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.

Evaluación angiográfica de la distribución anatómica de la irrigación sanguínea del ángulo esplénico del colon en población chilena

Objetivo: Identificar los patrones de distribución vascular del ángulo esplénico del colon (AEC) en la población chilena para su comparación con la literatura oriental (Fukuoka). Materiales y Métodos: Estudio descriptivo, transversal. Se caracterizó la irrigación del AEC de imágenes con protocolo Urotac realizadas en Clínica INDISA entre el año 2020 y 2021 (n = 127), clasificándolas dentro de 6 tipos descritos por Fukuoka. Se evaluaron características demográficas y comorbilidades. Las variables fueron analizadas utilizando estadística descriptiva y la significancia mediante la prueba Chi2. Resultados: Existen diferencias en los tipos irrigación del AEC entre la serie local y Fukuoka, la irrigación tipo 3 fue la que presentó mayor variación (p < 0,05). El tipo 1 es la más frecuente (34,7%), sin casos del Tipo 4. No se identificó diferencia entre los distintos tipos de irrigación con relación a las variables demográficas y comorbilidades. Discusión: Al comparar nuestra serie con la oriental se evidenció similar frecuencia en tipos 1 y 6, mayor en tipos 3 y 5, y tipos 2 y 4 con menor representación. Se identificó un mayor aporte en la irrigación del AEC por la arteria cólica izquierda (ACI) en la población estudiada (64,6%). Conclusión: Nuestra población tiene mayor participación de ACI en irrigación del AEC que orientales (64,6% vs 49,6%), los tipos más frecuentes son 1, 3 y 6, el Tipo 1 es la forma más frecuente de irrigación, similar a Fukuoka (34,7% vs 39,7%), Tipo 3 tiene mayor representación en nuestra población que en la oriental (29,9% vs 9,9%).

Objective: To identify the vascular distribution patterns of the splenic flexure of the colon (AEC) in the Chilean population for comparison with the oriental literature (Fukuoka). Methods: Descriptive, cross-sectional study. The irrigation of the AEC of images with the Urotac protocol performed at the INDISA Clinic between 2020 and 2021 (n = 127) was characterized, classifying them into 6 types described by Fukuoka. Demographic characteristics and comorbidities were evaluated. Variables were analyzed using descriptive statistics and significance using the Chi2 test. Results: There are differences in the types of irrigation of the AEC between the local series and Fukuoka, irrigation type 3 was the one that presented the greatest variation (p < 0.05). Type 1 is the most frequent (34.7%), with no cases of Type 4. No difference was identified between the different types of irrigation in relation to demographic variables and comorbidities. Discussion: When comparing our series with the eastern one, a similar frequency was found in types 1 and 6, higher in types 3 and 5, and types 2 and 4 with less representation. A greater contribution was identified in the irrigation of the AEC by the left colic artery (ICA) in the population studied (64.6%). Conclusion: Our population has a greater participation of ICA in AEC irrigation than Orientals (64.6% vs 49.6%), the most frequent types are 1, 3 and 6, Type 1 is the most frequent form of irrigation, similar to Fukuoka (34.7% vs 39.7%), Type 3 is more represented in our population than in the eastern one (29.9% vs 9.9%).

ACUTE MESENTERIC ISCHEMIA DUE TO SMA THROMBOSIS- A CASE REPORTS

INTRODUCTION:Acute mesenteric ischemia usually presents as abdominal pain that is out of proportion inrelation to tenderness; persistent vomiting, bloody diarrhea and shock. Sloughing of intestinal mucosa takes 3 hourswhile infarction of entire bowel thickness occurs in 6 hours. [1]- [3] CECT abdomen with mesenteric angiography isinvestigation of choice. If patient has presented after 24-48 hours, gangrene might have already occurred, resectionand anastomosis is done majority of cases with removal of vascular block under Doppler guidance or Injection ofpapaverine. Minimum bowel length required to be retained is 1.2 meters, otherwise the patient will have highmortality due to short bowel syndrome. [4]- [7]AIMS AND OBJECTIVES 1 ] To compare the surgical findings in various case scenarios having differentpresentations, patient factors and time of presentations with SMA thrombosis 2 ]To compare outcomes of surgicalintervention in different case scenariosCONCLUSION:SMA thrombosis was seen in non-covid time as well. Hypercoagulable state which corresponds toraised d-dimer and FDP, the cases of mesenteric ischemia due to SMA thrombosis are seen more commonly incovid-19 era. This series draws to attention that timely diagnosis and appropriate surgery with resection and properfollow up with anti-coagulant the morbidity and mortality is averted. Acute mesenteric ischemia is commonly due toemboli (45-50%) rather than thrombosis (20-25%). Non occlusive disease (5-15%) can be due to various causes e.g.,pancreatitis, sepsis, heart failure, etc. Early diagnosis is the key to successful management. Aggressive resuscitation,early revascularization with vascular intervention and exploratory laparotomy is done if evidence of peritonitis ispresent.[8]-[9] Postoperative fluid management due to short bowel syndrome and appropriate antibiotic coverage isnecessary to revive the patient. Long term TPN support for patients with short bowel patients is necessary. They arecandidates for intestinal transplantation if survived.[10]

