Luminal Delivery of Pectin-Modified Oxygen Microbubbles Mitigates Rodent Experimental Intestinal Ischemia.

INTRODUCTION: Ischemic gut injury is common in the intensive care unit, impairs gut barrier function, and contributes to multiorgan dysfunction. One novel intervention to mitigate ischemic gut injury is the direct luminal delivery of oxygen microbubbles (OMB). Formulations of OMB can be modified to control the rate of oxygen delivery. This project examined whether luminal delivery of pectin-modified OMB (OMBp5) can reduce ischemic gut injury in a rodent model. METHODS: The OMBp5 formulation was adapted to improve delivery of oxygen along the length of small intestine. Adult Sprague-Dawley rats (n = 24) were randomly allocated to three groups: sham-surgery (SS), intestinal ischemia (II), and intestinal ischemia plus luminal delivery of OMBp5 (II + O). Ischemia-reperfusion injury was induced by superior mesenteric artery occlusion for 45 min followed by reperfusion for 30 min. Outcome data included macroscopic score of mucosal injury, the histological score of gut injury, and plasma biomarkers of intestinal injury. RESULTS: Macroscopic, microscopic data, and intestinal injury biomarker results demonstrated minimal intestinal damage in the SS group and constant damage in the II group. II + O group had a significantly improved macroscopic score throughout the gut mucosa (P = 0.04) than the II. The mean histological score of gut injury for the II + O group was significantly improved on the II group (P ≤ 0.01) in the proximal intestine only, within 30 cm of delivery. No differences were observed in plasma biomarkers of intestinal injury following OMBp5 treatment. CONCLUSIONS: This proof-of-concept study has demonstrated that luminal OMBp5 decreases ischemic injury to the proximal small intestine. There is a need to improve oxygen delivery over the full length of the intestine. These findings support further studies with clinically relevant end points, such as systemic inflammation and vital organ dysfunction.

Iodine density mapping for the diagnosis of acute bowel ischemia using fast kV-switching dual-energy CT.

PURPOSE: To evaluate the diagnostic capabilities of a supplementary color ramped iodine density map compared to virtual monoenergetic images (VMIs) at 74 keV in the diagnosis of acute bowel ischemia (ABI). METHODS: Data for this study were prospectively gathered and retrospectively evaluated. Patients referred to the Department of Diagnostic Radiology between October 2020 and August 2022 on the suspicion of ABI and underwent surgery < 12 h following fast kV-switching venous phase abdominal dual-energy CT (DECT) were consecutively included. Images were evaluated by two board-certified radiologists and two radiology residents. First round included only 74 keV VMIs resembling conventional 120 kVp images, and the second round included a supplementary iodine density map. Readers were asked to register presence of ABI as well as their confidence in their diagnosis based on a 5-point Likert scale. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each observer with the surgical findings as the gold-standard. McNemar's and Wilcoxon signed-rank test were used to compare registrations and diagnostic confidence across assessment rounds. RESULTS: A total of 29 patients resulting in 31 DECT scans were included. Fourteen cases of ischemic/necrotic bowel were reported following surgery. Sensitivity and NPV were decreased with the use of supplementary iodine map images compared to 120 kVp-like images without supplementary iodine map images for three of four observers (round 1 range: 71.4-92.9% and 78.0-94.8%; round 2 range: 57.1-78.6% and 70.1-83.3%, respectively), while specificity and PPV were increased for three of four observers (round 1 range: 64.7-94.1% and 67.4-93.1%; round 2 range: 88.2-94.1% and 73.8-91.1%, respectively). However, no significant difference in ABI diagnosis or diagnostic confidence was found (p-value range: 0.07-1.00 and 0.23-0.58, respectively). CONCLUSION: No significant difference for the diagnosis of ABI was found using supplementary iodine mapping. Our study may suggest a trend of increased specificity and decreased sensitivity, hence, the use of supplementary iodine mapping should be carefully considered.

Increased blood lactate during enteral nutrition in the critically ill: associations and treatment options.

