scholarly journals Separating in vivo mechanical stimuli for postpneumonectomy compensation: imaging and ultrastructural assessment

2013 ◽  
Vol 114 (8) ◽  
pp. 961-970 ◽  
Author(s):  
Priya Ravikumar ◽  
Cuneyt Yilmaz ◽  
Dennis. J. Bellotto ◽  
D. Merrill Dane ◽  
Aaron S. Estrera ◽  
...  
Keyword(s):  
Lung Volume ◽  
Ex Vivo ◽  
Left Lung ◽  
Mechanical Stimuli ◽  
Growth And Remodeling ◽  
High Resolution Computed Tomography ◽  
Surface Areas ◽  
Lung Expansion ◽  
Alveolar Tissue

Following right pneumonectomy (PNX), the remaining lung expands and its perfusion more than doubles. Tissue and microvascular mechanical stresses are putative stimuli for compensatory lung growth and remodeling, but their relative contribution remains uncertain. To temporally separate expansion- and perfusion-related stimuli, we replaced the right lung of adult dogs with a customized inflated prosthesis. Four months later, the prosthesis was either acutely deflated (DEF) or kept inflated (INF). Thoracic high-resolution computed tomography (HRCT) was performed pre- and post-PNX before and after prosthesis deflation. Lungs were fixed for morphometric analysis ∼12 mo post-PNX. The INF prosthesis prevented mediastinal shift and lateral lung expansion while allowing the remaining lung to expand 27–38% via caudal elongation, associated with reversible capillary congestion in dependent regions at low inflation and 40–60% increases in the volumes of alveolar sepal cells, matrix, and fibers. Delayed prosthesis deflation led to further significant increases in lung volume, alveolar tissue volumes, and alveolar-capillary surface areas. At postmortem, alveolar tissue volumes were 33% higher in the DEF than the INF group. Lateral expansion explains ∼65% of the total post-PNX increase in left lung volume assessed in vivo or ex vivo, ∼36% of the increase in HRCT-derived (tissue + microvascular blood) volume, ∼45% of the increase in ex vivo septal extravascular tissue volume, and 60% of the increase in gas exchange surface areas. This partition agrees with independent physiological measurements obtained in these animals. We conclude that in vivo signals related to lung expansion and perfusion contribute separately and nearly equally to post-PNX growth and remodeling.

scholarly journals Separating in vivo mechanical stimuli for postpneumonectomy compensation: physiological assessment

2013 ◽  
Vol 114 (1) ◽  
pp. 99-106 ◽  
Author(s):  
D. Merrill Dane ◽  
Cuneyt Yilmaz ◽  
Aaron S. Estrera ◽  
Connie C. W. Hsia
Keyword(s):  
Wound Healing ◽  
Lung Volume ◽  
Mechanical Stimuli ◽  
Lung Growth ◽  
Growth And Remodeling ◽  
Lung Expansion ◽  
Physiological Assessment ◽  
The Right ◽  
Sustained Increase

Following right pneumonectomy (PNX), the remaining lung expands and its perfusion doubles. Tissue and microvascular mechanical stresses are putative stimuli for initiating compensatory lung growth and remodeling, but their relative contributions to overall compensation remain uncertain. To temporally isolate the stimuli related to post-PNX lung expansion (parenchyma deformation) from those related to the sustained increase in perfusion (microvascular distention and shear), we replaced the right lung of adult dogs with a custom-shaped inflated prosthesis. Following stabilization of perfusion and wound healing 4 mo later, the prosthesis was either acutely deflated (DEF group) or kept inflated (INF group). Physiological studies were performed pre-PNX, 4 mo post-PNX (inflated prosthesis, INF1), and again 4 mo postdeflation (DEF) compared with controls with simultaneous INF prosthesis (INF2). Perfusion to the remaining lung increased ∼76–113% post-PNX (INF1 and INF2) and did not change postdeflation. Post-PNX (INF prosthesis) end-expiratory lung volume (EELV) and lung and membrane diffusing capacities (DlCO and DmCO) at a given perfusion were 25–40% below pre-PNX baseline. In the INF group EELV, DlCO and DmCO remained stable or declined slightly with time. In contrast, all of these parameters increased significantly after deflation and were 157%, 26%, and 47%, respectively, above the corresponding control values (INF2). Following delayed deflation, lung expansion accounted for 44%-48% of total post-PNX compensatory increase in exercise DlCO and peak O2 uptake; the remainder fraction is likely attributable to the increase in perfusion. Results suggest that expansion-related parenchyma mechanical stress and perfusion-related microvascular stress contribute in equal proportions to post-PNX alveolar growth and remodeling.

