Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study.

BACKGROUND: This study aimed to explore the changes of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) expression on antigen-presenting cells (APCs) and evaluate their association with organ failure and mortality during early sepsis. METHODS: In total, 40 healthy controls and 198 patients with sepsis were included in this study. Peripheral blood was collected within the first 24 h after the diagnosis of sepsis. The expression of PD-L1 and PD-1 was determined on APCs, such as B cells, monocytes, and dendritic cells (DCs), by flow cytometry. Cytokines in plasma, such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, IL-10, and IL-17A were determined by Luminex assay. RESULTS: PD-1 expression decreased significantly on B cells, monocytes, myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) as the severity of sepsis increased. PD-1 expression was also markedly decreased in non-survivors compared with survivors. In contrast, PD-L1 expression was markedly higher on mDCs, pDCs, and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors. The PD-L1 expression on APCs (monocytes and DCs) was weakly related to organ dysfunction and inflammation. The area under the receiver operating characteristic curve (AUC) of the PD-1 percentage of monocytes (monocyte PD-1%)+APACHE II model (0.823) and monocyte PD-1%+SOFA model (0.816) had higher prognostic value than other parameters alone. Monocyte PD-1% was an independent risk factor for 28-day mortality. CONCLUSION: The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs. PD-L1 in monocytes and DCs was weakly correlated with inflammation and organ dysfunction during early sepsis. The combination of SOFA or APACHE II scores with monocyte PD-1% could improve the prediction ability for mortality.

Epidemiology of sepsis in Beijing from 2012 to 2018: analysis of hospital homepage databases derived from the Beijing Public Health System.

BACKGROUND: We aimed to evaluate the epidemiology of sepsis in secondary and tertiary hospitals in Beijing, China between 2012 and 2018 using information derived from the Beijing Public Health System. METHODS: The Beijing Public Health System accessed hospital homepage databases and identify patients who diagnosed sepsis or associated condition according to the International Classification of Diseases, 10th Edition, Clinical Modification codes. There are 125 hospitals involved in this study, including 61 secondary hospitals, accounting for 49.2%, and 63 tertiary hospitals, accounting for 50.8%. Patients were stratified by age as minors (0-17 years old), adults (18-64 years old), seniors (65-84 years old), and the elderly (≥ 85 years old). Patient's demographic information, treatments, outcomes, and all-cause hospitalization cost were evaluated. RESULTS: This study involved 8,597 patients. Patients treated in tertiary hospitals or received blood transfusion decreased with age, while patients who were male, received ventilation, or took Traditional Chinese Medicine, and in-hospital mortality and hospitalization cost, increased with age. There were 2,729 (31.7%) deaths in this study. A slight increase in in-hospital mortality occurred from 2012 to 2018. Median hospitalization cost for all patients was ¥29,453 (15,011, 65,237). Hospitalization cost showed no significant change from 2012 to 2016, but increased in 2017 and 2018. CONCLUSION: Sepsis is associated with high mortality and cost. From 2012 to 2018, in-hospital mortality and hospitalization cost of sepsis in Beijing increased significantly with age, and slightly by year.

Successful treatment of gastrointestinal infection-induced septic shock using the oXiris® hemofilter: A case report.

BACKGROUND: Septic shock leads to multiple organ failure, and bacterial endotoxins and endogenous cytokines play essential roles in the pathogenesis. The oXiris® hemofilter can efficiently adsorb endotoxins and cytokines. CASE SUMMARY: We admitted a critically ill 59 year-old male patient with gastrointestinal septic shock due to infection by a Gram-negative bacterium and septic acute kidney injury (AKI). Prior to intensive care unit admission, the patient reported intermittent diarrhea and decreased urine output. His blood pressure was 70/40 mmHg, necessitating fluid resuscitation and large doses of noradrenaline. Based on the results of a blood culture and the presence of hypotension, oliguria, and hypoxemia, we diagnosed septic shock, AKI, and multiple organ dysfunction. We administered continuous renal replacement therapy (CRRT) with an oXiris® hemofilter for 72 h with intermittent continuous veno-venous hemodiafiltration (CVVHDF), and changed the filter every 12 h. After his hemodynamic parameters were stable, we used a traditional filter (AN69 hemofilter) with intermittent CVVHDF. The 72 h CRRT with the oXiris® hemofilter led to stabilization of his vital signs, marked reductions in disease severity scores, and decreased levels of procalcitonin, endotoxin, and inflammatory factors. After 8 d of CRRT, his kidney function had completely recovered. CONCLUSION: We conclude that the oXiris® hemofilter combined with appropriate antibacterial therapy was an effective treatment for this patient with gastrointestinal septic shock.