PURPOSE OF REVIEW: To evaluate the significance of blood lactate increase during enteral nutrition in the critically ill, and to propose diagnostic and therapeutic strategies. RECENT FINDINGS: Acute mesenteric ischemia occurs in approximately 1% of critically ill patients treated with catecholamine. Recent literature suggests that enteral nutrition is a risk factor of acute mesenteric ischemia, in particular in case of low cardiac output, by a mechanism of nonocclusive mesenteric ischemia. The association of clinical, biological, and computed tomography imaging might help to evaluate the reversibility of acute mesenteric ischemia. SUMMARY: As enteral nutrition induces an increased metabolic work of the gut, the inadequation between oxygen delivery and demand exposes the gut to a phenomenon of nonocclusive mesenteric ischemia. Before initiation of enteral nutrition,, and before each increase of the enteral nutrition dose, the risk factors of nonocclusive mesenteric ischemia should be searched in order to prevent it. While under enteral nutrition, increased lactate concentration while receiving enteral nutrition requires the urgent search for nonocclusive mesenteric ischemia, and the adaptation of enteral nutrition (reduction, stop, and/or switch to parenteral nutrition or tolerate early nutrient restriction). Early signs of nonocclusive mesenteric ischemia should be searched in order to allow for a rapid diagnosis, before development of irreversible transmural necrosis. After the diagnosis of acute mesenteric ischemia, improving the balance between oxygen demand and delivery to the gut, evaluating the reversibility of the gut ischemia, and performing urgent resection in case of irreversible transmural necrosis should be the main objectives. After the resolution of acute mesenteric ischemia, the benefit risk analysis of enteral nutrition reintroduction should be evaluated.

Oral administration of n-3 fatty acids positively affect the mucosal lesions after experimental ischemic enteritis in the rat.

AIM: The purpose of the study was to evaluate the effect of oral administration of n-3 polyunsaturated fatty acids in experimental ischemic enteritis in rats. METHODS: Forty Wistar rats were submitted to control narrowing of the superior mesenteric artery and were divided in two groups: N3 polyunsaturated fatty acids, which received a high-molecular polymer solution of artificial total enteral nutrition enriched with n-3 fatty acids and CONTROL which received a high-molecular polymer solution of artificial total enteral nutrition. RESULTS: Reduction of the animals' body weight was observed in both groups, but there was no difference between the two groups. Regarding the level of cytokines interleukin (IL)-1b, IL-6, and tumor necrosis factor a (TNF-a) there was no statistically significant difference between the two groups. Ischemic lesions to the small bowel mucosa were observed in both groups. A statistically significant difference in the extent of intestinal lesions was observed between the two groups with the animals that received enteral nutrition enriched with n-3 fatty acid developing fewer lesions. CONCLUSION: Enteral nutrition enriched with n-3 polyunsaturated fatty acids reduces the mucosal lesions caused by mesenteric ischemia compared to standard enteral nutrition, by modifying the local, but not the systemic, immune, and inflammatory response.

OBJETIVO: El propósito del estudio fue evaluar el efecto de la administración oral de ácidos grasos poliinsaturados n-3 en enteritis isquémica experimental en ratas. MÉTODOS: 40 ratas Wistar fueron sometidas a un estrechamiento controlado de la arteria mesentérica superior y se dividieron en dos grupos: N3PUFA, que recibieron una solución de polímero de alto peso molecular de nutrición enteral total artificial enriquecida con ácidos grasos n-3 y CONTROL que recibió un alto -Solución de polímero molecular de nutrición enteral total artificial. RESULTADOS: Se observó una reducción del peso corporal de los animales en ambos grupos, pero no hubo diferencias entre los dos grupos. Con respecto al nivel de citocinas IL-1b, IL-6 y TNF-a, no hubo diferencia estadísticamente significativa entre los dos grupos. Se observaron lesiones isquémicas de la mucosa del intestino delgado en ambos grupos. Se observó una diferencia estadísticamente significativa en la extensión de las lesiones intestinales entre los dos grupos y los animales que recibieron nutrición enteral enriquecida con ácido graso n-3 desarrollaron menos lesiones. CONCLUSIÓN: La nutrición enteral enriquecida con ácidos grasos poliinsaturados n-3 reduce las lesiones mucosas causadas por isquemia mesentérica en comparación con la nutrición enteral estándar, al modificar la respuesta local, pero no sistémica, inmunitaria e inflamatoria.

The effects on bacterial translocation and tissue damage of selenium treatment in an experimental intestina ischaemia-reperfusion model.

BACKGROUND: The free oxygen radicals formed with reperfusion following intestinal ischaemia are extremely toxic for the cells. Glutathione peroxidase, an important enzyme that prevents the formation of reactive oxygen species, requires selenium as a co-factor. This study aims to demonstrate the effects of selenium administration on reducing ischaemia-reperfusion damage. METHODS: In this study, 28 male Wistar rats were separated into four groups. To Groups 3 and 4, sodium selenite at the dose of 10 µg/kg/day was administered intraperitoneally for five days. In Groups 1 and 3, laparotomy was applied, and in Groups 2 and 4, following laparotomy, ischaemia was created by clamping the superior mesenteric artery for 45 mins, then reperfusion was provided for 90 mins. Blood, liver and ileum samples were taken from all the animals for examination of malondialdehyde. For examination of bacterial translocation, liver, spleen and mesenteric lymph node tissue samples were taken. A sample taken from the ileum was examined histopathologically. RESULTS: There was determined to be significantly more bacterial translocation in the mesenteric lymph nodes of the ischaemia-reperfusion group (p<0.05). In the histopathological evaluation, the score in the ischaemia-reperfusion group was significantly higher than the scores in the other groups (p<0.05). Elevated serum, liver and ileum malondialdehyde levels in the ischaemia-reperfusion group were significantly higher than those in the other groups (p<0.05). CONCLUSION: Selenium was seen to have decreased serum and tissue malondialdehyde levels and increased the histopathological damage developing in the intestines with ischaemia-reperfusion and thereby increased bacterial translocation.

