Accuracy of citrulline, I-FABP and D-lactate in the diagnosis of acute mesenteric ischemia.

Early diagnosis of acute mesenteric ischemia (AMI) remains a clinical challenge, and no biomarker has been consistently validated. We aimed to assess the accuracy of three promising circulating biomarkers for diagnosing AMI-citrulline, intestinal fatty acid-binding protein (I-FABP), and D-lactate. A cross-sectional diagnostic study enrolled AMI patients admitted to the intestinal stroke center and controls with acute abdominal pain of another origin. We included 129 patients-50 AMI and 79 controls. Plasma citrulline concentrations were significantly lower in AMI patients compared to the controls [15.3 µmol/L (12.0-26.0) vs. 23.3 µmol/L (18.3-29.8), p = 0.001]. However, the area under the receiver operating curves (AUROC) for the diagnosis of AMI by Citrulline was low: 0.68 (95% confidence interval = 0.58-0.78). No statistical difference was found in plasma I-FABP and plasma D-lactate concentrations between the AMI and control groups, with an AUROC of 0.44, and 0.40, respectively. In this large cross-sectional study, citrulline, I-FABP, and D-lactate failed to differentiate patients with AMI from patients with acute abdominal pain of another origin. Further research should focus on the discovery of new biomarkers.

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.

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.

Normal Lactate and Unenhanced CT-Scan Result in Delayed Diagnosis of Acute Mesenteric Ischemia.

INTRODUCTION: To investigate the factors associated with a delayed diagnosis (DD) of acute mesenteric ischemia (AMI). METHODS: An observational cohort study from an intestinal failure center. The primary outcome was DD >24 hours. RESULTS: Between 2006 and 2015, 74 patients with AMI were included and 39 (53%) had a DD. Plasma lactate <2 mmol/L (odd ratio: 3.2; 95% confidence interval: 1.1-9.1; P = 0.03) and unenhanced computed tomography scan (odds ratio: 5.9; 95% confidence interval: 1.4-25.8; P = 0.01) were independently associated with DD. DISCUSSION: Suspicion of AMI should no longer be affected by normal plasma lactate levels and should prompt evaluation by a contrast-enhanced computed tomography-scan.

[Lactate and acute mesenteric ischemia: diagnostic value]. / Lactate et ischémie mésentérique aiguë†: utilité diagnostique.

Acute mesenteric ischemia is a rare diagnosis with a very high mortality rate. It is often suspected in case of severe abdominal pain, disproportional to the findings of physical examination. The definite diagnosis is confirmed by CT-angiography and surgical exploration, but the measurement of blood L-lactate often takes place during the diagnostic work-up when this pathology is suspected. This review shows that there is no biological marker with sufficient sensitivity and specificity to confirm or rule out acute mesenteric ischemia. L-lactate measurement is easy to perform, but its diagnostic performance is insufficient to avoid a CT-angiography, whatever the pre-test clinical probability of acute mesenteric ischemia. These conclusions are supported by the current recommendations of the World Society of Emergency Surgery.

L'ischémie mésentérique aiguë est un diagnostic rare au taux de mortalité très élevé. Elle est souvent suspectée en cas de douleurs abdominales sévères et disproportionnelles aux résultats de l'examen physique. Le diagnostic définitif s'obtient par angio-CT et exploration chirurgicale, mais le dosage du L-lactate intervient fréquemment lors de la stratégie diagnostique au moment de la suspicion clinique. Cet article met en évidence qu'il n'existe pas de marqueur biologique unique suffisamment sensible et spécifique pour confirmer ou exclure une ischémie mésentérique aiguë. Le dosage du L-lactate est rapide, mais sa performance diagnostique ne permet pas de surseoir à l'angio-CT, et ce quelle que soit la probabilité clinique prétest d'ischémie mésentérique. Ces conclusions sont soutenues par les recommandations des sociétés de chirurgie.

Absence of the C5a Receptor C5aR2 Worsens Ischemic Tissue Injury by Increasing C5aR1-Mediated Neutrophil Infiltration.

