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.

H151, A SMALL MOLECULE INHIBITOR OF STING AS A NOVEL THERAPEUTIC IN INTESTINAL ISCHEMIA-REPERFUSION INJURY.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury is a severe disease associated with high mortality. Stimulator of interferon genes (STING) is an intracellular protein that is activated by cytosolic DNA and is implicated in I/R injury, resulting in transcription of type I interferons (IFN-α and IFN-ß) and other proinflammatory molecules. Extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, induces STING activation. H151 is a small molecule inhibitor of STING that has not yet been studied as a potential therapeutic. We hypothesize that H151 reduces inflammation, tissue injury, and mortality after intestinal I/R. Methods: In vitro, RAW264.7 cells were pretreated with H151 then stimulated with recombinant murine (rm) CIRP, and IFN-ß levels in the culture supernatant were measured at 24 hours after stimulation. In vivo, male C57BL/6 mice were subjected to 60-minute intestinal ischemia via superior mesenteric artery occlusion. At the time of reperfusion, mice were intraperitoneally instilled with H151 (10 mg/kg BW) or 10% Tween-80 in PBS (vehicle). Four hours after reperfusion, the small intestines, lungs, and serum were collected for analysis. Mice were monitored for 24 hours after intestinal I/R to assess survival. Results: In vitro, H151 reduced rmCIRP-induced IFN-ß levels in a dose-dependent manner. In vivo, intestinal levels of pIRF3 were increased after intestinal I/R and decreased after H151 treatment. There was an increase in serum levels of tissue injury markers (lactate dehydrogenase, aspartate aminotransferase) and cytokine levels (interleukin 1ß, interleukin 6) after intestinal I/R, and these levels were decreased after H151 treatment. Ischemia-reperfusion-induced intestinal and lung injury and inflammation were significantly reduced after H151 treatment, as evaluated by histopathologic assessment, measurement of cell death, chemokine expression, neutrophil infiltration, and myeloperoxidase activity. Finally, H151 improved the survival rate from 41% to 81% after intestinal I/R. Conclusions: H151, a novel STING inhibitor, attenuates the inflammatory response and reduces tissue injury and mortality in a murine model of intestinal I/R. H151 shows promise as a potential therapeutic in the treatment of this disease.

HOPX+ injury-resistant intestinal stem cells drive epithelial recovery after severe intestinal ischemia.

Intestinal ischemia is a life-threatening emergency with mortality rates of 50%-80% due to epithelial cell death and resultant barrier loss. Loss of the epithelial barrier occurs in conditions including intestinal volvulus and neonatal necrotizing enterocolitis. Survival depends on effective epithelial repair; crypt-based intestinal epithelial stem cells (ISCs) are the source of epithelial renewal in homeostasis and after injury. Two ISC populations have been described: 1) active ISC [aISC; highly proliferative; leucine-rich-repeat-containing G protein-coupled receptor 5 (LGR5+)-positive or sex-determining region Y-box 9 -antigen Ki67-positive (SOX9+Ki67+)] and 2) reserve ISC [rISC; less proliferative; homeodomain-only protein X positive (HOPX+)]. The contributions of these ISCs have been evaluated both in vivo and in vitro using a porcine model of mesenteric vascular occlusion to understand mechanisms that modulate ISC recovery responses following ischemic injury. In our previously published work, we observed that rISC conversion to an activated state was associated with decreased HOPX expression during in vitro recovery. In the present study, we wanted to evaluate the direct role of HOPX on cellular proliferation during recovery after injury. Our data demonstrated that during early in vivo recovery, injury-resistant HOPX+ cells maintain quiescence. Subsequent early regeneration within the intestinal crypt occurs around 2 days after injury, a period in which HOPX expression decreased. When HOPX was silenced in vitro, cellular proliferation of injured cells was promoted during recovery. This suggests that HOPX may serve a functional role in ISC-mediated regeneration after injury and could be a target to control ISC proliferation.NEW & NOTEWORTHY This paper supports that rISCs are resistant to ischemic injury and likely an important source of cellular renewal following near-complete epithelial loss. Furthermore, we have evidence that HOPX controls ISC activity state and may be a critical signaling pathway during ISC-mediated repair. Finally, we use multiple novel methods to evaluate ISCs in a translationally relevant large animal model of severe intestinal injury and provide evidence for the potential role of rISCs as therapeutic targets.