Protective effects of Ficus carica seed oil on ischemia and reperfusion injury in a rat model of acute mesenteric ischemia.

BACKGROUND: The increase in free oxygen radicals and proinflammatory cytokines in the ischemia-reperfusion injury caused by acute mesenteric ischemia are the key responsibilities of intestinal histopathological alterations. It has been reported that Ficus carica and its various parts contain antioxidant and anti-inflammatory compounds recently. Thus, in the present study, we aimed to investigate how Ficus carica seed oil affects intestinal ischemia-reperfusion injury in a rat model. METHODS: In this study, 50 male Wistar albino rats were randomly divided into five equal groups. Negative control (NC), sham-operated (Sham), ischemia and reperfusion (IR), 3 ml/kg/day Ficus carica seed oil (FC3), 6 ml/kg/day Ficus carica seed oil (FC6). IR, FC3 and FC6 groups underwent ischemia and reperfusion procedure for 45+120 min. Only abdominal midline laparotomy was performed in the Sham group for 165 minutes. RESULTS: Tissue levels of TNFα and IL-1ß, which were proinflammatory cytokines, were significantly reduced in the FC6 group than the IR group (p<0.05). In FC3 and FC6 groups, the tissue MPO and MDA enzyme levels were significantly lower than the IR group, but there was a significantly greater decrease in the FC6 group than the FC3 group (p<0.05). SOD and CAT enzymes and reduced glutathione levels of FC3 and FC6 groups were significantly lower than IR group (p<0.05); however, there was no statistically significant difference between the FC3 and FC6 groups. FC3 and FC6 groups were histopathologically graded statistically lower than the IR group, and the FC6 group showed a significant decrease than the FC3 group (p<0.05). CONCLUSION: Oral administration of fig seed oil may reverse biochemical and histopathological findings resulting from ischemia-reperfusion injury in an experimental model of acute mesenteric ischemia in rats, probably because of its antioxidant and anti-inflammatory compounds.

Early risk stratification of patients with suspected chronic mesenteric ischaemia using a symptom and mesenteric artery calcium score based score chart.

BACKGROUND: The mesenteric artery calcium score (MACS) identifies patients with possible chronic mesenteric ischaemia (CMI) using standard computed tomography (CT) imaging. The MACS does not necessitate a dedicated computed tomography angiography (CTA) which is required for evaluation of mesenteric artery patency. This study aimed to test the use of a symptom and MACS based score chart to facilitate the selection of patients with a low probability of CMI, in whom further diagnostic workup can be omitted, and to validate the CTA-based score chart proposed by van Dijk et al. which guides treatment decisions in patients with suspected CMI. METHODS: This retrospective study included consecutive patients with suspected CMI. The Agatston definition was used to calculate the MACS. Multivariable logistic regression analysis was used to create a MACS score chart, which was applied in all patients to determine its discriminative ability. The score chart by van Dijk et al. was validated in this independent external patient series. RESULTS: Hundred-ninety-two patients were included, of whom 49 had CMI. The MACS score chart composed of the variables weight loss, postprandial abdominal pain, history of cardiovascular disease, and MACS, showed an excellent discriminative ability (area under the curve [AUC] 0.87). CMI risks were 2.1% in the low-risk group (0-4 points) and 39.1% in the increased risk group (5-10 points); sensitivity (97.8%) and negative predictive value (NPV; 97.9%) were high. The CTA-based score chart by van Dijk et al. showed an excellent discriminative ability (AUC 0.89). CONCLUSION: The MACS score chart shows promise for early risk stratification of patients with suspected CMI based on a near-perfect NPV. It is complementary to the CTA-based score chart by van Dijk et al., which showed excellent external validity and is well suited to guide subsequent (invasive) treatment decisions in patients with suspected CMI.

Fully automatic d-lactate assay using a modified commercially available method.