Neutrophil infiltration to ischemic tissues following reperfusion worsens injury. A key driver of neutrophil recruitment and activation is the complement factor C5a, which signals through two receptors, C5aR1 and C5aR2. In this study, we used a neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to investigate the underexplored role of C5aR2 in neutrophil mobilization, recruitment, and disease outcomes. We show that intestinal IR induces rapid neutrophil mobilization along with a concomitant reduction in plasma C5a levels that is driven by both C5aR1 and C5aR2. Intestinal IR in C5aR2-/- mice led to worsened intestinal damage and increased neutrophil infiltration. Inhibition of C5aR1 signaling in C5aR2-/- mice with PMX53 prevented neutrophil accumulation and reduced IR pathology, suggesting a key requirement for enhanced neutrophil C5aR1 activation in the absence of C5aR2 signaling. Interestingly, C5aR2 deficiency also reduced circulating neutrophil numbers after IR, as well as following G-CSF-mediated bone marrow mobilization, which was independent of C5aR1, demonstrating that C5aR2 has unique and distinct functions from C5aR1 in neutrophil egress. Despite enhanced tissue injury in C5aR2-/- IR mice, there were significant reductions in intestinal proinflammatory cytokines, highlighting complicated dual protective/pathogenic roles for C5aR2 in pathophysiology. Collectively, we show that C5aR2 is protective in intestinal IR by inhibiting C5aR1-mediated neutrophil recruitment to the ischemic tissue. This is despite the potentially local pathogenic effects of C5aR2 in increasing intestinal proinflammatory cytokines and enhancing circulating neutrophil numbers in response to mobilizing signals. Our data therefore suggest that this balance between the dual pro- and anti-inflammatory roles of C5aR2 ultimately dictates disease outcomes.

Validation of the American Association for the Surgery of Trauma grading system for acute mesenteric ischemia-More than anatomic severity is needed to determine risk of mortality.

BACKGROUND: Acute mesenteric ischemia (AMI) is a highly morbid disease with a diverse etiology. The American Association for the Surgery of Trauma (AAST) proposed disease-specific grading scales intended to quantify severity based upon clinical, imaging, operative, and pathology findings. This grading scale has not been yet been validated for AMI. The goal of this study was to evaluate the correlation between the grading scale and complication severity. METHODS: Patients for this single center retrospective chart review were identified using diagnosis codes for AMI (ICD10-K55.0, ICD9-557.0). Inpatients >17 years old from the years 2008 to 2015 were included. The AAST grades (1-5) were assigned after review of clinical, imaging (computed tomography), operative and pathology findings. Two raters applied the scales independently after dialog with consensus on a learning set of cases. Mortality and Clavien-Dindo complication severity were recorded. RESULTS: A total of 221 patients were analyzed. Overall grade was only weakly correlated with Clavien-Dindo complication severity (rho = 0.27) and mortality (rho = 0.21). Computed tomography, pathology, and clinical grades did not correlate with mortality or outcome severity. There was poor interrater agreement between overall grade. A mortality prediction model of operative grade, use of vasopressors, preoperative serum creatinine and lactate levels showed excellent discrimination (c-index = 0.93). CONCLUSION: In contrast to early application of other AAST disease severity scales, the AMI grading scale as published is not well correlated with outcome severity. The AAST operative grade, in conjunction with vasopressor use, creatinine, and lactate were strong predictors of mortality. LEVEL OF EVIDENCE: Prognostic study, III.

Hepatic portal venous gas with pneumatosis intestinalis secondary to mesenteric ischemia in elderly patients: Two case reports.