Evaluating the Risk of Irreversible Intestinal Necrosis Among Critically Ill Patients With Nonocclusive Mesenteric Ischemia.

INTRODUCTION: To identify factors associated with irreversible transmural necrosis (ITN) among critically ill patients experiencing nonocclusive mesenteric ischemia (NOMI) and to compare the predictive value regarding ITN risk stratification with that of the previously described Clichy score. METHODS: All consecutive patients admitted to the intensive care unit between 2009 and 2019 who underwent exploratory laparotomy for NOMI and who had an available contrast-enhanced computed tomography with at least 1 portal venous phase were evaluated for inclusion. Clinical, laboratory, and radiological variables were collected. ITN was assessed on pathological reports of surgical specimens and/or on laparotomy findings in cases of open-close surgery. Factors associated with ITN were identified by univariate and multivariate analysis to derive a NOMI-ITN score. This score was further compared with the Clichy score. RESULTS: We identified 4 factors associated with ITN in the context of NOMI: absence of bowel enhancement, bowel thinning, plasma bicarbonate concentration ≤15 mmol/L, and prothrombin rate <40%. These factors were included in a new NOMI-ITN score, with 1 point attributed for each variable. ITN was observed in 6%, 38%, 65%, 88%, and 100% of patients with NOMI-ITN score ranging from 0 to 4, respectively. The NOMI-ITN score outperformed the Clichy score for the prediction of ITN (area under the receiver operating characteristics curve 0.882 [95% confidence interval 0.826-0.938] vs 0.674 [95% confidence interval 0.582-0.766], respectively, P < 0.001). DISCUSSION: We propose a new 4-point score aimed at stratifying risk of ITN in patients with NOMI. The Clichy score should be applied to patients with occlusive acute mesenteric ischemia only.

Peritoneal dialysis-related peritonitis complicated with nonocclusive mesenteric ischemia.

Peritoneal dialysis (PD)-related peritonitis is a common complication of PD. Nonocclusive mesenteric ischemia (NOMI) is a rare complication of PD-related peritonitis, has a high mortality rate, and therefore should be detected early once it occurs. We describe a case of a 70-year-old woman on PD presented with moderate abdominal pain and low blood pressure, which contributed to the early diagnosis of PD-related peritonitis complicated with NOMI. Increased white cell count of 7150/µL (neutrophil, 84%) in dialysate effluent was diagnostic of PD-related peritonitis, which was later found to be caused by Pseudomonas putida. Computed tomography with contrast performed after administering crystalloids revealed hepatic portal venous gas, pneumatosis intestinalis in the ascending colon, and normal enhancement of the bowel wall and mesenteric arteries, which suggested a reperfusion of the previously ischemic ascending colon. Colonoscopy on hospital day seventeen revealed mucosal hemorrhage and ulcers in the entire right colon and the terminal ileum while the remaining colon was normal. These findings are compatible with the consequence of NOMI. Increased peak systolic velocity of the superior mesenteric artery (SMA) implied its stenosis. Past studies show that ischemia of the colon in patients with chronic kidney disease commonly occurs in the right colon. Arteriosclerosis of the SMA due to the long history of chronic kidney disease and diabetes might have caused its vulnerability to low blood pressure. Abdominal complications including NOMI should be screened for when a patient presents with low blood pressure and strong abdominal pain. This is the first case report that shows colonoscopy images of the colonic ulcers post-NOMI and PD-related peritonitis.

Three cases of non-occlusive mesenteric ischemia that developed after head and neck cancer therapy.