Comparison of high or low inferior mesenteric artery ligation in laparoscopic anterior resection of rectum based on CT precise guidance / 中国医师进修杂志

Objective:To compare the advantages of high or low inferior mesenteric artery (IMA) ligation in laparoscopic anterior resection of rectum based on CT precise guidance.Methods:One hundred and twenty patients with rectal cancer who underwent laparoscopic anterior resection of rectum in Shanghai Sixth People′s Hospital South Campus from January 2016 to June 2020 were selected. Surgical protocol was selected according to the principle of voluntariness. Sixty-eight cases underwent high IMA ligation (high IMA ligation group), and 52 cases underwent low IMA ligation (low IMA ligation group). The perioperative conditions (operative time, intraoperative blood loss, postoperative anal exhaust time, abdominal drainage, hospitalization time and ileostomy), postoperative pathological data (proximal margin distance, distal margin distance, total number of dissected lymph nodes and number of positive lymph nodes) and postoperative recovery (anastomotic stoma fistula, urinary retention, sexual dysfunction and daily number of defecation) were recorded. The quality of life 6 months after surgery was evaluated by the quality of life instruments for colorectal cancer scale (QLQ-CR38). Patients were followed up for 6 to 36 months, and the local recurrence and distant metastasis were recorded.Results:The postoperative anal exhaust time in low IMA ligation group was significantly shorter than that in high IMA ligation group: (2.87 ± 1.04) d vs. (3.26 ± 1.00) d, and there was statistical difference ( P<0.05); there were no statistical differences in operative time, intraoperative blood loss, abdominal drainage, hospitalization time and rate of ileostomy between 2 groups ( P>0.05). There were no statistical difference in proximal margin distance, distal margin distance, total number of dissected lymph nodes and number of positive lymph nodes between 2 groups ( P>0.05). The incidences of anastomotic stoma fistula, urinary retention and sexual dysfunction in low IMA ligation group were significantly lower than those in high ligation group: 3.85% (2/52) vs. 13.24% (9/68), 3.85% (2/52) vs. 11.76% (8/68) and 5.77% (3/52) vs. 14.71% (10/68), the daily number of defecation was significantly less than that in high ligation group: (2.87 ± 0.98) times vs. (4.05 ± 1.56) times, and there were statistical differences ( P<0.05 or <0.01). The functional dimension, symptom dimension and aggregate score of QLQ-CR38 in low IMA ligation group were significantly higher than those in high ligation group: (15.46 ± 4.22) scores vs. (13.68 ± 3.56) scores, (51.82 ± 13.54) scores vs. (45.65 ± 12.42) scores and (67.28 ± 14.28) scores vs. (59.33 ± 12.85) scores, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the rates of local recurrence and distant metastasis between 2 groups ( P>0.05). Conclusions:The application of low IMA ligation based on CT precise guidance in laparoscopic anterior resection of rectum can obtain the same surgical effect as the high IMA ligation. It can promote the recovery of gastrointestinal function after surgery, reduce the risk of complications, have less effect on the defecation function, which can improve the life quality after the surgery.

Avaliação de mecanismos de modificação pós-traducional da óxido nítrico sintase endotelial (eNOS) associados a biodisponibilidade do óxido nítrico em artérias de ratas espontaneamente hipertensas (SHR) ao final da prenhez / Evaluation of post-translational modification mechanisms of endothelial nitric oxide synthase (eNOS) associated with the nitric oxide bioavailability in arteries from spontaneously hypertensive rats (SHR) in the end of pregnancy

