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1.
J Appl Physiol (1985) ; 124(5): 1186-1193, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29357485

ABSTRACT

Chest wall strapping (CWS) induces breathing at low lung volumes but also increases parenchymal elastic recoil. In this study, we tested the hypothesis that CWS dilates airways via airway-parenchymal interdependence. In 11 subjects (6 healthy and 5 with mild to moderate COPD), pulmonary function tests and lung volumes were obtained in control (baseline) and the CWS state. Control and CWS-CT scans were obtained at 50% of control (baseline) total lung-capacity (TLC). CT lung volumes were analyzed by CT volumetry. If control and CWS-CT volumetry did not differ by more than 25%, airway dimensions were analyzed via automated airway segmentation. CWS-TLC was reduced on average to 71% of control-TLC in normal subjects and 79% of control-TLC in subjects with COPD. CWS increased expiratory airflow at 50% of control-TLC by 41% (3.50 ± 1.6 vs. 4.93 ± 1.9 l/s, P = 0.04) in normals and 316% in COPD(0.25 ± 0.05 vs 0.79 ± 0.39 l/s, P = 0.04). In 10 subjects (5 normals and 5 COPD), control and CWS-CT scans at 50% control-TLC did not differ more than 25% on CT volumetry and were included in the airway structure analysis. CWS increased the mean number of detectable airways with a diameter of ≤2 mm by 32.5% (65 ± 10 vs. 86 ± 124, P = 0.01) in normal subjects and by 79% (59 ± 19 vs. 104 ± 16, P = 0.01) in subjects with COPD. There was no difference in the number of detectable airways with diameters 2-4 mm and >4 mm in normal or in COPD subjects. In conclusion, CWS enhances the detection of small airways via automated CT airway segmentation and increases expiratory airflow in normal subjects as well as in subjects with mild to moderate COPD. NEW & NOTEWORTHY In normal and COPD subjects, chest wall strapping(CWS) increased the number of detectable small airways using automated CT airway segmentation. The concept of dysanapsis expresses the physiological variation in the geometry of the tracheobronchial tree and lung parenchyma based on development. We propose a dynamic concept to dysanapsis in which CWS leads to breathing at lower lung volumes with a corresponding increase in the size of small airways, a potentially novel, nonpharmacological treatment for COPD.


Subject(s)
Lung/physiology , Lung/physiopathology , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Ventilation/physiology , Thoracic Wall/physiology , Thoracic Wall/physiopathology , Adolescent , Adult , Aged , Bronchi/physiology , Bronchi/physiopathology , Female , Humans , Lung Volume Measurements/methods , Male , Middle Aged , Pneumonia , Respiration , Respiratory Function Tests/methods , Tidal Volume , Tomography, X-Ray Computed/methods , Total Lung Capacity/physiology , Young Adult
2.
Breathe (Sheff) ; 12(2): 159-63, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27408634

ABSTRACT

Spirometry provides clues to solving this puzzle of dyspnoea and wheeze in a young nonsmoker-the loops never lie! http://ow.ly/YC9zI A 10 s recording of expiratory sounds from this case can be found at: http://ow.ly/UVVu300moD1.

3.
J Cell Mol Med ; 15(6): 1319-28, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20629987

ABSTRACT

Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1(+)/Lin(-)/CD45(-) phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 10(6)) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL-SCs in the marrow is very low, we examined whether VSEL-SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30 min. coronary occlusion followed by reperfusion and, 48 hrs later, received an intramyocardial injection of vehicle (group I, n = 11), 1 × 10(5) enhanced green fluorescent protein (EGFP)-labelled expanded untreated VSEL-SCs (group II, n = 7), or 1 × 10(5) EGFP-labelled expanded VSEL-SCs pre-incubated in a cardiogenic medium (group III, n = 8). At 35 days after myocardial infarction (MI), mice treated with pre-incubated VSEL-SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle-treated controls. In contrast, transplantation of expanded but untreated VSEL-SCs did not produce appreciable reparative benefits. Scattered EGFP(+) cells expressing α-sarcomeric actin, platelet endothelial cell adhesion molecule (PECAM)-1, or von Willebrand factor were present in VSEL-SC-treated mice, but their numbers were very small. No tumour formation was observed. We conclude that VSEL-SCs expanded in culture retain the ability to alleviate LV dysfunction and remodelling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such pre-incubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results support the potential therapeutic utility of VSEL-SCs for cardiac repair.


Subject(s)
Cell Proliferation/drug effects , Embryonic Stem Cells , Injections, Intramuscular/methods , Myocardial Infarction/therapy , Myocardium/pathology , Stem Cell Transplantation/methods , Ventricular Function, Left , Animals , Bone Marrow/physiology , Cell Culture Techniques , Coronary Occlusion/complications , Culture Media , Cytokines/pharmacology , Disease Models, Animal , Embryonic Stem Cells/cytology , Embryonic Stem Cells/transplantation , Green Fluorescent Proteins/analysis , Intercellular Signaling Peptides and Proteins/pharmacology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myocardial Infarction/etiology , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Ventricular Remodeling
4.
Stem Cells ; 26(6): 1646-55, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18420834

ABSTRACT

Adult bone marrow (BM) contains Sca-1+/Lin-/CD45- very small embryonic-like stem cells (VSELs) that express markers of several lineages, including cardiac markers, and differentiate into cardiomyocytes in vitro. We examined whether BM-derived VSELs promote myocardial repair after a reperfused myocardial infarction (MI). Mice underwent a 30-minute coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n= 11), 1 x 10(5) Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n= 13 [cell control group]), or 1 x 10(4) Sca-1+/Lin-/CD45- EGFP-labeled cells (n= 14 [VSEL-treated group]) at 48 hours after MI. At 35 days after MI, VSEL-treated mice exhibited improved global and regional left ventricular (LV) systolic function (echocardiography) and attenuated myocyte hypertrophy in surviving tissue (histology and echocardiography) compared with vehicle-treated controls. In contrast, transplantation of Sca-1+/Lin-/CD45+ cells failed to confer any functional or structural benefits. Scattered EGFP+ myocytes and capillaries were present in the infarct region in VSEL-treated mice, but their numbers were very small. These results indicate that transplantation of a relatively small number of CD45- VSELs is sufficient to improve LV function and alleviate myocyte hypertrophy after MI, supporting the potential therapeutic utility of these cells for cardiac repair. Disclosure of potential conflicts of interest is found at the end of this article.


Subject(s)
Cardiomegaly/prevention & control , Embryonic Stem Cells/physiology , Hematopoietic Stem Cell Transplantation/methods , Myocardial Infarction/complications , Ventricular Dysfunction, Left/prevention & control , Animals , Disease Models, Animal , Embryonic Stem Cells/cytology , Flow Cytometry , Genes, Reporter , Green Fluorescent Proteins/analysis , Green Fluorescent Proteins/genetics , Male , Mice , Myocardial Infarction/pathology , Ventricular Dysfunction, Left/etiology , Ventricular Remodeling
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