Intestinal infarction is the fast-evolving endpoint of impaired blood perfusion to an intestinal segment which may have fatal outcome. Early diagnosis and treatment within 6 h reduce mortality. Currently, d-lactate is a promising biomarker, however, not available in the acute clinical setting. The aim of this study is implementation of d-lactate analysis in a routine clinical setting. We used a spectrophotometric method, based on enzymatic oxidation of d-lactate by d-lactate dehydrogenase (D-LDH) coupled to the reduction of nicotinamide-adenine dinucleotide (NAD+). The amount of NADH formed in this reaction is equivalent to d-lactate. The primary concern in this method is interfering NADH formed by oxidation of l-lactate by l-lactate dehydrogenase (L-LDH). A commercially available kit for d-lactate measurement was implemented on our existing automated routine laboratory equipment including pH-inactivation of L-LDH. Our setup fulfilled clinical quality goals. We were able to measure d-lactate with an acceptable performance of the analysis and a short turn-around time. The method can be used to distinguish between the expected cut-off for intestinal ischemia around 0.3 mM and the upper reference limit of 0.05 mM. With a turnaround time of just 9 min, the analysis has potential as a readily available detection of circulating d-lactate for early diagnosis of intestinal ischemia.

Outcomes of long-term anticoagulant treatment for the secondary prophylaxis of splanchnic venous thrombosis.

BACKGROUND: Splanchnic vein thrombosis (SVT) is an uncommon but potentially life-threatening disease usually related to different underlying clinical conditions. The risk of SVT recurrences is high over time in patients with an underlying permanent prothrombotic condition. Vitamin K antagonists (VKA) represent the mainstay of treatment for SVT. Data about the efficacy and safety of direct oral anticoagulants (DOACs) are reported in the literature for the treatment of acute SVT, but less is known about their application for the secondary prophylaxis of venous thromboembolism (VTE). The aim of this study was to assess the efficacy and safety of long-term DOACs therapy in patients at high-risk of thrombosis, compared to VKA. METHODS: This is a retrospective single-centre study including 70 patients with SVT on long-term anticoagulant treatment with VKA followed-up at our Units between January 2017 and December 2019. All the patients were at high thrombotic risk defined as the presence of a permanent prothrombotic condition requiring long-term anticoagulation. During follow-up, 28 patients were shifted to DOACs and their clinical outcomes were compared to those of the patients who continued VKA therapy. All the arterial and venous thrombotic events of the splanchnic and extra-splanchnic districts as well as the haemorrhagic adverse events occurring during follow-up were recorded. RESULTS: Of the seventy patients enrolled in the study, 36 patients (51.4%) had a single-segment involvement thrombosis (28.5% of portal vein, 7.1% of superior mesenteric vein, 4.3% of splenic vein, 11.5% of hepatic veins) and 34 patients (48.6%) had multi-segment involvement at the time of diagnosis. 42 patients (60%) continued VKA therapy and 28 (40%) were switched to DOACs. Median follow-up was 6 years (range 2-8) during VKA and 1.9 years (range 1-5.2) during DOACs. The incidence of thrombotic events was similar between patients on VKA and those on DOACs. Patients on VKA developed deep vein thrombosis (DVT), and of the patients on DOACs 1 developed NSTEMI and 1 DVT. No major haemorrhagic events occurred. Minor bleedings occurred in 26% of patients on VKA and in none of the DOACs patients (P: 0.09). CONCLUSIONS: Our results highlight that DOACs could represent an effective and safe alternative to the VKA for secondary prophylaxis in SVT patients at high risk of thrombosis.

Prophylaxis with rivaroxaban after laparoscopic sleeve gastrectomy could reduce the frequency of portomesenteric venous thrombosis.

INTRODUCTION: Portal and mesenteric venous thrombosis is a rare but potentially serious complication after laparoscopic sleeve gastrectomy. There are no consistent studies that prove the safety and effectiveness of oral anticoagulant thromboprophylaxis with rivaroxaban after laparoscopic sleeve gastrectomy. The objective was to evaluate the effect of rivaroxaban on the frequency of portal and mesenteric venous thrombosis and its safety profile after laparoscopic sleeve gastrectomy. MATERIALS AND METHODS: This retrospective analysis of prospectively collected data includes all laparoscopic sleeve gastrectomies performed by a single surgeon at Pontificia Universidad Católica de Chile Hospital between January 2009 and June 2019. All patients received low molecular weight heparin thromboprophylaxis during the whole hospital stay. Between July 2012 and June 2019, patients received additional post-discharge thromboprophylaxis with rivaroxaban. Patient demographics, impaired renal, post-surgical portal and mesenteric venous thrombosis, and bleeding episodes were registered. RESULTS: A total of 516 patients were identified; 95 patients were excluded. Results for 421 patients were analysed: 198 received only intrahospital thromboprophylaxis (group 1) and 223 received additional post-discharge thromboprophylaxis with rivaroxaban (group 2). There was no statistically significant difference between the two groups concerning age, sex and body mass index. In group 1, four cases of portal and mesenteric venous thrombosis were registered and no cases were reported in group 2 (p < 0.05). All cases occurred before 30 days after surgery. No bleeding episodes and no adverse reactions were detected in group 2. CONCLUSIONS: Thromboprophylaxis during the whole hospital stay (two to three days), followed by rivaroxaban 10mg once daily for 10 days after discharge (completing in total 13-14 days of prophylaxis), could reduce cases of post-surgical portal and mesenteric venous thrombosis without an increase in bleeding complications.