Non-occlusive mesenteric ischemia (NOMI) causes intestinal necrosis due to irreversible ischemia of the intestinal tract despite the absence of organic obstruction in the mesenteric blood vessels. The disease has extremely poor prognosis. We report three cases of NOMI hypothesized to have developed after head and neck cancer therapy; thus, we report these cases considering the available literature. Case 1: A 74-year-old man with T2N0M0 stage Ⅱ oropharyngeal carcinoma complained of abdominal pain 5 days after chemoradiotherapy. The patient was diagnosed with NOMI, and an emergency surgery was performed. Case 2: A 69-year-old man with T2N2bM0 stage IVA hypopharyngeal carcinoma complained of abdominal pain during TPF chemotherapy. The patient was diagnosed with NOMI, and he died on the same day. Case 3: A 82-year-old man with T2N2bM0 stage IVA hypopharyngeal carcinoma complained of abdominal pain with reduced level of consciousness, 5 days after total laryngopharyngectomy. The patient was diagnosed with NOMI, and an emergency surgery was performed on the same day. We therefore suggest that ENT physicians must be aware of NOMI as a complication that can develop after head and neck cancer therapy.

Protective Effects of Cinnamaldehyde against Mesenteric Ischemia-Reperfusion-Induced Lung and Liver Injuries in Rats.

The aim of this study was to characterize and reveal the protective effects of cinnamaldehyde (CA) against mesenteric ischemia-reperfusion- (I/R-) induced lung and liver injuries and the related mechanisms. Sprague-Dawley (SPD) rats were pretreated for three days with 10 or 40 mg/kg/d, ig of CA, and then induced with mesenteric ischemia for 1 h and reperfusion for 2 h. The results indicated that pretreatment with 10 or 40 mg/kg of CA attenuated morphological damage in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly restored the levels of aspartate transaminase (AST) and alanine transaminase (ALT) in mesenteric I/R-injured liver tissues, indicating the improvement of hepatic function. CA also significantly attenuated the inflammation via reducing myeloperoxidase (MOP) activity and downregulating the expression of inflammation-related proteins, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), cyclooxygenase-2 (Cox-2), and tumor necrosis factor receptor type-2 (TNFR-2) in both lung and liver tissues of mesenteric I/R-injured rats. Pretreatment with CA significantly downregulated nuclear factor kappa B- (NF-κB-) related protein expressions (NF-κB p65, NF-κB p50, I kappa B alpha (IK-α), and inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß)) in both lung and liver tissues of mesenteric I/R-injured rats. CA also significantly downregulated the protein expression of p53 family members, including caspase-3, caspase-9, Bax, and p53, and restored Bcl-2 in both lung and liver tissues of mesenteric I/R-injured rats. CA pretreatment significantly reduced TUNEL-apoptotic cells and significantly inhibited p53 and NF-κB p65 nuclear translocation in both lung and liver tissues of mesenteric I/R-injured rats. CA neither induced pulmonary and hepatic histological alterations nor affected the parameters of inflammation and apoptosis in sham rats. We conclude that CA alleviated mesenteric I/R-induced pulmonary and hepatic injuries via attenuating apoptosis and inflammation through inhibition of NF-κB and p53 pathways in rats, suggesting the potential role of CA in remote organ ischemic injury protection.

Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

Predicting Intestinal Ischaemia in Patients with Adhesive Small Bowel Obstruction: A Simple Score.

BACKGROUND/AIMS: Intestinal ischaemia (II) is the most critical factor to determine in patients with adhesive small bowel obstruction (ASBO) because intestinal ischaemia could be reversible. The aim of this study was to create a clinicoradiological score to predict II in patients with ASBO. METHODS: We conducted a retrospective study including 124 patients with ASBO. Logistic regression analysis was used to identify predictive factors of II. We assigned points for the score according to the regression coefficient. The area under the curve (AUC) was determined using receiver operating characteristic curves. RESULTS: Six independent predictive factors of II were identified: age, pain duration, body temperature, WBC, reduced wall enhancement and segmental mesenteric fluid at CT scan. According to the regression, coefficient points were assigned to each of the variables associated with II. The estimated rates of II were calculated for the total scores ranging from 0 to 24. The AUC of this clinicoradiological score was 0.92. A cut-off score of 6 was used for the low-probability group (the risk of II was 1.13%). A score ranging from 7 to 15 defined intermediate-probability group (the risk of II was 44%). A score ≥16 defined high-probability group (100% of patients in this group had II). CONCLUSIONS: We performed a score to predict the risk of intestinal II with a good accuracy (the AUC of our score exceeded 0.90). This score is reliable and reproducible, so it can help surgeon to prioritize patients with II for surgery because ischaemia could be reversible, avoiding thus intestinal necrosis.