A redução da reatividade vascular à fenilefrina (PE) em aorta de ratas espontaneamente hipertensas (SHR) ao final da prenhez é dependente de maior produção e/ou maior biodisponibilidade de óxido nítrico (NO), consequente do aumento da fosforilação da enzima óxido nítrico sintase endotelial (eNOS) via PI3K/Akt. A glicosilação do tipo N-acetil-glucosamina (O-GlcNAc) é uma modificação pós-traducional que compete com a fosforilação pelos mesmos sítios de ligação nas proteínas. A O-GlcNAcilação da eNOS em serina1177 leva a redução da sua atividade enquanto a fosforilação leva a sua ativação. Além destes mecanismos, a interação da eNOS com outras proteínas é capaz de regular positiva ou negativamente a sua atividade. O objetivo deste trabalho foi analisar possíveis alterações nos mecanismos de modificação pós-traducional que controlam a ativação da eNOS os quais poderiam contribuir para maior ativação e maior biodisponibilidade de NO observada em artérias de ratas prenhes. Foram avaliados o conteúdo proteico O-GlcNAc e também expressão das enzimas que participam desta modificação, O-GlcNAc transferase (OGT) e O-GlcNAcase (OGA) por Western Blotting e a atividade da OGA por ensaio bioquímico em aorta e em artéria mesentérica (2º ou 3º ramo) de ratas não prenhes (NP) e prenhes (P), normotensas (Wistar) e SHR. Ensaios de Western Blotting foram realizados também para análise da expressão das seguintes proteínas: Cav-1, p-Cav-1, CaM e Hsp90. Realizamos a contagem do número de cavéolas endoteliais da aorta e da artéria mesentérica na presença ou ausência da metil-ß-ciclodextrina (dextrina, 10 mmol/L) por microscopia eletrônica. Em estudos funcionais, avaliamos a participação da enzima OGA, pela inibição com PugNAc (100 µmol/L) e das cavéolas, utilizando um desorganizador de cavéolas, a dextrina (10 ou 20 mmol/L), na menor reatividade vascular à PE observada em aortas de ratas P. Observamos que o conteúdo de proteínas O-GlcNAciladas estava diminuído em aorta e em leito mesentérico de ratas Wistar P e SHR P. Apesar da expressão da OGT e da OGA não estar alterada, a atividade da OGA foi aumentada em aorta e leito mesentérico de ratas Wistar P, mas, encontra-se diminuída em aorta e aumentada em leito mesentérico de SHP P. A incubação com PugNAc reverteu a reduzida reatividade à PE em aorta e artéria mesentérica de ratas Wistar P mas este efeito não foi observado em vasos SHR P, demonstrando que a OGA parece ter um papel importante na redução da O-GlcNAcilação de proteínas vasculares em Wistar P. Em vasos incubados com PugNAc, a remoção do endotélio ou a incubação com L-NAME, não alterou significativamente a reatividade à PE. Juntos estes resultados sugerem que a maior atividade da eNOS observada em vasos de Wistar P, fica prejudicada na presença do PugNAc, e depende da atividade da OGA. Como não houve alteração da resposta contrátil à PE em vasos de SHR P incubados com PugNAc, possivelmente um mecanismo diferente, envolvendo a menor atividade da OGT, ocorre nestas artérias para a redução da O-GlcNAcilação da eNOS. A desorganização das cavéolas por meio da dextrina causou aumento de contração à PE e redução de potência da ACh em aortas de Wistar NP e SHR NP, porém não houve alteração em aortas de ratas Wistar P e SHR P. A dextrina não alterou o número de cavéolas em artérias de Wistar P e SHR P quando comparado com ratas NP. SHR NP apresentam um reduzido número de cavéolas das aortas em relação a Wistar NP bem como expressão reduzida de Cav-1, p-Cav-1 e CaM. A prenhez não foi capaz de alterar a expressão da Cav-1, CaM e Hsp90 em aorta e leito mesentérico de ratas normotensas e hipertensas. Estes resultados sugerem que a prenhez não altera a expressão das proteínas Cav-1, CaM e Hsp90 e possivelmente a interação com a eNOS em aorta e artérias mesentéricas de ratas normotensas e hipertensas. Em conclusão, entre os mecanismos estudados de modificação pós-traducional da eNOS, a redução da O-GlcNAcilação da eNOS, por mecanismos que envolvem a atividade da OGA e possivelmente da OGT, favoreceria a fosforilação da eNOS e consequente maior biodisponibilidade de NO, contribuindo desta forma para modulação da resposta contrátil da PE nas artérias de ratas P(AU)

