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The aim of the present study was to evaluate the mechanism of diastolic dysfunction (DD) after aortic valve replacement (AVR) in patients with aortic stenosis (AS).Supine bicycle exercise Doppler echocardiography (EDE) with measurement of early diastolic peak velocities of transmitral flow (E) and mitral septal annular movement (E') was performed in 38 patients with AS at least 24 months after AVR and in 19 sex- and age-matched normal controls. AS patients had a 27.4±32.7% decrease in the ratio of left ventricular (LV) mass index to LV end-diastolic volume index (LVMI/LVEDVI) after AVR. Pre-AVR E' was significantly lower in AS patients (4.3±1.6 cm/s vs. 7.7±1.6 cm/s, P0.005), resulting in a higher E/E' (16.7±5.4 vs. 9.3±1.8, P0.001). E/E' at rest did not change significantly after AVR. Both E and E' increased progressively with exercise, and the increase in E' (P0.001) but not E (P=0.675) was greater in normal controls than in AS patients (P0.001). Peak E/E'13 during EDE was more common in AS patients than in controls (89.5%, 34/39 vs. 0%, 0/19, P0.001). On multivariate analysis, LVMI/LVEDVI (Y=8.703+4.199X, r=0.433, P=0.001) was the only factor associated with peak E/E' during EDE.Persistent DD is present after AVR, due primarily to failure in normal physiologic augmentation of LV relaxation during exercise, associated with incomplete or inadequate regression of LV hypertrophy.

The aims of this study were to evaluate the three-dimensional features and geometric determinants of the vena contracta (VC) in functional tricuspid regurgitation (TR) and to identify optimal width cutoff values for assessing functional TR severity.Real-time three-dimensional full-volume and color Doppler and two-dimensional Doppler echocardiographic images were obtained in 52 patients with various degrees of functional TR and in sinus rhythm. The tricuspid valve and right ventricle were geometrically analyzed. VC widths parallel to the septal-lateral and anteroposterior directions, VC area, and effective regurgitant orifice area (EROA) using proximal isovelocity surface area methods on real-time three dimensional color Doppler images were measured.The septal-lateral VC width was 0.39 ± 0.37 cm smaller than the anteroposterior VC width (P.001). VC widths and area were strongly correlated with EROA. The optimal cutoff values for the septal-lateral VC width, anteroposterior VC width, and VC area were 0.63 cm, 0.76 cm, and 0.37 cm(2), respectively, for moderate functional TR (EROA ≥0.2 cm(2)) and were 0.84 cm, 1.26 cm, and 0.57 cm(2), respectively, for severe functional TR (EROA ≥0.4 cm(2)). Multiple linear regression analyses showed that the septal leaflet tenting angle and septal-lateral annular diameter independently determined septal-lateral VC width, while the anterior leaflet tenting angle and anteroposterior annular diameter independently determined the anteroposterior VC width.Different VC width cutoff values should be applied according to the plane of view in functional TR, because the VC cross-sectional shape is ellipsoidal with a long anteroposterior direction. VC widths are determined by annular dilation and leaflet tenting in the corresponding directions.

BACKGROUND AND OBJECTIVES Right ventricle (RV) remodeling can determine tricuspid valve (TV) geometry and the severity of functional tricuspid regurgitation (TR). SUBJECTS AND METHODS In 53 patients with various degrees of functional TR and in sinus rhythm, RV and TV geometries were analyzed using real-time 3-dimensional echocardiography, including tenting angles of 3 leaflets, septal-lateral and antero-posterior tricuspid annulus diameters and inlet RV dimensions, mid-RV septal-lateral dimension, and the distance between annulus and apex. A mid-systole frame when the TV tenting is smallest was selected for the analysis. RV end-diastolic and end-systolic volumes were measured. The severity of functional TR was determined by distal jet area. RESULTS TR distal jet area was mainly determined by septal-lateral annulus diameter (p