Malaria-associated secondary hemophagocytic lymphohistiocytosis: A case report.

BACKGROUND: Malaria-associated secondary hemophagocytic lymphohistiocytosis (HLH) is rare. Moreover, the literature on malaria-associated HLH is sparse, and there are no similar cases reported in China. CASE SUMMARY: We report the case of a 29-year-old woman with unexplained intermittent fever who was admitted to our hospital due to an unclear diagnosis. The patient concealed her history of travel to Nigeria before onset. We made a diagnosis of malaria-associated secondary HLH. The treatment strategy for this patient included treatment of the inciting factor (artemether for 9 d followed by artemisinin for 5 d), the use of immunosuppressants (steroids, intravenous immunoglobulin) and supportive care. The patient was discharged in normal physical condition after 25 d of intensive care. No relapses were documented on follow-up at six months and 1 year. CONCLUSION: Early diagnosis of the primary disease along with timely intervention and a multidisciplinary approach can help patients achieve a satisfactory outcome.

Japanese encephalitis following liver transplantation: A rare case report.

BACKGROUND: Japanese encephalitis (JE) is a serious public health concern with a high mortality rate in many Asian countries. For many years, JE virus (JEV) was considered the major cause of viral encephalitis in Asia. Although most JE cases are asymptomatic, the case fatality rate approaches 30%, and approximately 30%-50% of survivors have long-term neurological sequelae. To the best of our knowledge, JEV infection has never been reported following liver transplantation. CASE SUMMARY: We report a case of a woman who underwent liver transplantation for autoimmune liver disease but presented with fever and neurological symptoms 13 d after transplantation. Magnetic resonance imaging revealed JEV infection, and positive immunoglobulin M antibody to JEV in blood and cerebrospinal fluid confirmed JE. The patient was treated with antiviral agents, immune regulation, and organ function support. No neurological sequelae were present after 1 year of follow-up. CONCLUSION: Imaging and lumbar puncture examination should be performed as soon as possible in patients with fever and central nervous system symptoms after liver transplantation, and the possibility of atypical infection should be considered, which is helpful for early diagnosis and improved prognosis.

Epidemiology of Sepsis-3 in a sub-district of Beijing: secondary analysis of a population-based database.

BACKGROUND: With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China. METHODS: The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution. RESULTS: Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) CONCLUSIONS:: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China. CLINICAL TRIAL REGISTRATION: NCT02285257, https://clinicaltrials.gov/ct2/show/record/NCT02285257.

Dietary approach to stop hypertension diet and risk of coronary artery disease: a meta-analysis of prospective cohort studies.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet can lower blood pressure, but its role in preventing coronary artery disease (CAD) remains in debate. Thus, we performed a meta-analysis of prospective cohort studies to address this issue. We carried out a systematical search in databases of PubMed and Embase to screen out eligible publications. Relative risks (RRs) of CAD in the included studies were summarised using random-effect meta-analysis. Dose-response association between DASH diet score and CAD risk was also evaluated. Seven prospective studies were finally included, with a total of 377,725 participants and 15,074 CAD cases. Compared to lower adherence, higher adherence to the DASH diet was associated a decreased risk of CAD (RR 0.82, 95% confidence interval [CI]: 0.78-0.87). Subgroup and sensitivity analyses supported the preventive effects of DASH diet against CAD, and there was no indication of publication bias. For a curvilinear dose-response pattern, the RRs (95% CIs) of CAD for the 4 knots (5th, 35th, 65th and 95th percentiles) of DASH diet score were 0.93 (0.89-0.98), 0.87 (0.80-0.95), 0.81 (0.72-0.90) and 0.74 (0.68-0.82), respectively. For a linear dose-response manner, each 4-point increase in the DASH diet score could reduce the risk of CAD by 5% (RR 0.95, 95% CI: 0.94-0.97). The results of our study indicate that higher adherence to the DASH diet confers a reduced risk of developing CAD.