Reduction of vascular reactivity to phenylephrine (PE) in aorta of spontaneously hypertensive rats (SHR) at the end of pregnancy is dependent on higher production and/or higer bioavailability of nitric oxide (NO), as a consequence of increased endothelial nitric oxide synthase enzyme (eNOS) phosphorylation, by PI3K/Akt. Glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification that competes with phosphorylation by the same binding sites in proteins. O-GlcNAcylation of eNOS on serine site leads to a reduction in its activity while eNOS phosphorylation leads to its activation. In addition to these mechanisms, the interaction of eNOS with other proteins is able to regulate positively or negatively its activity. The objective of this study was to analyze possible changes in the mechanisms of post-translational modification that control the eNOS activation, which could contribute to its the greater activation and greater bioavailability of NO observed in arteries of pregnant rats. The O-GlcNAc-protein content and also the enzymes expression that participate in this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) was assessed by Western Blotting, and OGA activity were evaluated by biochemical assay in the aorta and in the artery mesenteric (2nd or 3rd branch) of non-pregnant (NP) and pregnant (P), normotensive rats (Wistar) and SHR. Western Blotting assays were also performed for expression analysis of the following proteins: Cav-1, p-Cav-1, CaM and Hsp90. We performed the counting of the number of endothelial caveolae in the aorta and the mesenteric artery in the presence or absence of methyl-ß-cyclodextrin (dextrin, 10 mmol/L) by electronic microscopy. In functional studies, we evaluated the participation of the OGA enzyme, by inhibition with PugNAc (100 µmol/L) and of the caveolae, using a caveolae disassembler, dextrin (10 or 20 mmol/L), in the reduced vascular reactivity observed in aortas or mesenteric arteries of P rats. We observed that the content of O-GlcNAcylated proteins was decreased in the aorta and in the mesenteric bed of Wistar P and SHR P rats. Although OGT and OGA expression is not altered, OGA activity was increased in the aorta and mesenteric bed of Wistar P rats but was decreased in the aorta and increased in the mesenteric bed of SHP P. Incubation with PugNAc reversed the reduced reactivity to PE in the aorta and mesenteric artery of Wistar P but this effect was not observed in SHR P arteries, demonstrating that OGA appears to play an important role in reducing O-GlcNAcylation of vascular proteins in Wistar P. In arteries incubated with PugNAc, endothelial removal or incubation with L-NAME did not significantly alter reactivity to PE. Together, these results suggest that the greater eNOS activity observed in Wistar P vessels was impaired in the presence of PugNAc, and it depends on OGA activity. As there was no change in the contractile response to PE in SHR P arteries incubated with PugNAc, possibly a different mechanism, involving the lower activity of OGT, occurs in these vessels for the reduction of O-GlcNAcylation of eNOS. Dextrin caused increased contraction of PE and decreased ACh potency in Wistar NP and SHR NP aortas, but there was no change in aortas of Wistar P and SHR P. Dextrin did not alter the number of cavelae in Wistar P and SHR P arteries compared to NP rats. SHR NP showed a lower number of caveolae than to NP Wistar as well reduced expression of Cav-1 and CaM. Pregnancy was not able to alter the expression of Cav-1, CaM and Hsp90 in the aorta and mesenteric bed of normotensive and hypertensive rats. These results suggest that pregnancy does not alter the expression of Cav-1, CaM and Hsp90 proteins and possibly interaction with eNOS in the aorta and mesenteric arteries of normotensive and hypertensive rats. In conclusion, among the studied mechanisms of post-translational modification of eNOS, the reduction of O-GlcNAcylation of eNOS, by mechanisms that involve OGA activity and possibly OGT, would favor eNOS phosphorylation and consequent greater NO bioavailability, contributing in this way for modulation of the contractile response to PE in the arteries of P rats(AU)

Vasorelaxant activity and acute toxicity of the ethanolic extract of Zanthoxylum rhoifolium Lam leaves

The study evaluated the vasorelaxant effect induced by the ethanolic extract of the leaves of Zanthoxylum rhoifolium Lam (EEtOH-Zr/leaves). Wistar rats were treated with the leaf extract containing a single dose of 2,000 mg / kg, v.o. After 14 days, the animals were anesthetized for blood collection and subsequent analysis of the biochemical parameters; they were then euthanized (sodium pentobarbital-100 mg/kg, i.p.) for the removal and morphological analysis of the heart, lung, liver and kidney. The vasorelaxation activity the and vascular reactivity of EEtOH-Zr/leaves were evaluated on artery mesenteric rings isolated from rats. The extract showed no signs of toxicity and no significant difference in the values of the biochemical parameters between the control group and the group of treated animals. In the evaluation of pharmacological activity in the smooth muscle, the EEtOH-Zr/leaves caused vasorelaxant effect on the tonic contraction induced by phenylephrine in mesenteric artery preparations in the presence (pD2=2.17±0.05 µg/mL; Emax=99.8±5.2%) and absence (pD2=2.14±0.05 µg/mL; Emax=95.3±6.4%) of the vascular endothelium. Oral administration of EEtOH-Zr/leaves reduced the contraction induced by the cumulative addition of PHE. It is concluded that the EEtOH-Zr/leaves promote vasorelaxation and reduce vascular reactivity of adrenergic alpha-1 agonist in the mesenteric artery. The results did not show toxic effects of the extract.

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)

Effect of caveolin-1 expression on high-salt diet-induced endothelial dys-function in type 1 diabetic rats / 中国病理生理杂志

[ ABSTRACT] AIM: To investigate the underlying mechanisms responsible for endothelial dysfunction of type 1 diabetes mellitus (DM) rats fed with high-salt diet.METHODS:Type 1 DM was induced by intraperitoneal injection of streptozotocin (70 mg/kg).Normal and diabetic rats were fed high-salt food (HS, 8% NaCl) and standard food for 6 weeks, respectively.Isometric tension of the mesenteric arteries were measured .The expression of Akt , endothelial nitric oxide synthase (eNOS) and caveolin-1 (Cav-1) was examined by Western blot .RESULTS:The rats in DM+HS group exhibited more pronounced impairment of vasorelaxation to acetylcholine and insulin compared with either DM group or HS group (P<0.01).Akt and eNOS phosphorylation levels, and nitric oxide (NO) concentration in DM +HS group were significantly lower than those in DM group (P<0.01).The level of Cav-1 in DM+HS group was significantly higher than that in DM group and HS group .CONCLUSION:Impaired endothelial Akt activation , increased Cav-1 expression and re-sultant decreased eNOS activation contribute to aggravate high-salt diet-induced endothelial dysfunction and hypertension in DM rats.