European guidelines on chronic mesenteric ischaemia - joint United European Gastroenterology, European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Gastrointestinal and Abdominal Radiology, Netherlands Association of Hepatogastroenterologists, Hellenic Society of Gastroenterology, Cardiovascular and Interventional Radiological Society of Europe, and Dutch Mesenteric Ischemia Study group clinical guidelines on the diagnosis and treatment of patients with chronic mesenteric ischaemia.

Chronic mesenteric ischaemia is a severe and incapacitating disease, causing complaints of post-prandial pain, fear of eating and weight loss. Even though chronic mesenteric ischaemia may progress to acute mesenteric ischaemia, chronic mesenteric ischaemia remains an underappreciated and undertreated disease entity. Probable explanations are the lack of knowledge and awareness among physicians and the lack of a gold standard diagnostic test. The underappreciation of this disease results in diagnostic delays, underdiagnosis and undertreating of patients with chronic mesenteric ischaemia, potentially resulting in fatal acute mesenteric ischaemia. This guideline provides a comprehensive overview and repository of the current evidence and multidisciplinary expert agreement on pertinent issues regarding diagnosis and treatment, and provides guidance in the multidisciplinary field of chronic mesenteric ischaemia.

Protective effect of hyperbaric oxygen treatment on rat intestinal mucosa after mesenteric ischaemia and reperfusion.

INTRODUCTION: Mesenteric ischaemia results from a lack of adequate blood flow to and oxygenation of the mesentery and intestines. The aim of the present study was to evaluate the effect of hyperbaric oxygen treatment (HBOT) on the healing process in intestinal mucosa of rats undergoing mesenteric ischaemia and reperfusion. METHODS: Thirty-two Wistar-Albino rats were divided into four groups of eight: 1) ischaemia/reperfusion (I/R); 2) sham operation; 3) I/R+HBOT started 6 hours after reperfusion; 4) I/R+HBOT started 12 hours after reperfusion. In the I/R groups, a vascular clamp was placed across the superior mesenteric artery to occlude arterial circulation for 60 minutes, followed by reperfusion. A dose of HBOT consisted of 100% oxygen breathing for 90 minutes at 2.5 atmospheres absolute pressure. Thirteen doses of HBOT were administered after ischaemia. The rats were sacrificed on the eighth day, and their intestinal tissues were harvested for histopathologic analysis. The tissue levels of catalase, malondialdehyde, and glutathione were determined. RESULTS: The histopathological scores (HSCORE) were consistent with macroscopic examinations. The scores were significantly higher (worse) in Group 1 compared to Group 2, Group 3, and Group 4 (for all comparisons, P < 0.05). Group 4's HSCORE was significantly higher than those of Group 2 and Group 3 (for both comparisons P < 0.05). Group 3's HSCOREs were only marginally higher than Group 2. Group 3 exhibited higher glutathione levels than Group 1 (P < 0.05). There were no significant differences across the groups with respect to malondialdehyde and catalase levels. CONCLUSION: A beneficial effect of HBOT was observed on oxidative stress and inflammation in acute mesenteric ischaemia-reperfusion.

Dobutamine Versus Vasopressin After Mesenteric Ischemia.