Acute Kidney Injury in Critically Ill Patients with Sepsis: Clinical Characteristics and Outcomes.

Objective: The objectives of this study were to examine the clinical profile of critically ill patients with septic acute kidney injury (AKI) and to investigate clinical characteristics associated with the outcome of patients. Methods: Data from 582 critically ill patients were collected and retrospectively reviewed. Patients were divided into two groups: without AKI development and with AKI development. Baseline characteristics, laboratory, and other clinical data were compared between these two groups, and correlations between the characteristics and AKI development were examined. Patients with AKI development were further divided into two groups according to the survival outcome, and variables associated with the outcome were determined. Results: AKI was developed in 54.12% (n = 315) of patients, and these patients had blood pressure, SOFA score, APACHE II score, GCS, and various blood chemistry and hematology characteristics significantly different from the patients without AKI. Demographic characteristics (e.g. age and weight) were comparable between the two groups of patients. Among the 315 patients with AKI, 136 of them died during the study period. Multivariate logistic regression analysis revealed that the outcome of patients was associated with lung infection, coagulation system dysfunction, staphylococcus aureus infection, and use of various treatments (epinephrine, norepinephrine, and the use of mechanical ventilation) after AKI development. Conclusion: AKI occurred in approximately half of the critically ill patients admitted to ICU. The site and type of infections, as well as the use of vasopressor agents, were associated with the outcome.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

Correlation between different Chinese medicine syndromes and changes in microcirculation in septic shock patients.

OBJECTIVE: To investigate the correlation between different Chinese medicine (CM) syndromes and variations in microcirculation in septic shock patients. METHODS: seventy Septic shock patients were divided into four groups: heat damaging qi-yin group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases); excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient-blood group (HDNB, 11 cases). Sublingual microcirculation parameters were observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA), and parameters of microcirculation perfusion variations and prognoses were analyzed. RESULTS: Compared with those with qi-yin heat damage, perfused vessel density (PVD) in other groups decreased dramatically (P<0.05), and APACHE II scores increased significantly (P<0.05). In addition, the recovery time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05), and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the thermal injury camp blood group, sublingual microcirculation parameter variations showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were significant positive correlations between CM syndromes and APACHE II scoring in different groups (r=0.512, P<0.05). There were negative correlations between PVD and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in different patients. CONCLUSION: Sublingual microcirculation may serve as a clinical diagnostic parameter of the patient condition, as well as being a prognostic indicator.

Emodin improves lipopolysaccharide-induced microcirculatory disturbance in rat mesentery.

OBJECTIVE: Sepsis is a systemic inflammatory response syndrome. Emodin is a major ingredient of Rheum Palmatum, a Chinese herb that is widely used in China for treatment of endotoxemia-related diseases. This study intended to examine the effect of Emodin on LPS-induced rat mesenteric microcirculatory disturbance and the underlying mechanisms. METHODS: The male Wistar rats received LPS (5 mg/kg/hr) for 90 min, with or without administration of Emodin (10 mg/kg/hr) by enema 30 min before (pre-treatment) or after (post-treatment) LPS infusion, and the dynamics of mesenteric microcirculation were determined by inverted intravital microscopy. Expression of adhesion molecules and TLR4, NF-κB p65, ICAM-1, MPO, and AP-1 in mesentery tissue was evaluated by flow cytometry and Western-blot, respectively. RESULTS: Pre or post-treatment with Emodin significantly ameliorated LPS-induced leukocyte emigration, reactive oxygen species production and albumin leakage, and the expression of TLR4, NF-κB p65, ICAM-1, MPO and AP-1 in mesentery. CONCLUSIONS: These results demonstrate the beneficial role of Emodin in attenuating the LPS-induced microcirculatory disturbance, and support the use of Emodin for patients with endotoxemia.

