Serial inflammatory biomarkers of the severity, course and outcome of late onset acute respiratory distress syndrome in critically ill patients with or at risk for the syndrome after new-onset fever.

Aim: Accurate biomarkers of the acute respiratory distress syndrome (ARDS) may help risk stratification and management. We assessed the relation between several biomarkers and the severity, course and outcome of late onset ARDS in 101 consecutive critically ill patients with new onset fever.

Materials And Methods: On study days 0, 1, 2 and 7 we measured angiopoietin-2 (ANG2), pentraxin-3 (PTX3), interleukin-6 (IL-6), procalcitonin (PCT) and midregional proadrenomedullin (proADM).

Opposing effects of the angiopoietins on the thrombin-induced permeability of human pulmonary microvascular endothelial cells.

Background: Angiopoietin-2 (Ang-2) is associated with lung injury in ALI/ARDS. As endothelial activation by thrombin plays a role in the permeability of acute lung injury and Ang-2 may modulate the kinetics of thrombin-induced permeability by impairing the organization of vascular endothelial (VE-)cadherin, and affecting small Rho GTPases in human pulmonary microvascular endothelial cells (HPMVECs), we hypothesized that Ang-2 acts as a sensitizer of thrombin-induced hyperpermeability of HPMVECs, opposed by Ang-1.

Methodology/principal Findings: Permeability was assessed by measuring macromolecule passage and transendothelial electrical resistance (TEER).

Plasma protein levels are markers of pulmonary vascular permeability and degree of lung injury in critically ill patients with or at risk for acute lung injury/acute respiratory distress syndrome.

Objectives: To evaluate the diagnostic value of plasma protein levels for pulmonary vascular permeability and acute respiratory distress syndrome. During acute lung injury and acute respiratory distress syndrome, increased vascular permeability induces protein-rich fluid extravasation. We hypothesized that plasma protein levels predict increased vascular permeability and acute respiratory distress syndrome.

Circulating angiopoietin-2 levels in the course of septic shock: relation with fluid balance, pulmonary dysfunction and mortality.

Purpose: To investigate whether angiopoietin-2, von Willebrand factor (VWF) and angiopoietin-1 relate to surrogate indicators of vascular permeability, pulmonary dysfunction and intensive care unit (ICU) mortality throughout the course of septic shock.

Methods: In 50 consecutive mechanically ventilated septic shock patients, plasma angiopoietin-2, VWF and angiopoietin-1 levels and fluid balance, partial pressure of oxygen/inspiratory oxygen fraction and the oxygenation index as indicators of vascular permeability and pulmonary dysfunction, respectively, were measured until day 28.

Results: Angiopoietin-2 positively related to the fluid balance and pulmonary dysfunction, was higher in non-survivors than in survivors and independently predicted non-survival throughout the course of septic shock.

The interaction of soluble Tie2 with angiopoietins and pulmonary vascular permeability in septic and nonseptic critically ill patients.

Circulating angiopoietin (Ang) 1 may inhibit and Ang-2 may enhance pulmonary vascular permeability in septic and nonseptic patients with or at risk for acute lung injury or acute respiratory distress syndrome. We hypothesized that the soluble form of the Ang-binding Tie2 receptor (sTie2), whose shedding may be induced by vascular endothelial growth factor (VEGF) levels, may bind circulating Angs and thereby inhibit their effects on pulmonary vascular permeability. In 24 septic and 40 nonseptic mechanically ventilated patients, sTie2, Ang-1, Ang-2, and VEGF plasma levels were measured together with the pulmonary leak index (PLI) for (67)Gallium-labeled transferrin as a measure of pulmonary vascular permeability.

Extravascular lung water to blood volume ratios as measures of pulmonary capillary permeability in nonseptic critically ill patients.

Purpose: The aim of this study is to evaluate the value of extravascular lung water (EVLW) to intrathoracic blood volume, global end-diastolic volume, or pulmonary blood volume ratios as a reflection of pulmonary permeability in nonseptic critically ill patients with or at risk for acute lung injury/acute respiratory distress syndrome (ALI/ARDS).

Methods: Pulmonary permeability was measured by the pulmonary leak index (PLI) for (67)gallium-labeled transferrin and EVLW and blood volumes by the transpulmonary indicator dilution technique in 20 mechanically ventilated patients, before and after fluid loading, guided by changes in central venous pressure.

Results: Nine (45%) patients had ALI/ARDS according to current criteria.

Crystalloid or colloid fluid loading and pulmonary permeability, edema, and injury in septic and nonseptic critically ill patients with hypovolemia.

Objective: To compare crystalloid and colloid fluids in their effect on pulmonary edema in hypovolemic septic and nonseptic patients with or at risk for acute lung injury/acute respiratory distress syndrome. We hypothesized that 1) crystalloid loading results in more edema formation than colloid loading and 2) the differences among the types of fluid decreases at high permeability.

Design, Setting, And Patients: Prospective randomized clinical trial on the effect of fluids in 24 septic and 24 nonseptic mechanically ventilated patients with clinical hypovolemia.

The angiopoietin-Tie2 system as a therapeutic target in sepsis and acute lung injury.

Background: Sepsis and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are life-threatening syndromes characterised by inflammation and increased vascular permeability. Amongst other factors, the angiopoietin-tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (Tie2) system is involved.

Objective: To explore whether the angiopoietin-Tie2 system provides suitable targets for the treatment of sepsis and ALI/ARDS.

Rho-kinase-dependent F-actin rearrangement is involved in the inhibition of PI3-kinase/Akt during ischemia-reperfusion-induced endothelial cell apoptosis.

Activation of cytoskeleton regulator Rho-kinase during ischemia-reperfusion (I/R) plays a major role in I/R injury and apoptosis. Since Rho-kinase is a negative regulator of the pro-survival phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, we hypothesized that inhibition of Rho-kinase can prevent I/R-induced endothelial cell apoptosis by maintaining PI3-kinase/Akt activity and that protective effects of Rho-kinase inhibition are facilitated by prevention of F-actin rearrangement. Human umbilical vein endothelial cells were subjected to 1 h of simulated ischemia and 1 or 24 h of simulated reperfusion after treatment with Rho-kinase inhibitor Y-27632, PI3-kinase inhibitor wortmannin, F-actin depolymerizers cytochalasinD and latrunculinA and F-actin stabilizer jasplakinolide.