BACKGROUND: Gastrointestinal blood flow may be compromised during and after vasopressor support. Endothelin expression may lead to microcirculatory dysfunction. The aim of this study was to analyze the effect of vasopressin and dobutamine after mesenteric ischemia on the gastrointestinal mucosal microcirculation, endothelin expression, and morphologic injury. MATERIALS AND METHODS: Pigs were studied in four groups (six pigs in each group): 1, sham; 2-4 ischemia (1 h superior mesenteric artery occlusion with 30 min reperfusion and 30 min of vehicle [2], dobutamine [3], or vasopressin [4] administration, followed by 30-min break and thiopental-induced hypotension [3, 4]). Blood flow of the gastric, jejunal, and rectosigmoidal mucosa was measured. At the end of the experiment, the mucosal expression of endothelin-1 (ET-1) and its receptor subtypes A (ETA) and B were determined by polymerase chain reaction. Mucosal injury, apoptotic cell death, and leukocytic infiltration were determined by histology and immunohistochemical analysis of cleaved caspase-3 and myeloperoxidase. RESULTS: Mesenteric ischemia increased jejunal mucosal ET-1 gene expression, arterial ET-1, intestinal fatty acid binding protein, and jejunal mucosal injury compared with sham. Dobutamine increased arteriovenous shunting at the cost of the jejunal mucosal blood perfusion. This was associated with an increased expression of ET-1 and ETA and mucosal leukocytic infiltration. In contrast, vasopressin increased postischemic capillary density and tissue blood flow. This was associated with a lower ET-1 gene expression. Vasopressin did not induce jejunal mucosal leukocytic infiltration. CONCLUSIONS: Vasopressin reduces mesenteric ischemia-associated alterations of the microcirculation and tissue integrity, whereas dobutamine does not.

Cold-inducible RNA-binding protein-derived peptide C23 attenuates inflammation and tissue injury in a murine model of intestinal ischemia-reperfusion.

BACKGROUND: Cold-inducible RNA-binding protein is a novel damage-associated molecular pattern that causes inflammation. C23, a short peptide derived from cold-inducible RNA-binding protein, has been found to have efficacy in blocking cold-inducible RNA-binding protein's activity. We hypothesized that C23 reduces inflammation and tissue injury induced by intestinal ischemia-reperfusion. METHODS: Male C57BL/6 mice were subjected to 60 minutes of intestinal ischemia by clamping the superior mesenteric artery. Immediately after reperfusion, either normal saline (vehicle) or C23 peptide (8 mg/kg body weight) was injected intraperitoneally. Four hours after reperfusion, blood, intestinal, and lung tissues were collected for analysis of inflammatory and tissue injury parameters. RESULTS: Cold-inducible RNA-binding protein levels in the intestinal tissues were significantly increased following intestinal ischemia-reperfusion. Histologic examination of the intestine revealed a significant reduction in injury score in the C23 group by 48% as compared with the vehicles after intestinal ischemia-reperfusion. The serum levels of lactate dehydrogenase and aspartate aminotransferase were increased in animals that underwent vehicle-treated intestinal ischemia-reperfusion, whereas C23-treated animals exhibited significant reductions by 48% and 53%, respectively. The serum and intestinal tissue levels of tumor necrosis factor α were elevated in vehicle-treated intestinal ischemia-reperfusion mice but decreased by 72% and 69%, respectively, in C23-treated mice. Interleukin-6 mRNA levels in the lungs were reduced by 86% in the C23-treated group in comparison to the vehicle-treated group after intestinal ischemia-reperfusion. Expression of macrophage inflammatory protein 2 and level of myeloperoxidase activity in the lungs were dramatically increased after intestinal ischemia-reperfusion and significantly reduced by 91% and 25%, respectively, in the C23-treated group. CONCLUSION: C23 has potential to be developed into a possible therapy for reperfusion injury after mesenteric ischemia and reperfusion.

Nicotinamide riboside has protective effects in a rat model of mesenteric ischaemia-reperfusion.

Acute mesenteric ischaemia is a syndrome caused by inadequate blood flow through the mesenteric vessels, resulting in ischaemia and eventual gangrene of the bowel wall. Although relatively rare, it is a potentially life-threatening condition. The maintenance of haemodynamic stability, along with adequate oxygen saturation, and the correction of any electrolyte imbalance, are of the utmost importance. However, nicotinamide adenine dinucleotide (NAD) biosynthesis modulation by precursor introduction can also be a powerful tool for preventing injury. Nicotinamide riboside is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to NAD+ . The present study investigated nicotinamide riboside's effect on endothelium functional state, microcirculation and intestinal morphology in acute mesenteric ischaemia and reperfusion. Mesenteric ischaemia was simulated after the adaptation period (15 minutes) by occluding the superior mesenteric artery for 60 minutes, followed by a reperfusion period of 30 minutes. The functional state of intestinal microcirculation was evaluated by laser Doppler flowmetry. Endothelial functional activity was studied by using wire myography. Intestinal samples were stained with haematoxylin and eosin for histological analysis. The results revealed that nicotinamide riboside protects the intestinal wall from ischaemia-reperfusion injury, as well as improving the relaxation function of mesenteric vessels. Nicotinamide riboside's protective effect in small intestine ischaemia-reperfusion can be used to reduce ischaemia-reperfusion injury, as well as to preserve intestinal grafts until transplant.