Efeito vasorelaxante do doador de óxido nítrico [Ru(terpy)(bdq)NO]3+ (TERPY) em artéria de resistência e sua interação com a óxido nítrico sintase endotelial (eNOS) de Ratos Espontaneamente Hipertensos (SHR) / Vasorelaxation effect of nitric oxide donor [Ru(terpy)(bdq)NO]3+ (TERPY) on resistance artery and its interaction with endothelial nitric oxide synthase (eNOS) of Spontaneously Hypertensive Rats (SHR)

O TERPY promove efeito hipotensor de maior magnitude em ratos hipertensos (SHR e 2R-1C) do que em ratos normotensos (Wistar e 2R). Foi demonstrado anteriormente que o endotélio prejudica o efeito vasodilatador do TERPY em aorta de Wistar. No entanto, observamos que o endotélio melhora os efeitos vasodilatadores do TERPY em aorta de SHR. Vasos sanguíneos de menor calibre, tais como as artérias de resistência, estão associadas ao controle da resitência vascular periférica e da pressão arterial. Nossa hipótese é que o TERPY induz relaxamento nas artérias mesentéricas de resistência em SHR e que as células endoteliais modulam positivamente o efeito do TERPY nestes vasos sanguíneos. Portanto, o nosso objetivo foi avaliar o efeito vasodilatador do TERPY em anéis com e sem endotélio de artéria mesentérica de ratos SHR, o seu mecanismo de relaxamento e a participação da NOS sobre esse efeito. e a Nossos resultados mostraram que o TERPY induziu um efeito vasodilatador dependente da concentração em anéis de artérias mesentéricas (2º e 3º ramos) de SHR e de ratos Wistar. A potência do TERPY foi maior em anéis intactos do que em anéis sem endotélio em artérias mesentéricas de SHR, mas em Wistar o endotélio prejudicou o efeito do TERPY. Nas artérias mesentéricas sem endotélio de SHR, o efeito do TERPY é dependente da atividade da guanilato ciclase solúvel e de canais para potássio. Nas artérias mesentéricas intactas de SHR, o efeito de TERPY depende da atividade de eNOS, mas não é dependente das atividades de nNOS, iNOS ou da via da ciclooxigenase. O TERPY promove a fosforilação da eNOS nos resíduos de serina1177 e aumenta a concentração de óxido nítrico em células endoteliais isoladas de artérias mesentéricas de SHR. Nossos resultados mostraram que a guanilato ciclase solúvel, os canais para potássio e a eNOS estão envolvidos no efeito vasodilatador estimulado pelo TERPY nas artérias de resistência mesentérica de SHR. Numa segunda parte deste estudo, avaliamos o mecanismo de ação de TERPY e seu efeito sobre a atividade da eNOS em células endoteliais. As células HUVEC, WT-HEK e HEK-eNOS foram tratadas com TERPY em diferentes tempos (0 a 60 minutos). Foram analisados por Western blotting o efeito do TERPY sobre a fosforilação de eNOS, monômero e dímero da eNOS e sobre monômero e oligômero de caveolina-1. Também foi avaliado o efeito do TERPY na interação eNOS/Cav-1 através de co-imunoprecipitação. As alterações induzidas pelo TERPY sobre as concentrações de espécies reativas de oxigênio e peroxinitrito em células endoteliais foram medidas usando sonda DHE e biossensor 7-CBA, respectivamente. A concentração de óxido nítrico (NO) foi avaliada por sonda DAF-FM e sensor Cooper. O TERPY promoveu desacoplamento e disfunção da eNOS, dependente de BH4. A desestabilização dos oligômeros da caveolina-1 foi induzida pelo TERPY. Consequentemente, o TERPY reduziu a interação eNOS/Cav-1 e promoveu ativação da eNOS. Nossos resultados mostraram que a atividade da eNOS pode ser regulada de duas maneiras diferentes pelo TERPY. O TERPY promove desacoplamento e fosforilação da eNOS, promovendo uma estratégia diferente para a regulação da atividade desta enzima. As moléculas químicas ou biológicas como o TERPY que regulam a atividade da eNOS e aumentam a produção e a biodisponibilidade de NO teriam ações terapêuticas importantes para o tratamento de doenças vasculares associadas a hipertensão(AU)