[The clinical significance of determining the severity and prognosis by monitoring the changes in sublingual microcirculation in patients with severe sepsis].

OBJECTIVE: To investigate the clinical significance of dynamic monitoring of changes in the sublingual microcirculation in patients with severe sepsis to determine the degree of severity of the clinical condition and prognosis. METHODS: A prospective study was conducted. Sixty--five patients in the intensive care unit (ICU) in Beijing Friendship Hospital were enrolled from June 2010 to December 2010, among whom there were 30 cases of sepsis, 35 cases of severe sepsis. The severe sepsis patients received the early goal--directed resuscitation; and at 0 (before treatment), 6, 12, 24, 48, 72 hours after resuscitation, the technology of sidestream dark--field was used to measure the sublingual total vessel density (TVD), perfusing vessel density (PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) of sublingual microcirculation in patients and acute physiology and chronic health evaluation II (APACHEII) score, ICU days and 28--day mortality were recorded. Thirty healthy individuals were enrolled as the control group. RESULTS: The sublingual PPV and MFI were significantly lower in sepsis patients than those of the control group [PPV: (73.60 ± 16.77)% vs. (85.17 ± 7.60)%; MFI: 3.23 ± 0.77 vs. 3.78 ± 0.35, both P < 0.05]; PVD, PPV, MFI in severe sepsis patients were not only significantly lower than those of the sepsis group {PVD[mm/mm²]: 7.53 ± 4.38 vs.12.15 ± 2.88; PPV: (49.13 ± 33.74)% vs. (73.60 ± 16.77)%; MFI: 2.21 ± 1.41 vs. 3.23 ± 0.77, all P < 0.05}. After the early goal--directed fluid resuscitation, the sublingual microcirculation was improved significantly compared with that before treatment (0 hour), and they were remarkably apparent at 12 hours {TVD[mm/mm²]: 5.76 ± 2.25 vs. 6.72 ± 4.37; PVD [mm/mm²]: 7.57 ± 1.77 vs. 5.48 ± 4.39; PPV:(69.47 ± 19.24)% vs. (34.55 ± 30.82)%; MFI: 3.17 ± 0.49 vs. 1.55 ± 1.14, all P < 0.05}. Compared with the sepsis group, APACHEII score of the severe sepsis group was elevated (24.77 ± 7.45 vs. 19.30 ± 10.36, but P>0.05), the length of stay in ICU (days) was longer (20.60 ± 19.87 vs. 10.33 ± 9.53, P < 0.05), and the 28--day mortality was higher (45.71% vs. 36.36%, but P>0.05). In the severe sepsis group, compared with the survival group (19 cases), the sublingual microcirculation in the non-survival group (16 cases) PVD, PPV, MFI were significantly decreased{PVD[mm/mm²]:6.70 ± 5.15 vs. 8.53 ± 3.13; PPV: (44.23 ± 37.71)% vs. (54.96 ± 28.41)%; MFI: 1.89 ± 1.65 vs. 2.58 ± 0.98, P < 0.05 or P < 0.01}, but APACHEII score and length of stay in ICU (days) were not significantly different (23.19 ± 6.46 vs. 20.31 ± 6.03; 16.13 ± 10.90 vs. 19.19 ± 9.90, both P > 0.05). Correlation analysis showed that: PPV showed a significant negative correlation with the prognosis of the patients (r = -0.374, P < 0.05). CONCLUSION: Sequential monitoring of the sublingual microcirculation in patients with severe sepsis can be used to determine the disease severity, and to forecast the outcome of the patient.

[The effects of a histone deacetylase (HDAC) inhibitor on endotoxin-induced endothelial cell injury].

