Continuous lumbar drainage after aneurysmal subarachnoid hemorrhage decreased malondialdehyde in cerebrospinal fluid and improved outcome.

PURPOSE: The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH. METHODS: Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured. RESULTS: There were 41 patients in non-LD group (age: 58.7 ± 13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3 ± 10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p = 0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (>60 years) (p = 0.0293), higher MDA level in the CSF (p = 0.0208), and delayed ischemic neurological deficit (p = 0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p < 0.001). CONCLUSION: The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

Effect of lordosis on adjacent levels after lumbar interbody fusion, before and after removal of the spinal fixator: a finite element analysis.

BACKGROUND: Literature indicates that adjacent-segment diseases after posterior lumbar interbody fusion with pedicle screw fixation accelerate degenerative changes at unfused adjacent segments due to the increased motion and intervertebral stress. Sagittal alignment of the spine is an important consideration as achieving proper lordosis could improve the outcome of spinal fusion and avoid the risk of adjacent segment diseases. Therefore, restoration of adequate lumbar lordosis is considered as a major factor in the long-term success of lumbar fusion. This study hypothesized that the removal of internal fixation devices in segments that have already fused together could reduce stress at the disc at adjacent segments, particularly in patients with inadequate lordosis. The purpose of this study was to analyze the biomechanical characteristics of a single fusion model (posterior lumbar interbody fusion with internal fixation) with different lordosis angles before and after removal of the internal fixation device. METHODS: Five finite element models were constructed for analysis; 1) Intact lumbar spine without any implants (INT), 2) Lumbar spine implanted with a spinal fixator and lordotic intervertebral cage at L4-L5 (FUS-f-5c), 3) Lumbar spine after removal of the spinal fixator (FUS-5c), 4) Lumbar spine implanted with a spinal fixator and non-lordotic intervertebral cage at L4-L5 (FUS-f-0c), and 5) Lumbar spine after removal of the spinal fixator from the FUS-f-0c model (FUS-0c). RESULTS: The ROM of adjacent segments in the FUS-f-0c model was found to be greater than in the FUS-f-5c model. After removing the fixator, the adjacent segments in the FUS-5c and FUS-0c models had a ROM that was similar to the intact spine under all loading conditions. Removing the fixator also reduced the contact forces on adjacent facet joints and reduced the peak stresses on the discs at adjacent levels. The greatest increase in stress on the discs was found in the FUS-f-0c model (at both L2/L3 and L3/L4), with intervertebral stress at L3/L4 increasing by 83% when placed in flexion. CONCLUSIONS: This study demonstrated how removing the spinal fixation construct after bone fusion could reduce intradiscal pressure and facet contact forces at adjacent segments, while retaining a suitable level of lumbar lordosis.

Prediction of Shunt Dependency After Intracerebral Hemorrhage and Intraventricular Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage is a disease with high morbidity and mortality. Extension of the hemorrhage into the ventricles is associated with the development of acute hydrocephalus and a poor outcome. Although it can be managed by external ventricular drainage (EVD), a subset of these patients require placement of permanent ventricular shunts. This study aimed to examine the factors on admission that can predict shunt dependency after EVD management. METHODS: Seventy-two patients who underwent EVD were included in this study. Seventeen of these patients underwent placement of a ventriculoperitoneal shunt. Variables analyzed included age, intraventricular hemorrhage (IVH) score, bicaudate index, acute hydrocephalus, initial Glasgow Coma Scale scores, and blood volume in each ventricle. RESULTS: In univariate analysis, IVH score (p = 0.020), bicaudate index (p < 0.001), blood volume in lateral ventricles (p = 0.025), blood volume in the fourth ventricle (p = 0.038), and the ratio of blood volume in lateral ventricles to that in third and fourth ventricles (p = 0.003) were significantly associated with persistent hydrocephalus. The best multiple logistic regression model included blood volume parameters and bicaudate index as predictors with the area under a receiver operating characteristic curve of 0.849. The variance inflation factor (VIF) showed that collinearity was not found among predictors. Patients diagnosed with acute hydrocephalus had less blood volume in the lateral ventricles (OR = 0.910) and had more blood volume in the third ventricle (OR = 3.174) and fourth ventricle (OR = 2.126). CONCLUSIONS: These findings may promote more aggressive monitoring and earlier interventions for persistent hydrocephalus after intraventricular hemorrhage in patients at risk.