TERPY promotes a hypotensive effect with greater magnitude in hypertensive rats (SHR and 2K-1C) than in normotensive rats (Wistar and 2K). Previously, it was demonstrated that endothelium impairs vasodilatory effect of TERPY in Wistar aorta. However, we observed that endothelium improves the vasodilatory effect of TERPY in SHR aorta. Smaller blood vessels, such as mesenteric arteries, are associated with the control of peripheral vascular resistance and blood pressure. We hypothesized that TERPY induces relaxation on mesenteric resistance arteries in SHR and endothelial cells modulate positively the TERPY's effect on these blood vessels. Therefore, our goal was to evaluate the vasodilator effect of TERPY in rings with and without endothelium of mesenteric arteries in SHR, the mechanism of relaxation and the participation of NOS on this effect. Our results show TERPY induced a concentration-dependent vasodilator effect in mesenteric arteries (2nd and 3 rd branches) rings from SHR and Wistar. The potency of TERPY was higher in intact than in denuded rings from SHR, but in Wistar, endothelium impair the TERPY's effect. In denuded mesenteric arteries from SHR, the relaxation effect induced by TERPY is dependent of soluble guanylate cyclase and activation of potassium channel. However, in intact mesenteric arteries from SHR, TERPY´s effect is modulated by eNOS activity, but it is not dependent of nNOS, iNOS or cyclooxygenase pathway activities. TERPY promotes eNOS3 Ser1177 phosphorylation and increases nitric oxide concentration in isolated endothelial cells of mesenteric arteries from SHR. Together, our results showed that soluble guanylate cyclase, potassium channels, and eNOS are involved in the vasodilator effect of TERPY in mesenteric resistance arteries from SHR. In a second part of this study, we aimed to evaluate the mechanism of action of TERPY and its effect on eNOS activity in endothelial cells. HUVEC, WT-HEK and HEK-eNOS cells were treated with TERPY at different times (0 to 60 minutes). Were analyzed by western blotting the TERPY`s effect on eNOS monomer, dimer and phosphorylation and on monomer and oligomer of caveolin-1. It was also evaluated the effect of TERPY in the interaction between eNOS/Cav-1 through co-immunoprecipitation. Alterations induced by TERPY on reactive oxygen species and peroxynitrite concentrations in endothelial cells were measured by using DHE probe and biosensor 7-CBA, respectively. Nitric oxide fluorescence was assessed by DAF-FM probe and Cooper sensor. TERPY promoted eNOS uncoupling and eNOS dysfunction, which is BH4-dependent. Caveolin-1 oligomers destabilization was induced by TERPY. Consequently, TERPY reduced eNOS/Cav-1 interaction and promoted eNOS activation. Our results show that eNOS activity can be regulated in two different ways by TERPY, leading to eNOS uncoupling and leading to eNOS phosphorylation, promoting a strategy for eNOS regulation. Chemical or biological molecules as TERPY that regulates eNOS activity and increase NO production and bioavailability are potential therapeutic drugs for the treatment of vascular diseases associated with hypertension(AU)

Intensive Long Distance Running as a Possible Cause of Multiple Splanchnic Arterial Aneurysms: A Case Report

This is a case report that suggests the possible association between multiple splanchnic arterial aneurysms and long-distance running. The clinical features of one patient admitted at Chungbuk National University Hospital for treatment of multiple splanchnic arterial aneurysms were reviewed. A 54-year-old man had a recurrent, intermittent and epigastric pain for 2 months. There was no abnormality in gastroscopy and colonoscopy. An abdominal computed tomography angiography documented calcified superior mesenteric artery (SMA) and splenic artery aneurysms. The patient had a history of recreational long-distance running for over 10 years. His average running time per week was more than 10 hours. There was no evidence of systemic arteritis, connective tissue disorder or infectious process that may have caused the aneurysms. He did not take any drugs. The SMA aneurysm was opened, and the aneurysmal segment of SMA was replaced with a vein graft. The splenic aneurysm was observed. The patient recovered without any sequelae.

Multiple visceral artery aneurysms managed by Yasargil aneurysm clips

Here, we present the case of a 37-year-old woman with multiple visceral artery aneurysms in the pancreaticoduodenal, inferior pancreatic and splenic arteries associated with celiac trunk stenosis. An aneurysmectomy and end-to-end anastomosis was performed for two adjacent aneurysms, while clipping with intracranial aneurysm clips were performed for the other three aneurysms. During 36-month follow-up, no recurrence or newly developed lesions were noted, and the celiac artery had been reconstituted spontaneously. We believe that using intracranial aneurysm clips in the treatment of visceral artery aneurysms is feasible and safe and can be considered when endovascular procedures are unlikely to be successful.

Effects of different concentrations of dexmedetomidine on BKCa channels in rat mesenteric arterial smooth muscle cells / 中华麻醉学杂志

Objective To evaluate the effects of different concentrations of dexmedetomidine on large-con-ductance Ca2+-activated K+ (BKca) channels in the rat mesenteric arterial smooth muscle (MASM) cells.Methods Sprague-Dawley rats of both sexes,weighing 180-220 g,were used in this study.Single MASM cell was freshly isolated from mesenteric arteries in two steps.Ten cells were chosen and studied.When holding potential was 40 mV and the concentration of free calcium ions was 10-7 mol/L,inside-out patch-clamp technique was used to record the single BKCa channel current before and after application of different concentrations of dexmedetomidine (0,10-9,10-8,10-7,10-6,10-5 mol/L).Total open probability (NPo),amplitude (Am),mean open time (To) and mean close time (To) of single BKca channel were observed and recorded.Results Compared with the baseline value,dexmedetomidine 10-7,10-6 and 10-5 mol/L increased NPo in a concentration-dependent man-ner,and dexmedetomidine 10-9,10-8,10-7,10-6,10-5mol/L shortened Tc (P ＜0.05 or 0.01).Compared with the value obtained when the concentration of dexmedetomidine was 10-9 mol/L,Tc was significantly shortened when the concentration of dexmedetomidine was 10-8 mol/L (P ＜ 0.05),and no significant change was found in Am and To obtained when different concentrations of dexmedetomidine were applied (P ＞ 0.05).Conclusion Dexmedetomidine 10-7,10-6 and 10-5 mol/L activate BKca channels in rat MASM cells in a concentration-depen-dent manner,which is one of the mechanisms of decrease in blood pressure by dexmedetomidine.

Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients

The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: Km (r = 0.612, P = 0.034) and Vmax (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: Km (r = -0.625, P = 0.029) and Vmax (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

Gender difference and change of alpha1-adrenoceptors in the distal mesenteric arteries of streptozotocin-induced diabetic rats / 대한마취과학회지

BACKGROUND: The purpose of this study was to evaluate the gender-related changes in the function and distribution of alpha1-adrenoceptors in the distal mesenteric artery of streptozotocin (STZ)-induced diabetic rats at the level of alpha1-adrenoceptor subtypes. METHODS: Diabetes was induced by intravenous injection of STZ in a dose of 60 mg/kg through the tail vein in 8 week-old male or female Sprague-Dawley rats (n = 13/group). Age-matched normal rats (n = 15) were used as a control group. Four weeks after STZ injection, the change in mean arterial pressure caused by a 45degrees tilting was recorded. The alpha1-adrenoceptor subtypes mediating contractions of the distal mesenteric artery were investigated using the agonist, phenylephrine as well as subtype-selective antagonists including prazocin, 5-methylurapidil, and BMY 7378. The expression of alpha1-adrenoceptor subtypes of each artery was examined by immunofluorescence staining and western blotting using subtype selective antibodies. RESULTS: Compared with normal male rats, the contractile response to phenylephrine was decreased in the distal mesenteric artery in normal female rats. Moreover, a decrease in contractile force was observed in STZ-induced diabetic rats compared with age-matched controls. Western blotting revealed that there was the difference between normal male and female rats in manifestation of the alpha1D-adrenoceptor. In STZ-induced male and female diabetic rats, all alpha1-adrenoceptor subtypes were decreased in distal mesenteric arteries, compared with normal rats. CONCLUSIONS: There was the gender-related functional difference of alpha1-adrenoceptors in normal rats. In both male and female rats, diabetes decreased the contractile response in mesenteric arteries, which might be caused by the overall change in alpha1-adrenoceptor.

Clinical Effectiveness of Percutaneous Angioplasty for Acute and Chronic Mesenteric Ischemia: A Six Case Series / 대한소화기학회지

Intestinal ischemia is divided into three categories, namely, acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), and colonic ischemia. AMI can result from arterial or venous thrombi, emboli, and vasoconstriction secondary to low-flow states. It is an urgent condition which can result in high mortality rate. The predominant causative factor of CMI is stenosis or occlusion of the mesenteric arterial circulation, and it is characterized by postprandial abdominal pain and weight loss. Surgery is the treatment of choice for intestinal ischemia. However, it has been recently reported that percutaneous transluminal angioplasty with stent placement and/or thrombolysis is an effective therapy in various types of mesenteric ischemia. We report six cases of mesenteric ischemia which were successfully treated by percutaneous angioplasty, and review the literature from South Korea.

Clinical Effectiveness of Percutaneous Angioplasty for Acute and Chronic Mesenteric Ischemia: A Six Case Series / 대한소화기학회지

Intestinal ischemia is divided into three categories, namely, acute mesenteric ischemia (AMI), chronic mesenteric ischemia (CMI), and colonic ischemia. AMI can result from arterial or venous thrombi, emboli, and vasoconstriction secondary to low-flow states. It is an urgent condition which can result in high mortality rate. The predominant causative factor of CMI is stenosis or occlusion of the mesenteric arterial circulation, and it is characterized by postprandial abdominal pain and weight loss. Surgery is the treatment of choice for intestinal ischemia. However, it has been recently reported that percutaneous transluminal angioplasty with stent placement and/or thrombolysis is an effective therapy in various types of mesenteric ischemia. We report six cases of mesenteric ischemia which were successfully treated by percutaneous angioplasty, and review the literature from South Korea.

Estudo das anastomoses entre os territórios de irrigação das artérias mesentéricas cranial e caudal (arcada paracólica) após ligadura das artérias mesentérica caudal e retais médias e inferiores combinada com colostomia perineal no cão / Study of the anastomoses between the territories of irrigation of the cranial and caudal mesenteric arteries (paracholic arch) after ligation of the caudal mesenteric arteries and the middle and lower rectal combined with perineal colostomy in the dog