INTRODUCTION: Hepatic portal venous gas (HPVG) is a rare imaging finding. When HPVG is accompanied with pneumatosis intestinalis (PI), the underlying cause is usually mesenteric ischemia with consequent intestinal necrosis. This combination of clinical conditions is associated with a poor prognosis. In this study, we present the cases of 2 elderly patients with HPVG and PI secondary to mesenteric ischemia. PATIENT CONCERNS: In case 1, a 89-year-old male patient was admitted to intensive care unit with respiratory failure, On the fifth day of admission, he developed a high fever (39.5°C) and abdominal distension. In case 2, a 92-year-old male patient admitted to our intensive care unit and received mechanical ventilation due to acute respiratory failure. During the treatment, the patient developed gastrointestinal bleeding. On physical examination, abdominal bulging and tense abdominal walls were detected. Both patients underwent abdominal contrast-enhanced computed tomography, showed abundant HPVG with PI. DIAGNOSES: The patients were diagnosed as acute mesenteric ischemia, bowel necrosis, septic shock, multiple organ dysfunction syndrome based on computed tomography scan, abdominal signs, and laboratory tests. INTERVENTIONS: Fluid resuscitation, high-dose vasopressors, and intravenous antibiotic therapy were given. OUTCOMES: Despite prompt treatment, the condition of both patients rapidly deteriorated, and the patients died shortly thereafter. CONCLUSION: Mesenteric ischemia is a clinical emergency. In patients with risk factors and abdominal signs, the clinical suspicion for this condition should be high. Although rare, both HPVG and PI are important radiological clues that usually indicate the presence of mesenteric ischemia with consequent intestinal necrosis.

Predictive and prognostic value of L-lactate, D-dimer, leukocyte, C-reactive protein and neutrophil/lymphocyte ratio in patients with acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia (AMI) is a disease that causes an ischemia in the intestines due to the obstruction of the mesenteric vessels feeding the intestines, with a mortality rate reaching up to 80%. The overall incidence of AMI is 0.63 per 100,000 people. Early diagnosis and treatment are very important for survival. There is no ideal biomarker that can reflect different types and stages of AMI. This study investigated the predictive and prognostic value of L-lactate, D-dimer, leukocyte, C reactive protein (CRP) and neutrophil/lymphocyte ratio (NLR) in the preoperative period were investigated in patients operated for AMI. METHODS: A total of 44 patients operated for AMI between 2015 and 2019 were evaluated in this study. Demographic, clinical, radiological, laboratory and surgical findings of the patients included in this study were recorded. The patients were divided into groups according to the etiological type of AMI. L-lactate, D-dimer, CRP, leukocyte, and NLR levels of these patients were determined. Statistical analysis was performed according to AMI groups. RESULTS: The mean age of the 44 patients included in this study was 67.7 years and the female to male ratio was 0.76. According to tomography results, 31.8% (n=14) of the patients had mesenteric artery embolism, 29.5% (n=13) had mesenteric artery thrombus, 25% (n=11) had mesenteric vein thrombus and 13.6% (n=6) had non-occlusive mesenteric ischemia. When AMI types were compared, D-dimer and CRP levels were found to be significantly different from other markers. The total length of stay in the hospital was found to be significantly correlated with the L-lactate (p=0.047) and CRP (p=0.045) levels. In the analyses, CRP was determined to be the common biomarker that could be used in the diagnosis of mesenteric ischemia in all AMI types. CONCLUSION: Particularly, the CRP level can be used effectively in the preoperative period to diagnose AMI and to determine its subtype and clinical course. However, L-lactate, D-dimer, leukocyte and NLR are markers that have no predictive value in the diagnosis of all AMI subtypes.

Sensitivity and Specificity of the Platelet-Lymphocyte Ratio and the Neutrophil-Lymphocyte Ratio in Diagnosing Acute Mesenteric Ischemia in Patients Operated on for the Diagnosis of Mesenteric Ischemia: A Retrospective Case-Control Study.