Local hemostatic matrix for endoscope-assisted removal of intracerebral hemorrhage is safe and effective.

BACKGROUND/PURPOSE: Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. METHODS: The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. RESULTS: Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. CONCLUSION: This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings.

Effects of endotoxin absorber hemoperfusion on microcirculation in septic pigs.

BACKGROUND: Endotoxins contribute to systemic inflammatory response and microcirculatory dysfunctions under conditions of sepsis. Polymyxin B hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve clinical outcomes. This study aims to investigate the effect of PMX-HP on microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig model, we tested the hypothesis that PMX-HP can correct intestinal microcirculation, tissue oxygenation saturation, and histopathologic alterations. A total of 18 male pigs were divided into three groups: (1) sham; (2) sepsis (fecal peritonitis); and (3) sepsis + PMX-HP groups. A sidestream dark field video microscope was used to record microcirculation throughout the terminal ileal mucosa, colon mucosa, kidney surface, and sublingual area. A superficial tissue oxygenation monitor employing the light reflectance spectroscopy technique was used to measure the tissue oxygen saturation. Hematoxylin and eosin staining was used for histologic examination. RESULTS: The perfused small vessel density and tissue oxygen saturation of the ileal mucosa at 6 h were higher in the sepsis + PMX-HP group than those in the sepsis group. The fluid amount and norepinephrine infusion rate between the sepsis group and sepsis + PMX-HP groups did not differ significantly. The histologic score for the ileal mucosa was lower in the sepsis + PMX-HP group than that in the sepsis group. Finally, the urine output was higher in the sepsis + PMX-HP group than it was in the sepsis group. CONCLUSIONS: This study demonstrates that PMX-HP attenuates microcirculatory dysfunction, tissue desaturation, and histopathologic alterations in the ileal mucosa in septic pigs.

Distribution of Staphylococcal Cassette Chromosome (SCC) mec Element Types in Fusidic Acid-Resistant Staphylococcus epidermidis and Identification of a Novel SCC7684 Element.

We analyzed the staphylococcal cassette chromosome mec (SCCmec) types of 143 fusidic acid- and methicillin-resistant Staphylococcus epidermidis isolates. The most frequent SCCmec type was SCCmec III/SCCHg (53%), followed by SCCmec IV (29%). Clonal spreading of SCCmec III/SCCHg strains contributed to the increased prevalence of SCCmec III. A novel non-mec SCC structure, SCC7684, adjacent to SCCmec III, which carries a new ccrC allotype (ccrC3 allele 1) and contains heavy metal resistance genes, was identified in 14 isolates.

Novel Structure of Enterococcus faecium-Originated ermB-Positive Tn1546-Like Element in Staphylococcus aureus.

We determined the resistance determinants in 274 erythromycin-resistant methicillin-susceptible Staphylococcus aureus (MSSA) isolates during a 13-year period, 2000 to 2012. The resistance phenotypes, inducible macrolide-lincosamide-streptogramin (iMLS), constitutive MLS (cMLS), and macrolide-streptogramin (MS) resistance phenotypes, were examined by a double-disk diffusion D test. The ermB gene was more frequent (35%; 97/274) than ermC (27%; 75/274) or ermA (21%; 58/274). All 97 ermB-positive isolates harbored Tn551 and IS1216V The majority (89/97) of ermB-positive isolates displayed the cMLS phenotype and carried mobile element structure (MES)-like structures, which has been previously reported in sequence type 59 (ST59) methicillin-resistant S. aureus (MRSA). The remaining 8 ermB-carrying isolates, belonging to ST7 (n = 4), ST5 (n = 3), and ST59 (n = 1), were sasK intact and did not carry MES-like structures. Unlike a MES-like structure that was located on the chromosome, the ermB elements on sasK-intact isolates were located on plasmids by S1 nuclease pulsed-field gel electrophoresis (PFGE) analysis and conjugation tests. Sequence data for the ermB-containing region (14,566 bp) from ST59 NTUH_3874 revealed that the best match was a Tn1546-like element in plasmid pMCCL2 DNA (GenBank accession number AP009486) of Macrococcus caseolyticus Tn1546 is recognized as an enterococcal transposon and was known from the vancomycin resistance gene cluster in vancomycin-resistant Enterococcus (VRE). So far, acquisitions of Tn1546 in S. aureus have occurred in clonal complex 5 (CC5) MRSA, but not in MSSA. This is the first report that MSSA harbors an Enterococcus faecium-originated ermB-positive Tn1546-like element located on a plasmid.