Comparison of postnatal lung growth and development between C3H/HeJ and C57BL/6J mice

2006 ◽  
Vol 100 (5) ◽  
pp. 1577-1583 ◽  
Author(s):  
Shawn E. Soutiere ◽  
Wayne Mitzner
Keyword(s):  
Lung Volume ◽  
Lung Development ◽  
Inbred Mice ◽  
Left Lung ◽  
Transpulmonary Pressure ◽  
Mean Linear Intercept ◽  
Old Mice

Previous work by our group has demonstrated substantial differences in lung volume and morphometric parameters between inbred mice. Specifically, adult C3H/HeJ (C3) have a 50% larger lung volume and 30% greater mean linear intercept than C57BL/6J (B6) mice. Although much of lung development occurs postnatally in rodents, it is uncertain at what age the differences between these strains become manifest. In this study, we performed quasi-static pressure-volume curves and morphometric analysis on neonatal mice. Lungs from anesthetized mice were degassed in vivo using absorption of 100% O2. Pressure-volume curves were then recorded in situ. The lungs were then fixed by instillation of Zenker’s solution at a constant transpulmonary pressure. The left lung from each animal was used for morphometric determination of mean air space chord length ( Lma). We found that the lung volume of C3 mice was substantially greater than that of B6 mice at all ages. In contrast, there was no difference in Lma (62.7 μm in C3 and 58.5 μm in B6) of 3-day-old mice. With increasing age (8 days), there was a progressive decrease in the Lma of both strains, with the magnitude of the decrease in B6 Lma mice exceeding that of C3. C3 lung volume remained 50% larger. The combination of parenchymal architectural similarity with lung air volume differences and different rates of alveolar septation support the hypothesis that lung volume and alveolar dimensions are independently regulated.

Postpneumonectomy lung expansion elicits hypoxia-inducible factor-1α signaling

2007 ◽  
Vol 293 (2) ◽  
pp. L497-L504 ◽  
Author(s):  
Quiyang Zhang ◽  
Dennis J. Bellotto ◽  
Priya Ravikumar ◽  
Orson W. Moe ◽  
Richard T. Hogg ◽  
...  
Keyword(s):  
Compensatory Growth ◽  
Nuclear Protein ◽  
Hypoxia Inducible Factor ◽  
Erythropoietin Receptor ◽  
Growth And Remodeling ◽  
Significant Elevation ◽  
Protein Levels ◽  
Lung Expansion ◽  
The Right

We ( 42 ) previously reported differential regulation of hypoxia-inducible factors (HIF-1α, -2α, and -3α) mRNA in canine lungs during normal maturation and postpneumonectomy (PNX) compensatory growth in the absence of overt hypoxia. To test the hypothesis that lung expansion activates HIF signaling, we replaced the right lung of six adult foxhounds with inflated custom-shaped silicone prosthesis to keep the mediastinum in the midline and minimize lateral expansion of the remaining lung. After 3 wk of recovery and stabilization of perfusion, the prosthesis was acutely deflated in three animals, causing the remaining lung to expand by 114%. In three other animals, the prosthesis remained inflated. Three days following deflation, we observed significant elevation in the mRNA and nuclear protein levels of HIF-1α (∼60%) as well as activation of its transcriptional regulator, the serine/threonine protein kinase B (phospho-Akt-to-total Akt ratio, 124%), and the mRNA and protein levels of its downstream targets, erythropoietin receptor (71–183%) as well as VEGF (33–58%) compared with the pre-PNX control lung from the same animal. The mRNA of HIF-2α, HIF-3α, and VEGF receptors did not change with acute deflation. We conclude that in vivo lung expansion by post-PNX deflation of space-occupying prosthesis elicits coordinated activation of HIF-1α signaling in adult lungs. This pathway could play an important role in mediating lung growth and remodeling during maturation and post-PNX compensation.

