Pharmacological preconditioning with inhaled nitric oxide (NO): Organ-specific differences in the lifetime of blood and tissue NO metabolites.

Background: Endogenous nitric oxide (NO) may contribute to ischemic and anesthetic preconditioning while exogenous NO protects against ischemia-reperfusion (I/R) injury in the heart and other organs. Why those beneficial effects observed in animal models do not always translate into clinical effectiveness remains unclear. To mitigate reperfusion damage a source of NO is required.

BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression.

Inhibition of bone morphogenetic protein signal transduction prevents the medial vascular calcification associated with matrix Gla protein deficiency.

Objective: Matrix Gla protein (MGP) is reported to inhibit bone morphogenetic protein (BMP) signal transduction. MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). In this study, we investigated the contribution of BMP signal transduction to the medial calcification that develops in MGP-deficient mice.

The type I BMP receptor Alk3 is required for the induction of hepatic hepcidin gene expression by interleukin-6.

Increased IL-6 production induces, via STAT3 phosphorylation, hepatic transcription of the gene encoding the iron-regulatory hormone, hepcidin, leading to development of anemia of chronic disease (ACD). Inhibition of bone morphogenetic protein (BMP) signaling prevents the induction of hepcidin gene expression by IL-6 and ameliorates ACD. Using mice with hepatocyte-specific deficiency of Alk2 or Alk3, we sought to identify the BMP type I receptor that participates in IL-6-mediated induction of hepcidin gene expression.

Atrial natriuretic peptide is negatively regulated by microRNA-425.

Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3' untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs.

Transfusion of stored autologous blood does not alter reactive hyperemia index in healthy volunteers.

Background: Transfusion of human blood stored for more than 2 weeks is associated with increased mortality and morbidity. During storage, packed erythrocytes progressively release hemoglobin, which avidly binds nitric oxide. We hypothesized that the nitric oxide mediated hyperemic response after ischemia would be reduced after transfusion of packed erythrocytes stored for 40 days.

Soluble guanylate cyclase-α1 is required for the cardioprotective effects of inhaled nitric oxide.

Reperfusion injury limits the benefits of revascularization in the treatment of myocardial infarction (MI). Breathing nitric oxide (NO) reduces cardiac ischemia-reperfusion injury in animal models; however, the signaling pathways by which inhaled NO confers cardioprotection remain uncertain. The objective of this study was to learn whether inhaled NO reduces cardiac ischemia-reperfusion injury by activating the cGMP-generating enzyme, soluble guanylate cyclase (sGC), and to investigate whether bone marrow (BM)-derived cells participate in the sGC-mediated cardioprotective effects of inhaled NO.

Increase of oxygen consumption during a progressive decrease of ventilatory support is lower in patients failing the trial in comparison with those who succeed.

Background: The aim of this study was to test the hypothesis that, during weaning from mechanical ventilation, when the pressure support level is reduced, oxygen consumption increases more in patients unable to sustain the decrease in ventilatory assistance (weaning failure).

Methods: Patients judged eligible for weaning were enrolled. Starting from 20 cm H2O, pressure support was decreased in 4-cm H2O steps, lasting 10 min each, until 0 cm H2O; this level was kept for 1 h.

Lungs of patients with acute respiratory distress syndrome show diffuse inflammation in normally aerated regions: a [18F]-fluoro-2-deoxy-D-glucose PET/CT study.

Objective: Neutrophilic inflammation plays a key role in the pathogenesis of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Positron emission tomography (PET) with [F]-fluoro-2-deoxy-D-glucose (FDG) can be used to image cellular metabolism that, during lung inflammatory processes, likely reflects neutrophils activity. The aim of this study was to assess the magnitude and regional distribution of inflammatory metabolic activity in the lungs of patients with ALI/ARDS by PET with FDG.

An improved Boussignac device for the delivery of non-invasive CPAP: the SUPER-Boussignac.

Purpose: The purpose of this study is to describe and test a modified Boussignac system for non-invasive continuous positive airway pressure, aimed at reducing the decrease in inspiratory oxygen fraction (FiO(2)) with higher inspiratory peak flow rates.

Methods: We modified a Boussignac circuit by inserting a T-piece between the Boussignac valve and the face mask. The T-piece was connected to a reservoir balloon receiving oxygen by an independent source.