Background The exact pathogenic role of oxidative stress in the development of allergic airway inflammation is still largely unknown. Objective To investigate a possible link between increased pulmonary oxidative stress and the pivotal features of asthma during the mounting of an allergic inflammatory response. Methods To determine the relationship between oxidative stress and allergic inflammatory responses, we evaluated the sequential kinetics of oxidative stress in the lung, the development of airway inflammation, mucin hypersecretion, and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)–sensitized and challenged mouse with and without antioxidant. Parameters were measured at 9 points for more than 28 days, starting from the first day of OVA challenge with or without antioxidant treatment. The ratio of reduced to oxidized glutathione in the lungs and levels of intracellular reactive oxygen species (ROS) in the bronchial epithelium were serially measured. Bronchoalveolar lavage fluid cells, histopathologic features, and AHR were analyzed at the same time points. Results The reduced to oxidized glutathione ratio was reduced from immediately after OVA challenge to day 1, remained at this level until day 1, and rapidly recovered to the normal level after more than 2 days. Intracellular ROS levels in the bronchial epithelium followed similar kinetics. The inflammatory cells in bronchoalveolar lavage fluid reached a maximum of 3 days and decreased progressively thereafter. Histopathologic examination revealed that substantial airway inflammation persisted through day 28. The proportion of mucin-producing epithelial cells significantly increased after day 1, reached a maximum at day 3, and remained at this level until day 5. The AHR peaked on day 1 and normalized within 5 days. The pretreatment of antioxidant significantly reduced not only the increased ROS levels but also development of other phenotypes of asthma. Conclusion These results indicate that increased oxidative stress in the lung precedes other pivotal phenotypes of allergic airway disease, suggesting a critical role for increased oxidative stress in the induction of allergic airway inflammation.

To evaluate the impact of mitral regurgitation (MR) etiology on the accuracy of the proximal isovelocity surface area (PISA) method, we compared PISA method with conventional volumetric method in 176 patients with degenerative MR (prolapse or flail, group A) and 126 with functional MR (group B).

Mucus hypersecretion is a clinically important manifestation of chronic inflammatory airway diseases, such as asthma and Chronic obstructive pulmonary disease (COPD). Mucin production in airway epithelia is increased under conditions of oxidative stress. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 suppression is related to the development of airway inflammation and increased ROS levels. In this study, we investigated the role of SHP-1 in mucin secretion triggered by oxidative stress. Human lung mucoepidermoid H292 carcinoma cells were transfected with specific siRNA to eliminate SHP-1 gene expression. Cultured cells were treated with hydrogen peroxide (H(2)O(2)), and Mucin 5AC(MUC5AC) gene expression and mucin production were determined. Activation of p38 mitogen activated protein kinase (MAPK) in association with MUC5AC production was evaluated. N-acetylcysteine (NAC) was employed to determine whether antioxidants could block MUC5AC production. To establish the precise role of p38, mucin expression was observed after pre-treatment of SHP-1-depleted H292 cells with the p38 chemical blocker. We investigated the in vivo effects of oxidative stress on airway mucus production in SHP-1-deficient heterozygous (mev/+) mice. MUC5AC expression was enhanced in SHP-1 knockdown H292 cells exposed to H(2)O(2), compared to that in control cells. The ratio between phosphorylated and total p38 was significantly increased in SHP-1-deficient cells under oxidative stress. Pre-treatment with NAC suppressed both MUC5AC production and p38 activation. Blockage of p38 MAPK led to suppression of MUC5AC mRNA expression. Notably, mucin production was enhanced in the airway epithelia of mev/+ mice exposed to oxidative stress. Our results clearly indicate that SHP-1 plays an important role in airway mucin production through regulating oxidative stress.

PURPOSE Chlamydophila pneumoniae infection in the airways is thought to be associated with the pathogenesis of asthma, especially in non-atopic severe asthma with irreversible airway obstruction that may be related to airway remodeling. Here, we investigated whether C. pneumoniae infection enhances the secretion of critical chemical mediators for airway remodeling, such as VEGF, TGF-beta, and TIMP-1, in human bronchial epithelial cells (BECs) in a Th2-dominant microenvironment. METHODS Human bronchial epithelial cells (BEAS-2B cells) were infected with C. pneumoniae strain TW183 and cultured in both a Th1-dominant microenvironment with INF-gamma and a Th2-dominant microenvironment with IL-4 or IL-13 added to the culture medium. The VEGF, TGF-beta, and TIMP-1 levels in the culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). The activation of NF-kappaB in each experimental condition was determined using an electrophoretic mobility shift assay. RESULTS Chlamydophila pneumoniae-infected BECs showed enhanced secretion of VEGF, TGF-beta, and TIMP-1 compared with non-infected BECs. The levels of cytokines secreted from BECs were increased more when IL-13 was added to the culture medium. C. pneumoniae-infected BECs also showed increased NF-kappaB activation. CONCLUSIONS These results suggest that C. pneumoniae plays a role in the pathogenesis of airway remodeling in asthma, revealing a Th2-dominant immune response. Further studies are required to clarify the precise mechanism of C. pneumoniae infection in airway remodeling.