Prognostic factors in acute mesenteric ischemia and evaluation with multiple logistic regression analysis effecting morbidity and mortality.

<b>Background:</b> Acute mesenteric ischaemia (AMI) is a catastrophic abdominal emergency characterized by sudden critical interruption to the intestinal blood flow which commonly leads to bowel infarction and death. AMI still has a poor prognosis with an in-hospital mortality rate of 50-69 %. This high mortality rate is related to the delay in diagnosis which is often diffucult and overlooked. Early intervention is crucial and the potential for intestinal viability. <br><b>Methods:</b> The charts of 140 patients who were hospitalazed with AMI between May 1997 and August 2013 in Ege University Faculty of Medicine, department of general surgery were retrospectively reviewed. Demographical and clinical features of patients determining the best predictors which effect on morbidity and mortality were evaluated by Multiple Logistic Regression analysis by Enter method after adjustment for all possible confounding factors. <br><b>Results:</b> After Multiple LR analysis by Enter method after adjustment for all possible confounding factors affecting morbidity; shock, exploration and stay in hospital were statistically significant. Age, cardiac comorbidities, ASA scores, the time delay between onset of acute abdominal pain to surgery, the presence of acidosis and shock, the involved organs (small bowel and both), type of surgery and medical treatment and small bowel length under 100 cm were statistically significant on mortality. <br><b>Conclusion:</b> Risk factors related to mortality and morbidity have been poorly analyzed due to lack of prospective studies and smaller number of patients. Early diagnosis generally depends on clinical awareness and suspicion. Age and time of delay between onset of acute abdominal pain to surgery longer than 24 hours are the most important parameters that predict the mortality for patients presenting with shock and acidosis.

Incidence and risk factors of portomesenteric venous thrombosis after colorectal surgery for cancer in the elderly population.

BACKGROUND: Although it is known that portomesenteric venous thrombosis (PMVT) is associated with total colectomy and proctocolectomy in young patients with inflammatory bowel disease, little is known about incidence and risk factors of PMVT among the elderly population undergoing colorectal surgery for cancer. METHODS: Data of elderly patients (> 70 years) undergoing surgery for colorectal cancer were retrospectively registered. The occurrence of PMVT was correlated with the patients' characteristics and operative variables. Data collected included age, sex, obesity, ASA score, tumor degree, type of surgical resection, surgical approach (laparoscopic or open), and duration of surgery (from skin incision to the application of dressings). RESULTS: A total of 137 patients > 70 years who underwent surgery for colorectal cancer and developed an acute intraabdominal process with suggestive symptoms, needing a CT scan, were included. Three of these patients (2.1%) had portomesenteric venous thrombosis during the study period, which was proved with CT scan. There were no significant patients' characteristics or operative variables between patients with or without the occurrence of PMVT after surgery. Of interest, only operative time was significantly higher in patients with PMVT after surgery (256 ± 40 vs 140 ± 41, p < 0.001). CONCLUSIONS: PMVT as a cause of abdominal pain after colorectal surgery for cancer in the elderly population is uncommon. An index of suspicion for PMVT in an elderly postoperative colorectal cancer patient with sudden onset of abdominal pain must be maintained.

Interleukin-6 Therapy Improves Intestinal Recovery Following Ischemia.