Objetivo: investigar experimentalmente o suprimento arterial do colo descendente e reto, após ligadura da artéria mesentérica caudal, pela análise da viabilidade da arcada paracólica suprida pela persistência da irrigação do colo descendente. Métodos: foram estudados 30 animais separados em três grupos para observação pós-operatória de 24, 48 e 72 horas. Realizaram-se laparotomia, ligadura da artéria mesentérica caudal e dos vasos retais médios, ligadura do pedículo vascular retal inferior, amputação do reto e posterior colostomia perineal. Foi realizada relaparotomia após o período de observação, com identificação da mesma região. Os cães foram, então, mortos, sendo retirados três pequenos segmentos: um a 10 cm e dois a 10 cm acima e abaixo do linfonodo mesentérico caudal, respectivamente. Resultados: no grupo de animais observados com 72 horas de pós-operatório, abaixo do linfonodo, houve viabilidade estatisticamente significativa, tendo ocorrido necrose estatisticamente significativa nos grupos de 24 e 48 horas. Conclusão: a viabilidade do cólon e do reto cranial depende de anastomose entre os territórios da mesentérica cranial e caudal, mas essa comunicação não está presente em todos os animais.

Objective: experimentally investigate the arterial supply of the descending colon and rectum after ligation of the caudal mesenteric artery, by examining the viability of the paracolic arcade supplied by the persistent irrigation of the descending colon. Methods: 30 animals separated into three groups for 24, 48 and 72 hours posoperatory observation were under study. Laparotomy, ligation of the caudal mesenteric artery and middle rectal vessels, ligation of the inferior rectal vascular pedicle, amputation of lhe rectum and posterior perineal colostomy were performed. Then the dogs were killed, and three small segments were removed: one at 10 cm and two others at 10 cm above and below the caudal mesenteric lymph nodes, respectively. Results: in the group of animals observed with 72 hours posoperatory, there was statistically significant viability below the limph node,with statistically significant necrosis in the 24 and 48 hour groups. Conclusions: the viability of colon and rectal cranial depends on the anastomosis between the territories of the cranial and caudal mesentric, but this communication is not found in all the animals.

Effects of remifentanil on large-conductance Ca2+ -activated potassium channels in human mesenteric arterial smooth muscle cells / 中华麻醉学杂志

Objective To investigate the effects of remifentanil on large-conductance Ca2+ -activated potassium channel (BKCa) in human mesenteric arterial smooth muscle cells (MASMCs) and the mechanism of the vasorelaxant effect of remifentanil. Methods Human MASMCs were obtained freshly by the method of enzymolysis. BKCa current (IBKCa) was recorded by the whole-cell patch clamp technique. The changes in IBKC. produced by different concentrations of remifentanil (1.2, 4.8, 19.4, 77.4 and 310.0 nmol/L) with the holding potential of + 80 mV were observed. BKCa activation rate was calculated. Results Remifentanil significantly increased IBKCa,moved Ⅰ-Ⅴ curve upward and had no effect on the threshold of activation for IBKCa . With the increase in the concentration of remifentanil, BKCa activation rate increased gradually (P ＜ 0.01), and it remained stable when the concentration reached 19.4 nmol/L. There was no significant difference in the peak time of IBKCa after different concentrations of remifentanil were given (P ＞ 0.05). Logarithmic curve was found to suit the relationship between the concentration of remifentanil and BKCa activation rate and the IC50 concentration was (118 ± 7) nmol/L. Conclusion Remifentanil results in vasorelaxation by activating BKCa in MASMCs in a concentration-dependent manner.

A key role for Na+/K+-ATPase in the endothelium-dependent oscillatory activity of mouse small mesenteric arteries

Oscillatory contractile activity is an inherent property of blood vessels. Various cellular mechanisms have been proposed to contribute to oscillatory activity. Mouse small mesenteric arteries display a unique low frequency contractile oscillatory activity (1 cycle every 10-12 min) upon phenylephrine stimulation. Our objective was to identify mechanisms involved in this peculiar oscillatory activity. First-order mesenteric arteries were mounted in tissue baths for isometric force measurement. The oscillatory activity was observed only in vessels with endothelium, but it was not blocked by L-NAME (100 µM) or indomethacin (10 µM), ruling out the participation of nitric oxide and prostacyclin, respectively, in this phenomenon. Oscillatory activity was not observed in vessels contracted with K+ (90 mM) or after stimulation with phenylephrine plus 10 mM K+. Ouabain (1 to 10 µM, an Na+/K+-ATPase inhibitor), but not K+ channel antagonists [tetraethylammonium (100 µM, a nonselective K+ channel blocker), Tram-34 (10 µM, blocker of intermediate conductance K+ channels) or UCL-1684 (0.1 µM, a small conductance K+ channel blocker)], inhibited the oscillatory activity. The contractile activity was also abolished when experiments were performed at 20°C or in K+-free medium. Taken together, these results demonstrate that Na+/K+-ATPase is a potential source of these oscillations. The presence of α-1 and α-2 Na+/K+-ATPase isoforms was confirmed in murine mesenteric arteries by Western blot. Chronic infusion of mice with ouabain did not abolish oscillatory contraction, but up-regulated vascular Na+/K+-ATPase expression and increased blood pressure. Together, these observations suggest that the Na+/K+ pump plays a major role in the oscillatory activity of murine small mesenteric arteries.