Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel

Increased brachial intima-media thickness is associated with circulating levels of asymmetric dimethylarginine in patients with COPD

Matthias Helmut Urban,1 Philipp Eickhoff,2 Georg-Christian Funk,1 Otto Chris Burghuber,1 Michael Wolzt,3 Arschang Valipour1 1Department of Respiratory and Critical Care Medicine, Ludwig-Boltzmann Institute for COPD and Respiratory Epidemiology, Otto Wagner Hospital, Vienna, Austria; 2Department of Obstetrics and Gynecology, St. Josef Hospital, Vienna, Austria; 3Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria Background: Chronic obstructive pulmonary disease (COPD) is associated with an increased cardiovascular risk. However, the mechanisms for this association are yet unclear. The aim of this study was to investigate the relationship between brachial intima-media thickness (B-IMT), an independent predictor of cardiovascular risk, systemic inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in patients with COPD and respective controls. Methods: The study sample consisted of 60 patients with stable COPD, free from overt cardiovascular disorders, as well as 20 smoking and 20 nonsmoking controls. Ultrasound assessment of B-IMT, spirometry, venous blood sampling for quantification of inflammatory markers and ADMA levels were carried out, and individual cardiovascular risk was calculated via the Framingham risk score. Results: Patients with COPD showed significantly higher B-IMT compared to smoking (P=0.007) and nonsmoking controls (P=0.033). COPD patients with elevated B-IMT had a twofold increased calculated 10-year risk for cardiovascular events compared to those below the recommended cutoff (P=0.002). B-IMT was significantly associated with systemic inflammation (interleukin-6 [IL-6]; r=0.365, P=0.006) and ADMA (r=0.331, P=0.013) in COPD. Multivariate linear regression revealed male sex and ADMA as independent predictors of B-IMT in this study sample. Conclusion: B-IMT is significantly increased in patients with COPD and is associated with systemic inflammation and ADMA levels. Keywords: cardiovascular risk, chronic obstructive pulmonary disease, comorbidity, subclinical atherosclerosis, biomarke

ROS-Dependent Signaling Mechanisms for Hypoxic Ca2+ Responses in Pulmonary Artery Myocytes

Hypoxic exposure causes pulmonary vasoconstriction, which serves as a critical physiologic process that ensures regional alveolar ventilation and pulmonary perfusion in the lungs, but may become an essential pathologic factor leading to pulmonary hypertension. Although the molecular mechanisms underlying hypoxic pulmonary vasoconstriction and associated pulmonary hypertension are uncertain, increasing evidence indicates that hypoxia can result in a significant increase in intracellular reactive oxygen species concentration ([ROS]i) through the mitochondrial electron-transport chain in pulmonary artery smooth muscle cells (PASMCs). The increased mitochondrial ROS subsequently activate protein kinase C-ɛ (PKCɛ) and NADPH oxidase (Nox), providing positive mechanisms that further increase [ROS]i. ROS may directly cause extracellular Ca2+ influx by inhibiting voltage-dependent K+ (KV) channels and opening of store-operated Ca2+ (SOC) channels, as well as intracellular Ca2+ release by activating ryanodine receptors (RyRs), leading to an increase in intracellular Ca2+ concentration ([Ca2+]i) and associated contraction. In concert with ROS, PKCɛ may also affect KV channels, SOC channels, and RyRs, contributing to hypoxic Ca2+ and contractile responses in PASMCs. Antioxid. Redox Signal. 11, 611–623

Predictors of right ventricular function as measured by tricuspid annular plane systolic excursion in heart failure

<p>Abstract</p> <p>Introduction</p> <p>Tricuspid Annular Plane Systolic Excursion (TAPSE) has independent prognostic value in heart failure patients but may be influenced by left ventricular (LV) ejection fraction. The present study assessed the association of TAPSE and clinical factors, global and regional LV function in 634 patients admitted for symptomatic heart failure.</p> <p>Methods & Results</p> <p>TAPSE were correlated with global and regional measures of longitudinal LV function, segmental wall motion scores and measures of diastolic LV function as measured from transthoracic echocardiography.</p> <p>LV ejection fraction, wall motion index scores, atrio-ventricular annular plane systolic excursion of the mitral annulus were significantly related to TAPSE. Septal and posterior mitral annular plane systolic excursion (β = 0.56, p < 0.0001 and β = 0.35, p = 0.0002 per mm, respectively) and non-ischemic etiology of heart failure (β = 1.3, p = 0.002) were independent predictors of TAPSE, R²= 0.28, p < 0.0001. The prognostic importance of TAPSE was not dependent of heart failure etiology or any of the other clinical factors analyzed, p_interaction= NS.</p> <p>Conclusion</p> <p>TAPSE is reduced with left ventricular dysfunction in heart failure patients, in particular with reduced septal longitudinal motion. TAPSE is decreased in patients with heart failure of ischemic etiology. However, the absolute reduction in TAPSE is small and seems to be of minor importance in the clinical utilization of TAPSE whether applied as a measure of right ventricular systolic function or as a prognostic factor.</p