No relationship between plasma glutamine concentration and the endogenous glutamine production was seen. Key messages The hypothesized reduction in endogenous glutamine production during intravenous glutamine supplementation selleck chemicals in critically ill patients was not seen. There was no relationship between endogenous Inhibitors,Modulators,Libraries glutamine production and plasma glutamine concentration in critically ill patients. The bolus injection technique to measure glutamine Inhibitors,Modulators,Libraries rate of appearance was useful for repetitive measurements in critically ill patients. Introduction In acute respiratory failure mechanical ventilation is a life saving intervention Inhibitors,Modulators,Libraries without alternatives, but MV may cause ventilator induced lung injury. Since clinical trials have been highlighting the impact of VILI on ARDS mortality, lung protective ventilation has been widely implemented in clinical practice.

However, clinical and experimental studies provide evidence that VILI occurs despite low tidal volume ventilation and that particularly preinjured lungs Inhibitors,Modulators,Libraries are susceptible for the development of VILI. Lung injury worsened in ventilated mice upon infection with Staphylococcus aureus even under protective ventilation strategies, which is intriguing as pneumonia is the leading cause of ARDS and sepsis. However a major limitation of this and other studies was that mice were infected after initiation of MV. Experimental studies investigating the impact of VILI in established pneumonia, i. e. when the immune system is already activated and lung mechanics are changed due to pneumonic infiltrates, would be of particular clinical relevance.

VILI has been linked to multiple organ failure. Improved understanding of the impact of VILI on the progression of pneumonia towards sepsis with its detrimental complications Inhibitors,Modulators,Libraries is desirable. Thus, we implemented a new second hit model of established pneumococcal pneumonia and MV. While the risk of ARDS development may be reduced by lowering tidal volumes, MV with low tidal volumes still seems to aggravate lung injury and further tidal volume reduction is limited by hypercapnia, which aggravates acidosis. Thus, adjuvant pharmacotherapies in addition to protective ventilation are needed to further limit VILI. Adrenomedullin, an endogenous 52 amino acid peptide belonging to the calcitonin gene related peptide family is crucial for regulation of endothelial barrier integrity.

AM binds to the calcitonin receptor like receptor assembled with receptor activity modifying proteins 1 3, thereby raising intracellular cAMP levels in endothelial cells and reducing myosin light chain phosphorylation. Consequently, interendothelial gap selleck products formation is prevented. Exogenous AM reduced pulmonary hyperpermeability in experimental ALI and sepsis, and we identified AM as being protective against VILI and associated kidney injury in previously healthy mice by stabilizing endothelial barrier function and microcirculation.