BACKGROUND: Interleukin-6 (IL6) has both proinflammatory and anti-inflammatory pathways, but its effects on intestinal recovery following ischemia are unknown. We hypothesized that administration of IL6 following intestinal ischemia would improve mesenteric perfusion and mucosal injury. METHODS: Adult male C57Bl6J mice were anesthetized, and a laparotomy was performed. Baseline intestinal perfusion was assessed by laser Doppler imaging. Intestinal ischemia was induced for 60 min by temporarily occluding the superior mesenteric artery. After ischemia, treatments were administered intraperitoneally before closure (Vehicle: 250 µL phosphate-buffered-saline, IL6 low dose (20 ng), IL6 medium dose (200 ng), or IL6 high dose (2 µg)). Animals were allowed to recover for 24 h, were reanesthetized, and their mesenteric perfusion was reassessed. Perfusion was expressed as percentage of baseline. Animals were then sacrificed, and the intestines were explanted for histological analysis. Separate frozen samples were homogenized and analyzed by ELISA for vascular endothelial growth factor (VEGF) and interferon gamma-induced protein 10. RESULTS: IL6 increased mesenteric perfusion in low dose groups only, whereas it improved postischemic mucosal injury scores in both low and medium dose groups. No differences in perfusion or histology were seen when high dose IL6 was utilized. Intestinal VEGF was higher in the low dose IL6 group compared to vehicle, whereas IP-10 levels were lower in low and medium dose groups compared to vehicle. No differences were noted compared to vehicle in intestinal VEGF and IP-10 with high dose IL6 therapy. CONCLUSIONS: Lower doses of IL6 may serve as effective therapy to decrease intestinal injury after ischemia. Further studies are needed to elucidate the downstream mechanisms before widespread clinical use.

Oral Antibiotics Reduce Intestinal Necrosis in Acute Mesenteric Ischemia: A Prospective Cohort Study.

OBJECTIVES: To identify treatments likely to prevent progression towards irreversible transmural intestinal necrosis (ITIN) in acute mesenteric ischemia (AMI). METHODS: Prospective observational cohort study from a French intestinal stroke center. Multivariate analysis using a time-dependent Cox regression model. RESULTS: Between 2009 and 2015, 67 patients with AMI were included. ITIN occurred in 34% of patients and mortality was 13%. Oral antibiotics was independently associated with a decreased risk of ITIN (HR: 0.16 (95% CI = 0.03-0.62); p = 0.01). CONCLUSIONS: By decreasing luminal bacterial load and translocation, oral antibiotics in addition to early revascularization might reduce progression of AMI to ITIN.

Comparison of the diagnostic values of vascular adhesion protein-1 and intestinal fatty acid-binding protein in the diagnosis of acute mesenteric ischemia.

OBJECTIVES: The aim of this study is to compare the diagnostic values of plasma levels of vascular adhesion protein-1 (VAP-1) and intestinal fatty acid-binding protein (I-FABP) for diagnosing acute mesenteric ischemia (AMI). METHODS: The study used a randomized, controlled experimental design. Forty-two female Sprague-Dawley rats were divided into three control groups and three ischemia groups. Plasma VAP-1 and I-FABP levels were measured, and the extent of ischemic damage was determined using a histopathological damage score in terminal ileum tissue samples. RESULTS: In the early phase of AMI (i.e. at the 30-min time point), VAP-1 levels did not differ between the control and ischemia groups (p > 0.05), but I-FABP levels were significantly higher in the ischaemia groups (p = 0.017). Although both VAP-1 and I-FABP levels increased in the ischaemia groups, only VAP-1 levels showed a significant increase compared to the control group at the 2-h time point (p = 0.011). Ischemic damages associated with AMI became the most prominent at the 6-h time point. During this phase, both VAP-1 and I-FABP levels were significantly higher in the ischemia groups than in the control groups (p = 0.007 and p = 0.002, respectively). Both VAP-1 and I-FABP levels showed a significant correlation with ischemic changes, but a higher correlation was observed for VAP-1 levels (r = 0.771). CONCLUSIONS: Both I-FABP and VAP-1 levels were useful for diagnosing AMI, but VAP-1 levels correlated better with the extent of ischaemic damage.

