Lokmane Rahmania

970: USE OF A BIOMARKER SCORE IN PATIENTS WITH ACUTE RESPIRATORY DISTRESS SYNDROME

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) expression in many diseases, though the contribution of miRNAs to the pathophysiology of ALI remains obscure. We hypothesized that in ALI, dysregulated miRNAs modulate gene targets that control endothelial permeability leading to impaired barrier function. Methods: 8-week-old C57BL/6 mice were treated with intratracheal bleomycin or PBS. Lungs were collected at 4 or 7 days. miRNA expression was compared using a qPCR based 56-miRNA array. TargetScan and Enrichr were used to identify predicted gene targets and biological processes of 4 highly down-regulated miRNAs. Expression of 4 predicted miR-26a gene targets, EphA2, VEGFC, KDR and ROCK1 was evaluated by qPCR. EphA2 protein levels were measured by western blot analysis. In situ hybridization was performed to localize lung miR-26a. Human lung microvascular endothelial cells (HMVEC-L) were transfected with miR-26a mimic, inhibitor and negative controls. miR-26a, EphA2 mRNA/protein and cell permeability were measured. Results: Bleomycin decreased 4 miRNAs (miR-1, miR-26a, miR-30b and miR-30c) by greater than 6 fold. Of these miRNAs, miR-26a is predicted to regulate 135 genes involved in cell adhesion and relevant to ALI, including EphA2, VEGFC, KDR and ROCK1. Only lung EphA2 mRNA and protein significantly increased (1.7 fold and 1.5 fold) at 7 days. Transfection of HMEVC-L with miR-26a mimic significantly decreased EphA2 mRNA and protein (0.5 fold) and miR-26a inhibitor significantly increased EphA2 mRNA and protein (1.3 fold). Transfection with miR-26a inhibitor significantly increased HMVEC-L permeability at baseline and with VEGF stimulation, while transfection with miR-26a mimic had no impact. Conclusions: Multiple miRNAs are decreased in bleomycin-induced ALI. miR-26a, a putative regulator of genes involved in cell adhesion, regulated EphA2 expression and endothelial permeability in vitro. Future studies will interrogate targeted delivery systems for miRNA mimics and inhibitors as a novel therapeutic strategy.

Elevated endocan levels are associated with development of renal failure in ARDS patients.

Objectives The aim of the study was to determine whether plasma endocan levels were correlated with renal function in patients with acute respiratory distress syndrome (ARDS) and could predict the need for renal replacement therapy (RRT), as an indicator of acute renal dysfunction, during the ICU stay. Methods This was a post hoc analysis of prospectively collected data from 96 consecutive patients with ARDS (Berlin definition) who were not receiving RRT at diagnosis. Plasma endocan concentrations were measured using a quantitative ELISA method (Lunginov, France). We analyzed the predictive value of creatinine and endocan levels at diagnosis on the subsequent need for RRT using the area under the receiver operating characteristic curve (ROC AUC). We dichotomized values of creatinine (using a renal SOFA cut-off of 1.2 mg/dL) and endocan (best sensitivity and specificity based on the ROC curve) to predict need for RRT. All analyses were performed using SPSS 22.0 and a p value < 0.05 was considered as significant. Al values are presented as median with p25-75.

0888. Administration of tetrahydrobiopterin (BH4) protects renal microcirculation after ischemia and reperfusion

Abdominal aortic aneurysm surgery with supra-renal clamping is associated with potential development of renal insufficiency. Ischemia and reperfusion (I-R) produced during the procedure induces endothelial dysfunction with a decrease in tetrahydrobiopterin (BH4), a cofactor used in nitric oxide synthesis.