Aim: The present study aims to determine whether various hematological parameters and ratios of patients could be used to diagnose AMI. Materials and Methods: The subjects of the study are the patients who were hospitalized with an acute mesenteric ischemia (AMI) pre-diagnosis and underwent surgery as a consequence. The patients who were determined to have the diagnosis of AMI intraoperatively are categorized in the AMI Group. The patients whose operations do not reveal AMI (negative exploration) are categorized in the Control Group. These two groups are compared in terms of hematological parameters and rates. Results: In the study, the PLR (p = 0.017), NLR (p = 0.33), PDW (0.023), RDW (p = 0.025) values are significantly higher in the AMI group compared to the control group while the LYMP (p = 0.023) count is significantly lower. Conclusions: For the patients admitted to the emergency clinics with suspected AMI, the increased PLR, NLR, PDW, and RDW values together with the reduced lymphocyte count can be used to support the diagnosis.

Prothrombin Arg541Trp Mutation Leads to Defective PC (Protein C) Pathway Activation and Constitutes a Novel Genetic Risk Factor for Venous Thrombosis.

OBJECTIVE: Defective PC (protein C) pathway predisposes patients to venous thromboembolism (VTE) and is mostly, but not exclusively, attributed to hereditary PC or PS (protein S) deficiencies and activated PC resistance caused by factor V Leiden mutation. Approach and Results: In a patient with acute mesenteric venous thrombosis and positive family history of VTE associated with the impaired PC pathway function determined by thrombin generation test, we identified a novel heterozygous prothrombin mutation p.Arg541Trp. Two more patients with positive family history of VTE carrying the same mutation were identified in a cohort of another 373 unrelated patients, making an overall prevalence of 0.8%. Family investigation revealed 11 individuals in the 3 pedigrees harboring the heterozygous prothrombin p.Arg541Trp mutation, and 8 of them (72%) had experienced episodes of VTE. Functional studies indicated the mutation moderately decreased procoagulant activity of prothrombin and had mild impact on the inactivation of thrombin by its inhibitor antithrombin. However, the amino acid residue substitution significantly compromised PC activation by thrombin, both in the absence and presence of soluble thrombomodulin, and thus rendered prothrombin function procoagulant biased. CONCLUSIONS: In summary, the prothrombin p.Arg541Trp mutation constitutes a new genetic risk factor of VTE by impairing function of PC pathway and tilting thrombin's procoagulant activity over anticoagulant function.

May Nesfatin-1 be a Biomarker in Acute Mesenteric Ischemia?

OBJECTIVE: To investigate the diagnostic value of nesfatin-1 in cases of intestinal ischemia and ischemia/reperfusion. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: The Experimental Animals Laboratory of Bezmialem University, in June 2018. METHODOLOGY: Twenty-one healthy male Sprague Dawley rats were randomly divided into three groups of 7 rats each. In group 1: 1-hour intestinal ischemia followed by 5-hour reperfusion was performed. In group 2: rats were subjected to 6-hour intestinal ischemia. In group 3: rats underwent laparotomy and closure without performing any further procedure. Changes in leukocyte count, amylase, blood sugar, LDH, SGOT, CRP, and nesfatin-1 levels were determined. For histopathological examination, a small intestinal sample was taken and preserved in 10% formaldehyde. RESULTS: Nesfatin-1 value in group 2 was significantly higher than that in group 1 and group 3 (p=0.005, and p <0.001 respectively). Nesfatin-1 value in group 1 was significantly higher than that in group 3. A significant (r = 0.864/p <0.001) positive correlation was observed between nesfatin-1 value and pathology score. The pathology score of group 2 was significantly higher than that of group 1 and group 3 (p <0.001). CONCLUSION: Serum nesfatin-1 can be a biomarker in acute mesenteric ischemia.

Platelet to lymphocyte ratio as a predictive factor of 30-day mortality in patients with acute mesenteric ischemia.

