Et of end-organ dysfunction (

Et of end-organ dysfunction (<12 hours) were included in a randomized, double-blind, placebo-controlled phase IIa study (2:1 ratio). An intravenous bolus injection of 67.5 U/kg bovine intestinal AP was followed by a maintenance dose of 177.5 U/kg for 24 hours. Arterial blood and urine were collected at different time points and analyzed for stable metabolites of NO. iNOS mRNA was determined by quantitative real-time RT-PCR using RNA isolated from renal cells in urine. The urinary excretion of the cytosolic glutathione S-transferase-A1 (GSTA1-1), a marker for proximal tubule damage, was measured using an ELISA. Data are depicted as the median (25?5 range). NO metabolites in blood were not significantly different between AP-treated (n = 10) and placebo-treated (n = 5) patients. However, the urinary excretion of NO metabolites decreased by 80 (75?5) from 227 (166?31) at baseline to 41 (28?4) ol/ 10 mmol creatinine (P < 0.05) after 24 hours of AP administration. After placebo treatment, the amount of urinary NO metabolites increased by 70 (45?70) (from 81 (64?19) to 628 (65?1,479) ol/10 mmol creatinine, P < 0.05). Baseline expression levels of iNOS in renal cells were PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/20799915 42-fold induced at baseline (vs healthful subjects), and AP administration reduced this induction by 80 ?5 (Niraparib carboxylic acid metabolite M1 Figure 1). Creatinine clearance improved by 45 (30?80) in sufferers treated with AP and declined by 25 (15?5) in placebo-treated patients. During the very first 24 hours the level of GSTA1-1 in urine of AP-treated sufferers decreased by 70 (50?0), compared with an increase of 200 (45?25) in placebo-treated patients, which correlated with urinary NO metabolites, indicating NO-induced proximal tubular damage. In conclusion, in septic sufferers, infusion of AP final results in an attenuated upregulation of iNOS and, subsequent, reduced NO production in the kidney, linked with an improvement in renal function.P15 Moderate hypothermia attenuates modifications in respiratory method mechanics and cytokine production in the course of low lung volume ventilation in ratsP Dostal1, M Senkerik1, V Cerny1, R Parizkova1, J Suchankova1, D Kodejskova1, D Bares1, P Zivny1, H Zivna2 1University Hospital Hradec Kralove, Czech Republic; 2Charles University in Prague, Faculty of Medicine Hradec Kralove, Czech Republic Crucial Care 2007, 11(Suppl two):P15 (doi: 10.1186/cc5175) Introduction Hypothermia was shown to attenuate ventilatorinduced lung injury (VILI) in high end-inspiratory lung volume models of VILI [1-3]. Experimental evidence suggests that moderate tidal volumes might, below specific clinical situations that induce alveolar instability, bring about a lung injury [4]. Current research have also suggested that insults like shock [5] or surgery [6] sensitize the lung to injury by priming for an exaggerated response to a second stimulus. The aim of this study was to investigate whether moderate hypothermia attenuates low lung volume injury during low PEEP, high FiO2 and moderate tidal volume ventilation in animals sensitized to injury by earlier anesthesia and surgery. Procedures Sixteen male adult Sprague awley rats, instrumented below ether anesthesia with vascular catheters on the previous day, were anesthetized, tracheostomized, connected to a ventilator and randomly allocated to groups of normothermia (37 ?0.5 , group N, n = eight) or hypothermia (33 ?0.5 , group H, n = 8). Following two hours of mechanical ventilation (FiO2 1,0, respiratory rate 60/min, tidal volume ten ml/kg, PEEP two cmH2O) inspiratory pressures were.