Mesenteric cysts and mesenteric venous thrombosis leading to intestinal necrosis in pregnancy managed with laparotomy: a case report and review of the literature.

BACKGROUND: Mesenteric cyst is a rare clinical entity especially in pregnancy; therefore, few cases have been reported in the literature. The standard method of their treatment is surgical excision either with laparotomy or laparoscopy. In addition, mesenteric vein thrombosis is a rare and life-threatening condition in pregnancy and needs immediate treatment because it can lead to intestinal necrotic ischemia. This is the first report of the coexistence of mesenteric cysts and mesenteric vein thrombosis during gestation. CASE PRESENTATION: A 27-year-old Greek woman, gravida 2 para 1, presented at 10 weeks' gestation to the Emergency Unit of our hospital complaining of diffuse abdominal pain which deteriorated the last 3 days, which was localized in her right iliac fossa, along with vomiting. She had undergone open laparotomy and right salpingo-oophorectomy at the age of 23 due to an ovarian cyst. Besides this, her personal and family medical history was unremarkable. She had never received oral contraceptives or any hormone therapy. On arrival, a clinical examination revealed tenderness on palpation of her right iliac fossa, without rebound tenderness or muscle guarding. Within 10 hours of hospitalization, her symptoms deteriorated further with rebound tenderness during the examination, tachycardia, and a drop of 12 units in her hematocrit value. An emergency laparotomy was performed. Two mesenteric cysts and a 60 cm necrotic part of her intestine were revealed intraoperatively. In the postoperative period, she complained of acute abdominal pain, tachycardia, and dyspnea. Computed tomography imaging revealed mesenteric vein thrombosis and pulmonary thromboembolism. She was treated with low molecular weight heparin and she was discharged on the 11th postoperative day. CONCLUSIONS: To the best of our knowledge, this is the first report in the literature of a simultaneous mesenteric cyst and mesenteric vein thrombosis in pregnancy. It is known that pregnancy is a state of hypercoagulation and clinicians should bear in mind this rare clinical condition in their diagnostic algorithm for acute abdominal pain.

Safety and Risk of Superselective Transcatheter Arterial Embolization for Acute Lower Gastrointestinal Hemorrhage with N-Butyl Cyanoacrylate: Angiographic and Colonoscopic Evaluation.

PURPOSE: To retrospectively evaluate the safety and risk of transcatheter arterial embolization (TAE) with N-butyl cyanoacrylate (NBCA) for urgent acute arterial bleeding control in the lower gastrointestinal tract by angiography and colonoscopy. MATERIALS AND METHODS: NBCA TAE was performed in 16 patients (mean age, 63.7 y) with lower gastrointestinal bleeding (diverticular hemorrhage, tumor bleeding, and intestinal tuberculosis). Angiographic evaluation was performed by counting the vasa recta filled with casts of NBCA and ethiodized oil (Lipiodol) after TAE. Patients were classified as follows: group Ia, with a single vas rectum with embolization of 1 branch (n = 6); group Ib, with a single vas rectum with embolization of ≥ 2 branches (n = 8); group II, with embolization of multiple vasa recta (n = 2). All patients underwent colonoscopy within 1 month, and ischemic complications (ulcer, scar, mucosal swelling, fibrinopurulent debris, and necrosis) were evaluated. RESULTS: The procedure was successful in all patients. No ischemic change was observed in any patients in group Ia and in two patients in group Ib. Ischemic changes were observed in six group Ib patients and both group II patients. Group Ib patients experienced ischemic complications that improved without treatment. One patient in group II underwent resection for intestinal perforation after embolization of three vasa recta. One patient in group II with sigmoid stricture with embolization of six vasa recta required prolonged hospitalization. CONCLUSIONS: NBCA embolization of ≥ 3 vasa recta can induce ischemic bowel damage requiring treatment. NBCA TAE of one vas rectum with ≥ 2 branches could also induce ischemic complications. However, these were silent and self-limited.

Management of Acute Mesenteric Ischemia: A Critical Review and Treatment Algorithm.