INTRODUCTION: Acute mesenteric ischemia is associated with high rates of mortality. The aim of this study was to investigate the prognostic value of the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on 30-day outcomes in patients with acute mesenteric ischemia. MATERIAL AND METHODS: Consecutive patients who were admitted for an acute mesenteric ischemia were retrospectively included. The full white blood count at the time of admission to the hospital was recorded. The population was divided into 4 subgroups according to the quartiles of the NLR and the PLR. The 30-day outcomes including the mortality and the complications were compared among the subgroups. RESULTS: In total, 106 patients were included. A surgical treatment including revascularization and/or digestive resection was performed for 56 patients (52.8%). The 30-day all-cause mortality was 72 patients (67.9%). Patients with higher PLR value (PLR >429.3) had significantly higher rate of mortality compared to the other groups (80.8% vs 46.2%, 66.7% and 77.8%, p = 0.03). No significant difference on 30-day outcome was observed among the subgroups divided according to the NLR. CONCLUSION: The PLR, but not the NLR, is a predictive factor of 30-day mortality in patients with acute mesenteric ischemia.

[Biomarkers for acute mesenteric ischemia diagnosis: state of the art and perspectives]. / Biomarqueurs diagnostiques de l'ischémie mésentérique aiguë : état des lieux et perspectives.

Acute mesenteric ischemia (AMI) is one of the most severe diagnostic and therapeutic vital emergencies. This affection is characterized by the insufficient blood supply to the gastrointestinal tract, related to an occlusive or non-occlusive mechanism, resulting in an ischemic and inflammatory injury that may progress to necrosis of the intestinal wall. The clinical picture is nonspecific, dominated by acute abdominal pain. At present, no early biological marker is commonly used in clinical practice for diagnostic purposes. The purpose of this review was to review the markers that have been evaluated in this condition. Among the biological blood markers which have shown a diagnostic interest in the IMA, there are notably the two stereoisomers of lactate (D and L), D-dimers, and alpha glutathione transferase. More specific markers include the intestinal fatty acid binding protein or I-FABP, which is a marker of enterocyte necrosis, citrulline, a marker of enterocyte mass, or Smooth muscle protein 22 (SM22) marker for muscle damage. The early diagnosis of intestinal ischemia remains a challenge. It is likely that in the future IMA's biomarker research will be better customized and adapted to the physiopathological mechanism. More global approaches (proteomics, metabolomics) should also make it possible to identify new biomarkers.

Neutrophil-to-lymphocyte ratio and mesenteric ischemia: can it predict the etiology of mesenteric ischemic at computed tomography?

OBJECTIVES: To assess the usefulness of the neutrophil-to-lymphocyte ratio (NLR) as a predictive factor of acute mesenteric ischemia (AMI) in patients presenting at the emergency department (ED) with acute abdominal pain. METHODS: This is a retrospective case-control study of patients older than 16 years admitted to the ED with acute abdominal pain with CT and histologic confirmation. The study group corresponded to patients with abdominal CT with radiological signs of AMI. The control group corresponded to patients with non-AMI findings in abdominal CT. Association measurements of NLR with radiological signs were compared with a paired-sample t test, and multivariate regression performed to analyze potential correlations. To assess the diagnosis capacity of NLR, ROC curves were calculated. RESULTS: A total of 61 patients were included (32 cases and 29 controls). The cases of AMI showed higher mortality (43.8% vs 6.9%, p < 0.01) and higher NLR on the limit of statistical significance (13.8 vs 8.7, p = 0.053). Patients with AMI due to occlusion of the superior mesenteric artery (SMA) showed a higher NLR (8.3 vs 22.3, p < 0.001). The area under the curve (AUC) of the NLR for AMI due to occlusion of the SMA was 0.88 (95% CI 0.7-1.0, p = 0.001). No patient with NLR < 5 presented AMI due to occlusion of the SMA. An NLR of 12.8 showed a sensitivity of 92% and a specificity of 74% for AMI due to occlusion of SMA. CONCLUSIONS: The NLR is a useful parameter of AMI of arterial origin due to occlusion of the SMA; it can help the clinician to raise suspicion of this diagnosis and the interpreting radiologist in the acquisition protocol for the CT study and would alert for an early surgical treatment.

Perfusion-related changes in intestinal diffusion detected by NMR-MOUSE® monitoring in minipigs.

