanism. Methods Mouse renal tubular epithelial cells were divided into adenovirus negative control group (Ad-shNC group), targeted silencing XBP1s adenovirus group (Ad-shXBP1s group), Ad-shNC+H/R group and Ad-shXBP1s+H/R group. The apoptosis level, mitochondrial reactive oxygen activity, mitochondrial membrane potential and mitochondrial calcium ion level were detected in each group. Chromatin immunocoprecipitation followed by sequencing (ChIP-seq) was employed to analyze the binding sites of XBP1s in regulating the inositol 1,4,5-trisphosphate receptor (ITPR) family. The expression levels of XBP1s and ITPR family messenger RNA (mRNA) and protein were determined in each group. Results Compared with the Ad-shNC group, the apoptosis level was higher, mitochondrial reactive oxygen species level was increased, mitochondrial membrane potential was decreased and mitochondrial calcium ion level was elevated in the Ad-shNC+H/R group. Compared with the Ad-shNC+H/R group, the apoptosis level was lower, mitochondrial reactive oxygen species level was decreased, mitochondrial membrane potential was elevated, and mitochondrial calcium ion level was decreased in the Ad-shXBP1s+H/R group (all P<0.05). Compared with the Ad-shNC group, relative expression levels of XBP1s, ITPR1, ITPR2 and ITPR3 mRNAs and proteins were down-regulated in the Ad-shXBP1s group (all P<0.05). Compared with the Ad-shNC group, relative expression levels of XBP1s, ITPR1, ITPR2 and ITPR3 proteins were up-regulated in the Ad-shNC+H/R group. Compared with the Ad-shNC+H/R group, relative expression levels of XBP1s, ITPR1, ITPR2 and ITPR3 were down-regulated in the Ad-shXBP1s+H/R group (all P<0.05). ChIP-seq results showed that XBP1s could bind to the promoter and exon of ITPR1, the exon of ITPR2, and the exon of ITPR3. Conclusions XBP1s may affect mitochondria-associated endoplasmic reticulum membrane structure and function by directly regulating ITPR transcription and translation. Down-regulating XBP1s may inhibit ITPR expression and mitigate mitochondrial damage.