Emergence of a small colony variant of vancomycin-intermediate Staphylococcus aureus in a patient with septic arthritis during long-term treatment with daptomycin.

OBJECTIVES: Small colony variants (SCVs) of Staphylococcus aureus are associated with persistent and drug-resistant infections. We demonstrated for the first time the emergence of SCVs in a patient with vancomycin-intermediate S. aureus (VISA) infection during long-term treatment with daptomycin. METHODS: A 73-year-old man with septic arthritis was infected with VISA. The patient was treated with daptomycin; however, the patient remained infected with VISA, with continuous isolation of VISA from his blood during long-term treatment. Five VISA isolates were characterized by: PFGE; genotyping including staphylococcal cassette chromosome mec (SCCmec), spa and MLST; antimicrobial susceptibility testing; and scanning and transmission electron microscopy. WGS and fatty acid analysis were also performed. RESULTS: The five VISA isolates were from a single clone of ST239/spa3(t037) and, of these, the first three were SCCmecIII positive and daptomycin susceptible, whereas the last two were SCCmecIII negative and daptomycin resistant and exhibited the characteristics of SCVs. The first and last isolates showed 13 remarkable genetic differences in SCCmec and the mprF, cls2, clpX and fabF genes. Of these, mutation of fabF (encoding the fatty acid synthase) seemed to be partially responsible for the slow growth and ultrastructural features, including an abnormal intercellular substance, and for the daptomycin resistance of SCVs. CONCLUSIONS: For the first time, we identified SCVs of VISA in a patient with septic arthritis during long-term treatment with daptomycin. Daptomycin-resistant SCVs of VISA were evolved in a stepwise manner and the mutation of fabF is likely responsible for the physical and ultrastructural characteristics and daptomycin resistance.

A novel fusidic acid resistance determinant, fusF, in Staphylococcus cohnii.

OBJECTIVES: To determine MICs of fusidic acid for and identify genetic determinants of resistance in Staphylococcus cohnii isolates. METHODS: Susceptibility to fusidic acid was determined by the standard agar dilution method in 24 S. cohnii subsp. urealyticus clinical isolates, 7 S. cohnii subsp. cohnii clinical isolates and 2 reference strains. Sequencing of a novel resistance determinant, fusF, and its flanking regions was performed by long and accurate PCR and inverse PCR. To evaluate the function of fusF, the MIC of fusidic acid was determined for recombinant Staphylococcus aureus carrying a plasmid expressing fusF. RESULTS: A total of 25 S. cohnii subsp. urealyticus (24 clinical isolates and 1 reference strain) and 2 S. cohnii subsp. cohnii displayed low-level resistance to fusidic acid (MICs 2-16 mg/L). Sequencing of a 4259 bp fragment from S. cohnii subsp. urealyticus ATCC 49330 revealed a novel resistance gene, designated fusF, which displayed 70.5% nucleotide and 67.3% amino acid identity to fusD. Expression of fusF in S. aureus confers resistance to fusidic acid. CONCLUSIONS: A novel FusB-family gene, fusF, was identified as a major resistance determinant in S. cohnii clinical isolates resistant to fusidic acid.

Wigner analysis of three dimensional pupil with finite lateral aperture.