OBJECTIVE: The aim was to investigate perfusion-related changes in the intestinal diffusion assessed by NMR-MOUSE monitoring in minipigs. This was a follow-up study of previous experiments on landrace pigs demonstrating the feasibility of NMR-MOUSE monitoring in large animals. METHODS: 5 mature female minipigs (mean body weight 50 ±â€¯2 kg) underwent laparotomy with exposition of several small intestinal loops and their feeding vessels. The loops were examined consecutively using NMR-MOUSE monitoring for assessment of intestinal proton diffusion (fast diffusion component [FC] and slow diffusion component [SC]) and oxygen to see monitoring (O2C, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory evaluation. Following a baseline measurement on each loop under physiological perfusion, measurements were continued as one of the following main treatments were performed per loop: method 1 - ischemia; method 2 - flow reduction; method 3 - intraluminal glucose followed by ischemia; method 4 - intraluminal glucose followed by flow reduction. Perioperative monitoring was supplemented by blood gas analyses and histopathological assessment of H.E. stained intestinal biopsies. RESULTS: The NMR-MOUSE measurement showed a significant difference in the change to baseline values in the FC during flow reduction compared to the other treatments according to the unadjusted (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0005, pM2 vs. M4 = 0.0005) and the adjusted p-values (pM2 vs. M1 < 0.0001, pM2 vs. M3 = 0.0030, pM2 vs. M4 = 0.0030). In the SC, the difference between ischemia and flow reduction was significant according to the unadjusted p-values (pM2 vs. M1 = 0.0397). Whereas the FC showed a trend towards ongoing increase during ischemia but towards ongoing decrease during flow reduction, the SC showed contrary trends. These effects seemed to be attenuated by prior glucose application. According to the results of O2C monitoring, ischemia as well as flow reduction caused a significant decrease of microcirculatory oxygen saturation (inner probe: methods 1-4 and outer probe methods 1, 2: p < 0.0001; outer probe: pM2 = 0.0001), velocity (inner probe: pM1 < 0.0001, pM2 = 0.0155, pM3 = 0.0027; outer probe: pM1 < 0.0001, pM2 = 0.0045, pM3 = 0.0047, pM4 = 0.0037) and serosal flow (outer probe, methods 1 and 2: p < 0.0001; pM3 = 0.0009, pM4 = 0.0008). The histopathological analysis showed a significant association with time (p = 0.003) but not with the experimental method (p = 0.1386). CONCLUSIONS: Intestinal diffusion is affected significantly by perfusion changes in mature minipigs. As shown by NMR-MOUSE monitoring, ischemia and flow reduction have contrary effects on intestinal diffusion and, additionally, the fast and slow diffusion components show opposite trends during each of those pathological perfusion states. Prior intraluminal glucose application seems to attenuate the effects of malperfusion on intestinal diffusion.

Heat Shock Protein 70 Messenger RNA in Rat Leukocytes Elevates After Severe Intestinal Ischemia-Reperfusion.