OBJECTIVE: To examine the effects of HDAC inhibitor trichostatin A (TSA) on lipopolysaccharide (LPS) induced genes expression in cultured endothelial cells in order to understand the mechanisms involved in the protection of endothelial cells against vascular endothelium injury during endotoxemia. METHODS: Cultured EAhy926 cells (a cell line with the features of vascular endothelial cells) were treated with LPS at 100 ng/ml [the dose was chosen for minimum impact on cell survival as determined using Methyl thiazolyl tetrazolium (MTT) assay], or LPS and TSA (100 µg/ml). The expressions of toll-like receptor 4 (TLR4) and HDAC2 were measured by Western blotting 3, 6, 9, 12 and 24 hours after the beginning of the treatment. RESULTS: The expressions of TLR4 (as measured by densitometry) was found significantly higher (P< 0.01) in LPS treated cells (1.01±0.14, 1.25±0.16, 1.20±0.19) 9, 12 and 24 hours after the beginning of the treatment as compared to untreated cells (0.34±0.05); The expression of HDAC2 was also found significantly higher (P< 0.01) after LPS treatment for 12 and 24 hours (1.14±0.10, 1.20±0.04) in comparison with untreated control (0.17±0.02). In LPS+TSA treated cells, TLR4 expression (0.37±0.07) was significantly lower (P< 0.05) after 12 hours of treatment in comparison with its LPS treated counterpart (1.25±0.16), while the level of TLR4 expression stayed unchanged 24 hours after the beginning of the treatment, as compared to the result at 12 hours (0.37±0.10 vs. 1.20±0.19, P> 0.05). No visible HDAC2 expression was detected in the cells treated with LPS+TSA. CONCLUSION: LPS stimulated the increase of TLR4 and HDAC2 expression in the vascular endothelial cells studied while TSA suppress the LPS induced TLR4 and HDAC2 expression in these cells.

Changes in intestinal mucosal immune barrier in rats with endotoxemia.

AIM: To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS: Male Wistar rats were randomly distributed into two groups: control group and lipopolysaccharide (LPS) group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold (M)-cells, dendritic cells (DCs), CD4(+) T cells, CD8(+) T cells, regulatory T (Tr) cells and IgA(+) B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin (IL)-4, interferon (IFN)-gamma and forkhead box P3 (Foxp3) in mucosal homogenates were measured by ELISA. The secretory IgA (sIgA) content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay. RESULTS: This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8(+) T cells, and IgA(+) B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4(+) T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-gamma increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased. CONCLUSION: Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunodeficiency.

[Experimental study on gut tolerance to early enteral nutrition following intestinal ischemia/reperfusion].

OBJECTIVE: To investigate the effects of early enteral nutrition (EEN) on intestinal function and gut tolerance after intestinal ischemia/reperfusion (I/R) injury. METHODS: Twenty-four male dogs were randomly divided into three groups: EEN only, I/R only and I/R+EEN. The superior mesenteric artery (SMA) was blocked for 1 hour followed by restoration of blood flow. EEN was given 4 hours after reperfusion by continuous infusion of Fresubin nutrition fluid (4 ml.kg(-1).h(-1), Fresenius Kabi Co, Germany) into gut via a tonometric catheter for 3 hours till intolerance symptoms, which including vomiting and diarrhea which indicated gut intolerance. CO(2) partial pressure of intestinal mucosa (PiCO(2)), D-xylose absorption and intestinal luminal pressure were measured to reflect intestinal function and perfusion. RESULTS: Incidence and severity of diarrhea and vomiting were significantly higher in I/R+EEN group (with 87.5% intolerance) than those in I/R only group (12.5%) and EEN only group (0). After EEN, PiCO(2) and intestinal cavity pressure were significantly higher, and the D-xylose absorption much lower, in the I/R+EEN group compared with the I/R group and EEN group (all P<0.01). CONCLUSION: Intestinal I/R may result in decreased tolerance to EEN. Too early enteral nutrition (less than 12 hours after gut hypoperfusion) may enhance intestinal ischemia injury and further inhibit its function of propulsion and absorption.