A three dimensional (3D) pupil is an optical element, most commonly implemented on a volume hologram, that processes the incident optical field on a 3D fashion. Here we analyze the diffraction properties of a 3D pupil with finite lateral aperture in the 4-f imaging system configuration, using the Wigner Distribution Function (WDF) formulation. Since 3D imaging pupil is finite in both lateral and longitudinal directions, the WDF of the volume holographic 4-f imager theoretically predicts distinct Bragg diffraction patterns in phase space. These result in asymmetric profiles of diffracted coherent point spread function between degenerate diffraction and Bragg diffraction, elucidating the fundamental performance of volume holographic imaging. Experimental measurements are also presented, confirming the theoretical predictions.

In-line digital holographic imaging in volume holographic microscopy.

A dual-plane in-line digital holographic imaging method incorporating volume holographic microscopy (VHM) is presented to reconstruct objects in a single shot while eliminating zero-order and twin-image diffracted waves. The proposed imaging method is configured such that information from different axial planes is acquired simultaneously using multiplexed volume holographic imaging gratings, as used in VHM, and recorded as in-line holograms where the corresponding reference beams are generated in the fashion of Gabor's in-line holography. Unlike conventional VHM, which can take axial intensity information only at focal depths, the proposed method digitally reconstructs objects at any axial position. Further, we demonstrate the proposed imaging technique's ability to effectively eliminate zero-order and twin images for single-shot three-dimensional object reconstruction.

The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells.

Esophageal squamous cell carcinoma (ESCC), the most prevalent cell type of esophageal cancer, remains a dismal disease with poor prognosis. Photodynamic therapy (PDT) is a minimally invasive treatment option for early esophageal cancer. To explore possible factors involved in resistance to PDT in esophageal cancer cells, we selected PDT-resistant subcell lines by repeated treatment of CE48T/VGH (CE48T) ESCC cells with Photofrin-PDT and then analyzed the global gene modulations in the PDT-resistant cells by whole-genome microarray. More than 700 genes reached a fold change greater than 1.5 in each of the PDT-resistant cells compared to parental cells. Among these genes, both tumor necrosis factor (TNF) and EFNA1 genes were significantly upregulated in resistant cell lines. However, they were significantly downregulated in Photofrin-PDT-treated cells compared to untreated cells. The observations made in the microarray analysis were further confirmed by quantitative PCR. We observed that recombinant tumor necrosis factor alpha (TNF-α) activated the gene expression of EFNA1 at both the messenger RNA (mRNA) level and the protein level in CE48T cells. Functional analysis showed that when incubated with oligomeric and monomeric ephrin-A1 simultaneously, ESCC cells became significantly resistant to Photofrin-PDT. Functional analysis further suggested that transmembrane and soluble ephrin-A1 may cooperate to enhance resistance to Photofrin-PDT in ESCC cells.

Predicting long-term outcome after traumatic brain injury using repeated measurements of Glasgow Coma Scale and data mining methods.

Previous studies have identified some clinical parameters for predicting long-term functional recovery and mortality after traumatic brain injury (TBI). Here, data mining methods were combined with serial Glasgow Coma Scale (GCS) scores and clinical and laboratory parameters to predict 6-month functional outcome and mortality in patients with TBI. Data of consecutive adult patients presenting at a trauma center with moderate-to-severe head injury were retrospectively analyzed. Clinical parameters including serial GCS measurements at emergency department, 7th day, and 14th day and laboratory data were included for analysis (n = 115). We employed artificial neural network (ANN), naïve Bayes (NB), decision tree, and logistic regression to predict mortality and functional outcomes at 6 months after TBI. Favorable functional outcome was achieved by 34.8% of the patients, and overall 6-month mortality was 25.2%. For 6-month functional outcome prediction, ANN was the best model, with an area under the receiver operating characteristic curve (AUC) of 96.13%, sensitivity of 83.50%, and specificity of 89.73%. The best predictive model for mortality was NB with AUC of 91.14%, sensitivity of 81.17%, and specificity of 90.65%. Sensitivity analysis demonstrated GCS measurements on the 7th and 14th day and difference between emergency room and 14th day GCS score as the most influential attributes both in mortality and functional outcome prediction models. Analysis of serial GCS measurements using data mining methods provided additional predictive information in relation to 6-month mortality and functional outcome in patients with moderate-to-severe TBI.