BACKGROUND: Heat shock protein 70 (HSP70) confers protection against heat shock, oxidative stress, infection, and inflammation in many cell types. A recent study reported that the induction of HSP70 was associated with morphologic protection against ischemia-reperfusion injury (IRI) in the rat small intestine. This study investigated the dynamics of HSP70 in leukocytes during intestinal IRI in a rat model. MATERIALS AND METHODS: Serial blood samples were collected at 60-minute intervals up to 240 min from male Wistar rats (n = 15). The rats were divided into three groups of five each: the control group, the nonlethal IRI group, and the lethal IRI group. Rats belonging to the control group underwent a sham operation, and laparotomy was performed on rats in the lethal and nonlethal IRI groups. The nonlethal group experienced a 30-minute clamping of the superior mesenteric artery, and the lethal group experienced a 75-minute clamping of the superior mesenteric artery. The expression of HSP70 messenger RNA (mRNA) in leukocytes was measured by real-time quantitative polymerase chain reaction. Mixed-effects modeling of repeated measures was used to carry out the statistical analysis. The Bonferroni correction was applied to multiple comparisons. A P value < 0.0167 was considered to indicate statistical significance. RESULTS: The expression of HSP70 mRNA in leukocytes increased 60 min after reperfusion in both IRI groups, and it was 12.8 times higher in the lethal group and 3.6 times higher in the nonlethal group compared with the control group. The expression of mRNA in the lethal group was significantly increased compared with the nonlethal group and the control group at 120 and 180 min after reperfusion. At 120 min after reperfusion, the expression of HSP70 mRNA was 6.1 times higher in the lethal group than in the nonlethal group (P = 0.0075) and 17.7 times higher than in the control group (P = 0.0011). At 180 min after reperfusion, the expression of HSP70 mRNA was 6.8 times higher in the lethal group than in the nonlethal group (P = 0.0007) and 4.3 times higher than in the control group (P = 0.0032). Although the expression of HSP70 mRNA in the nonlethal group was elevated in the early stages of reperfusion, there was no difference between the nonlethal group and the control group (P = 0.0212 at 60 min). CONCLUSIONS: The expression of HSP70 mRNA in leukocytes may be a clinically useful indicator for evaluating pathologic conditions in intestinal IRI.

The role of heparin-binding protein in the diagnosis of acute mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a high mortality rate, yet diagnostic difficulties persist. Although many biomarkers have been investigated for diagnostic purposes, as well as imaging methods, a sufficiently specific and sensitive marker has not been identified. This research was designed to examine whether heparin-binding protein (HBP), which has a role in the early phase of inflammation, could be useful in the diagnosis of AMI. METHODS: Serum samples obtained from a previously performed rabbit model of AMI were used in the study. HBP, C-reactive protein (CRP) and interleukin 6 (IL-6) levels were measured in blood samples obtained at baseline and 1, 3, and 6 hours from subjects that were separated into 3 groups: control, sham, and ischemia. The change in each marker over time and comparisons of the groups were evaluated statistically. RESULTS: A significant difference was not detected at the first hour in any of the studied markers. At the third hour, the CRP and IL-6 levels in the ischemia group indicated a significant increase in comparison with the control and sham groups (p<0.001). The HBP values showed a significant increase at the sixth hour in the ischemia group in comparison with the others (p<0.001). CONCLUSION: The HBP level demonstrated a slower increase in a rabbit model of AMI compared with CRP and IL-6. However, it still has the potential to become an early diagnostic biomarker. Diagnostic sensitivity and specificity should be evaluated in further clinical trials.

What predicts the outcome in patients with intestinal ischemia? A single center experience.

BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a mortality of 60-80%. Early diagnosis and rapid treatment have a decisive influence on therapy. The aim of this study was to evaluate the prognostic value of AMI markers on mortality, in order to better anticipate the clinical course and to initiate therapeutic steps at an early stage. STUDY DESIGN: An analysis from our prospective database of 302 consecutive patients with AMI who were treated surgically in the Department of General Surgery between February 2003 and October 2014 was performed. Uni- and multivariate analysis of risk factors for mortality have been performed in the total cohort and in two subgroups according to their stay in intensive care unit (ICU) at the time of AMI diagnosis. RESULTS: Of the 302 patients with AMI, 115 were in ICU at the time of diagnosis. Totally, 203 patients underwent computed tomography scan (CT-scan) of the abdomen for diagnosis and 68% of them showed specific signs of AMI. A total of 63 (21%) embolectomies were performed during the surgical procedure. The post-operative mortality rate was 68% (204 patients). Among survivors, 85 (87%) patients developed a short bowel syndrome in the post-operative course. Multivariate analysis showed a significant association between mortality and preoperative lactate>3mmol/L, C-reactive protein>100mg/L and ICU stay at the time of AMI diagnosis. CONCLUSION: Mortality of patients with AMI remains high. Elevated lactate, elevated C-reactive protein and ICU stay are factors associated with increased mortality. Their presence in a patient with suspicion of AMI should trigger a multidisciplinary management in emergency.