BACKGROUND: Acute mesenteric ischemia (AMI) due to a sudden loss or decrease in blood perfusion to the mesentery represents a highly lethal condition. However, the optimal surgical management remains debatable and merits a more clear recommendation based on a higher level of evidence. METHODS: A systematic review of articles published between 2000 and 2013 was performed. Patients were divided into endovascular treatment (ET), open surgery (OS), and hybrid technique (HT) groups. Data of patients' demographics, procedural information, clinical outcomes including mortality, morbidity, primary patency rate, technique success, primary intestinal resection rate, and second-look laparotomy rate, and follow-up were all retrieved. Comparison between the ET and the OS groups was made using 2-sided Student t test and 2-sided χ(2) test or Fisher exact test where appropriate. RESULTS: Twenty-eight articles with a total of 1110 patients were included for the review. The ET group had lower in-hospital mortality and morbidity but similar survival rate during follow-up compared to the OS group. The primary patency rate was higher in the ET group. The overall bowel resection rate was lower in the ET group, and nearly every patient in the cohort who required second-look laparotomy required bowel resection. The HT group seemed to have the lowest mortality and acceptable second-look laparotomy rate and morbidity. Comparison between the HT group and other groups was not possible due to the limited number of cases available for review. CONCLUSION: Endovascular treatment may serve as a first-line therapy for select patients when there is a low suspicion for intestinal necrosis. Open surgery should be reserved for emergency conditions requiring exploratory laparotomy. Hybrid technique may be an especially effective approach for treating AMI, with low morbidity and mortality, although further studies are required comparing it to OS and ET.

Right-Side Colon Ischemia: Clinical Features, Large Visceral Artery Occlusion, and Long-Term Follow-Up.

CONTEXT: Large visceral artery occlusion (LVAO) could underlie right-side colon ischemia (RSCI) but is little known. OBJECTIVE: To assess patients with RSCI through long-term follow-up, including features and management of LVAO. MAIN OUTCOME MEASURES: Mesenteric ischemia and mortality. DESIGN: Retrospective observational study in an integrated health care system. RESULTS: Of 49 patients (30 women [61.2%]; mean [standard deviation] age, 69.4 [11.9] years), 19 (38.8%) underwent surgery­that is, 5 (83.3%) of 6 who developed RSCI in hospital following surgical procedures and 14 (32.6%) of 43 who had RSCI before hospitalization (p value = 0.03); overall, 5 (10.2%) died. Among 44 survivors with a median (range) follow-up of 5.19 (0.03-14.26) years, 5 (11.4%), including 3 (20.0%) of 15 operated cases, had symptomatic LVAO and underwent angioplasty and stent placement: 2 for abdominal angina that preceded RSCI, 1 for acute mesenteric ischemia 1 week after resection of RSCI, 1 for RSCI 6 weeks after resection of left-side ischemia, and 1 for abdominal angina that began 3 years after spontaneous recovery from RSCI. None had further mesenteric ischemia until death from nonintestinal disease or the end of follow-up (1.6 to 10.2 years later). Kaplan-Meier survival estimates for all 44 survivors at 1, 3, 5, and 10 years were 88.6%, 72.3%, 57.6%, and 25.9%, respectively. Thirty-one patients (70.4%) died during follow-up, 19 (61.3%) of a known cause; the 39 patients not treated for LVAO lacked mesenteric ischemia. CONCLUSION: Patients with RSCI may have symptomatic LVAO; therefore, we advise they undergo careful query for symptoms of abdominal angina and routine visceral artery imaging.

Protective effects of L-alpha-glycerylphosphorylcholine on ischaemia-reperfusion-induced inflammatory reactions.

PURPOSE: Choline-containing dietary phospholipids, including phosphatidylcholine (PC), may function as anti-inflammatory substances, but the mechanism remains largely unknown. We investigated the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated PC derivative, in a rodent model of small intestinal ischaemia-reperfusion (IR) injury. METHODS: Anaesthetized Sprague-Dawley rats were divided into control, mesenteric IR (45 min mesenteric artery occlusion, followed by 180 min reperfusion), IR with GPC pretreatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to ischaemia) or IR with GPC post-treatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to reperfusion) groups. Macrohaemodynamics and microhaemodynamic parameters were measured; intestinal inflammatory markers (xanthine oxidoreductase activity, superoxide and nitrotyrosine levels) and liver ATP contents were determined. RESULTS: The IR challenge reduced the intestinal intramural red blood cell velocity, increased the mesenteric vascular resistance, the tissue xanthine oxidoreductase activity, the superoxide production, and the nitrotyrosine levels, and the ATP content of the liver was decreased. Exogenous GPC attenuated the macro- and microcirculatory dysfunction and provided significant protection against the radical production resulting from the IR stress. The GPC pretreatment alleviated the hepatic ATP depletion, the reductions in the mean arterial pressure and superior mesenteric artery flow, and similarly to the post-treatments with GPC, also decreased the xanthine oxidoreductase activity, the intestinal superoxide production, the nitrotyrosine level, and normalized the microcirculatory dysfunction. CONCLUSIONS: These data demonstrate the effectiveness of GPC therapies and provide indirect evidence that the anti-inflammatory effects of PC could be linked to a reaction involving the polar part of the molecule.