A novel staphylococcal cassette chromosomal element, SCCfusC, carrying fusC and speG in fusidic acid-resistant methicillin-resistant Staphylococcus aureus.

A high prevalence of fusC (16/46, 59%) was found in fusidic acid-resistant methicillin-resistant Staphylococcus aureus isolates collected from 2008 to 2010. Nucleotide sequencing of fusC and flanking regions revealed a novel staphylococcal cassette chromosome (SCC) structure, SCCfusC, which was integrated into rlmH and located upstream from SCCmec. The SCCfusC element contained speG, which may contribute to the polyamine resistance.

Gemella parahaemolysans sp. nov. and Gemella taiwanensis sp. nov., isolated from human clinical specimens.

Four Gram-staining-positive, catalase-negative, coccoid isolates, designated NTUH_1465(T), NTUH_2196, NTUH_4957 and NTUH_5572(T), were isolated from human specimens. The four isolates displayed more than 99.6% 16S rRNA gene sequence similarity with Gemella haemolysans ATCC 10379(T), and 96.7 to 98.6% similarity with Gemella sanguinis ATCC 700632(T), Gemella morbillorum ATCC 27824(T) or Gemella cuniculi CCUG 42726(T). However, phylogenetic analysis of concatenated sequences of three housekeeping genes, groEL, rpoB and recA, suggested that the four isolates were distinct from G. haemolysans ATCC 10379(T) and other species. Isolates NTUH_2196, NTUH_4957 and NTUH_5572(T) clustered together and formed a stable monophyletic clade. DNA-DNA hybridization values among strains NTUH_1465(T) and NTUH_5572(T) and their phylogenetically related neighbours were all lower than 49%. The four isolates could be distinguished from G. haemolysans and other species by phenotypic characteristics. Based on the phylogenetic and phenotypic results, two novel species Gemella parahaemolysans sp. nov. (type strain NTUH_1465(T) = BCRC 80365(T) = JCM 18067(T)) and Gemella taiwanensis sp. nov. (type strain NTUH_5572(T) = BCRC 80366(T) = JCM 18066(T)) are proposed.

New structure of phage-related islands carrying fusB and a virulence gene in fusidic acid-resistant Staphylococcus epidermidis.

Nucleotide sequencing of the fusB-flanking regions in two fusidic acid-resistant Staphylococcus epidermidis isolates with the type IV aj1-leader peptide (LP)-fusB structure (lacking aj1) revealed that their fusB gene was located on novel phage-related islands inserted downstream of smpB and are here referred to as SeRIfusB-3692 and SePIfusB-857. The novel SePIfusB-857 structure was followed by SeCI857, forming a composite pathogenicity island which contained a putative virulence gene, vapE. The linkage of fusB and vapE may contribute to bacterial adaption.

Phase-coded volume holographic gratings for spatial-spectral imaging filters.

We present a design of phase-contrast filters embedded in a three-dimensional pupil to form phase-coded volume holographic gratings (VHGs) for spatial-spectral imaging. The phase-coded VHG improves image contrast and results in strong filtering properties to acquire weak phase structures of an object. In addition, incorporated with in-plane angle multiplexing, the multiplexed phase-coded VHGs enable obtaining weak phase information from multiple depths of an object. We experimentally demonstrate the multiplexed phase-coded VHGs for spatial-spectral imaging to enhance unstained features of spatial-spectral images of human breast cancer cells.

Correlation between early sublingual small vessel density and late blood lactate level in critically ill surgical patients.