The role of ischemic preconditioning in the expression of apoptosis-related genes in a rat model of intestinal ischemia-reperfusion injury

Abstract Purpose: To analyze the effects of ischemic preconditioning (IPC) in the expression of apoptosis-related genes in rat small intestine subjected to ischemia and reperfusion. Methods: Thirty anesthetized rats underwent laparotomy and were drive into five groups: control (CG); ischemia (IG); ischemia and reperfusion (IRG); IPC and ischemia (IG+IPC); IPC and ischemia and reperfusion (I/RG+IPC). Intestinal ischemia was performed by clamping the superior mesenteric artery for 60 minutes, whereas reperfusion lasted for 120 minutes. IPC was carried out by one cycle of 5 minutes of ischemia followed by 10 minutes of reperfusion prior to the prolonged 60-minutes-ischemia and 120-minutes-reperfusion. Thereafter, the rats were euthanized and samples of small intestine were processed for histology and gene expression. Results: Histology of myenteric plexus showed a higher presence of neurons presenting pyknotic nuclei and condensed chromatin in the IG and IRG. IG+IPC and I/RG+IPC groups exhibited neurons with preserved volume and nuclei, along with significant up-regulation of the anti-apoptotic protein Bcl2l1 and down-regulation of pro-apoptotic genes. Moreover, Bax/Bcl2 ratio was lower in the groups subjected to IPC, indicating a protective effect of IPC against apoptosis. Conclusion: Ischemic preconditioning protect rat small intestine against ischemia/reperfusion injury, reducing morphologic lesions and apoptosis.

Use of long saphenous vein graft in acute on chronic mesenteric ischaemia.

Acute mesenteric ischaemia is a relatively rare surgical emergency, but despite advances in diagnostic tests, the mortality of this condition remains stubbornly high (50%-80%). This is principally because of the non-specific nature of the presenting symptoms and subsequent delay in diagnosis. We report an unusual case of acute mesenteric ischaemia treated by emergency laparotomy, small bowel resection and revascularisation using reversed long saphenous vein graft.

Regulation of systemic tissue injury by coagulation inhibitors in B6.MRL/lpr autoimmune mice.

Impaired fibrinolysis and complement activation in Systemic Lupus Erythematosus contributes to disease amplification including increased risk of thrombosis and tissue Ischemia/Reperfusion (IR) injury. Previous work has demonstrated complement is a key regulator of tissue injury. In these studies inhibitors had varying efficacies in attenuating injury at primary versus systemic sites, such as lung. In this study the role of coagulation factors in tissue injury and complement function was evaluated. Tissue Factor Pathway Inhibitor (TFPI), an extrinsic pathway inhibitor, and Anti-Thrombin III, the downstream common pathway inhibitor, were utilized in this study. TFPI was more effective in attenuated primary intestinal tissue injury. However both attenuated systemic lung injury. However, ATIII treatment resulting in enhanced degradation of C3 split products in lung tissue compared to TFPI. This work delineates the influence of specific early and late coagulation pathway components during initial tissue injury versus later distal systemic tissue injury mechanism.

Diazoxide reduces local and remote organ damage in a rat model of intestinal ischemia reperfusion.

BACKGROUND: Intestinal ischemia reperfusion is a common clinical condition that causes functional impairment. Once tight junctions are damaged, barrier function is compromised, and the intestines become a source for entry of bacterial and inflammatory mediators into the circulation, leading to systemic inflammatory response syndrome, multiple organ failure, and death. It is possible that diazoxide could protect the intestines against ischemia reperfusion. The aim of this study is to determine whether diazoxide can provide protection in a rat model of intestinal ischemia reperfusion. METHODS: A total of 32 adult male specific pathogen-free Wistar rats were randomized into three groups: a control group, n = 6; a saline group, n = 13; and a diazoxide group, n = 13. The saline and diazoxide groups underwent clamping of the superior mesenteric artery for 1 h, with samples in all the groups being collected 12 h later. RESULTS: Intestinal histology showed greater damage in the intestinal ischemia reperfusion groups. mRNA expression of zonula occludens-1 and occludin (tight junction proteins) and interleukin-6 and cyclooxygenase-2 was the highest in the Saline group. The Diazoxide group showed a reduction in aspartate aminotransferase serum levels compared with the other groups. CONCLUSIONS: Increased expression of zonula occludens-1, occludin, and cyclooxygenase-2 suggested a greater regenerative effort because of more severe lesions in the saline group. In addition, increased expression of interleukin-6 in the saline group was suggestive of inflammation, indicating that diazoxide had protective effects in the diazoxide group. Reduced aspartate aminotransferase in the diazoxide group suggested liver protection. Diazoxide protects the intestines and liver from intestinal ischemia reperfusion lesions in rats.