BACKGROUND: Surgical stress may cause excessive inflammation and lead to microcirculatory dysfunction. The hypothesis of this study was that early microcirculatory dysfunction may result in anaerobic glycolysis and lead to elevated blood lactate levels in patients admitted to surgical intensive care units. METHODS: This prospective observational study enrolled adult patients admitted to surgical intensive care units after general surgery or thoracic surgery. We measured blood lactate levels before the operation and at 1 h and 24 h after the operation. We obtained images of sublingual microcirculation using a sidestream dark field video microscope and analyzed them employing automated analysis software. RESULTS: A total of 31 patients completed the study. Perioperative total and perfused small vessel densities were lower in patients with a blood lactate level ≥3 mmol/L. We observed a significant correlation between the total small vessel density at 1 h and the blood lactate level at 24 h (r = -0.573; P = 0.001). In addition, we saw a significant correlation between the perfused small vessel density at 1 h and the blood lactate level at 24 h (r = -0.476; P = 0.008). CONCLUSIONS: Early total and perfused small vessel density may be used as an early predictor or therapeutic goal for critically ill surgical patients in further studies.

The effects of Photofrin-mediated photodynamic therapy on the modulation of EGFR in esophageal squamous cell carcinoma cells.

Photodynamic therapy (PDT) has been demonstrated to be an effective minimally invasive treatment modality for early esophageal cancer. However, the molecular action in esophageal cancer during PDT is hardly known. EGFR has been known to downregulate in various cancer cells during PDT. In this study, we investigated the effects of Photofrin-mediated PDT on cell death and expression of EGFR in CE48T/VGH (CE48T) esophageal squamous cell carcinoma cells. We found that the photosensitizer Photofrin in the absence of light exposure can downregulate the expression of EGFR at both transcription and translation levels. Higher concentrations of Photofrin results in cytotoxicity whereas lower doses of Photofrin inhibit EGFR expression under dark control without inducing significant cell death. This Photofrin-associated inhibition of EGFR was repeated in lung cancer, cervical cancer, and glioblastoma cells. Another esophageal squamous cell carcinoma cell line CE81T/VGH (CE81T) was found to be resistant to Photofrin-induced inhibition of EGFR as well as to Photofrin-mediated dark toxicity compared with CE48T. The resistance to the cytotoxicity in CE81T cells became insignificant when the Photofrin-treated cells were further irradiated by red light (Photofrin-PDT). We suggest Photofrin modulates the expression of EGFR in cancer cells. However, efficient cell death still requires the combination of Photofrin and light irradiation in esophageal squamous cell carcinoma cells.

Enoxaparin sodium prevents intestinal microcirculatory dysfunction in endotoxemic rats.

INTRODUCTION: During severe sepsis or septic shock, activation of the inflammatory and coagulatory systems can result in microcirculatory dysfunction as well as microvascular thrombosis, culminating in multiple organ dysfunction and death. Enoxaparin can inhibit factor Xa and attenuate endothelial damage. The primary purpose of this study was to investigate the effect of enoxaparin on intestinal microcirculation in endotoxemic rats. METHODS: Thirty male Wistar rats were divided into the following three groups: sham operated (OP); lipopolysaccharide (LPS); and LPS + Enoxaparin group. The rats received a midline laparotomy to exteriorize a segment of terminal ileum for microcirculation examination by full-field laser perfusion imager and sidestream dark field video microscope on mucosa, muscle, and Peyer's patch. In the LPS and LPS + Enoxaparin groups, 15 mg/kg LPS was administered intravenously to induce endotoxemia, and 400 IU/kg enoxaparin sodium was also administered in the LPS + Enoxaparin group. RESULTS: At 240 minutes, the mean arterial pressure was higher in the LPS + Enoxaparin group than in the LPS group (93 ± 9 versus 64 ± 16 mm Hg, P < 0.001). Microcirculatory blood flow intensity was higher in the LPS + Enoxaparin group than in the LPS group as follows: mucosa (1085 ± 215 versus 617 ± 214 perfusion unit [PU], P < 0.001); muscle (760 ± 202 versus 416 ± 223 PU, P = 0.001); and Peyer's patch (1,116 ± 245 versus 570 ± 280 PU, P < 0.001). Enoxaparin inhibited LPS-induced reduction in perfused small vessel density and increase in heterogeneity of microcirculation. CONCLUSIONS: Enoxaparin can prevent intestinal microcirculatory dysfunction in endotoxemic rats by preventing microvascular thrombosis formation and maintaining normal mean arterial pressure.