In vivo measurement of lung volumes in mice

2001 ◽  
Vol 4 (3) ◽  
pp. 215-221 ◽  
Author(s):  
W. MITZNER ◽  
R. BROWN ◽  
W. LEE
Keyword(s):  
Lung Volume ◽  
Left Lung ◽  
Steady Increase ◽  
Ct Scanner ◽  
Total Lung Volume ◽  
Functional Changes ◽  
In Vivo Measurement ◽  
Residual Capacity ◽  
Ct Density

We describe longitudinal measurements of functional residual capacity (FRC) in breathing mice using a clinical computed tomography (CT) scanner. Lungs of anesthetized mice from the A/J and C3H/HeJ strains were scanned over a 10-s period. Using a fixed threshold for CT density, we could accurately and reproducibly obtain the amount of air in the lungs at FRC, with a 10% coefficient of variation. Total lung volume, and the fractions in left and right lungs, were measured in the two strains from 4 to 12 wk of age. Results show that in both strains the FRC increases only up to 6 wk of age and then remains stable despite a steady increase in body weight. Over this time period, FRC was consistently about 50% greater in the C3H/HeJ strain compared with the A/J strain. The C3H/HeJ strain also has a significantly smaller fraction of the total lung volume in the left lung. We conclude that accurate measurements of FRC in breathing mice can be made using a standard clinical CT scanner. This method may be useful for repeated noninvasive assessment of both structural and functional changes in the lungs of experimental and genetically manipulated mice.

Developmental signals do not further accentuate nonuniform postpneumonectomy compensatory lung growth

2007 ◽  
Vol 102 (3) ◽  
pp. 1170-1177 ◽  
Author(s):  
Priya Ravikumar ◽  
Cuneyt Yilmaz ◽  
D. Merrill Dane ◽  
Robert L. Johnson ◽  
Aaron S. Estrera ◽  
...  
Keyword(s):  
Lower Lobe ◽  
Normal Lung ◽  
Lung Growth ◽  
Growth And Remodeling ◽  
High Resolution Computed Tomography ◽  
Tissue Volume ◽  
Small Vessels ◽  
Compensatory Lung Growth ◽  
Lung Expansion ◽  
Before And After

Mechanical forces imposed on lung tissue constitute major stimuli for normal lung development and postpneumonectomy (PNX) compensatory growth and remodeling. Superimposing developmental signals on PNX signals augments compensatory alveolar growth but exaggerates airway-parenchymal dissociation (i.e., dysanaptic lung growth); the latter tends to offset benefits derived from the former. In adult dogs after PNX, lobar expansion and growth of the remaining lobes were markedly non-uniform (Ravikumar et al. J Appl Physiol 97:1567–1574, 2004). We hypothesized that superimposing developmental and post-PNX signals further accentuates nonuniformity of lobar growth. We used high-resolution computed tomography (HRCT) to follow regional lung expansion and growth in foxhounds undergoing right PNX at 2.5 mo of age compared with litter-matched control (Sham) animals; scans were performed 4 and 10 mo following surgery, i.e., before and after somatic maturity. Air and tissue volumes were measured in each lobe; tissue volume estimated by HRCT includes air-free tissue and blood in small vessels <1 mm. Interlobar nonuniformity of tissue volume was absent at 4 mo but evident 10 mo after PNX; growth of the remaining left lower lobe gradually lagged behind other lobes. At maturity, nonuniformity of lobar growth in pneumonectomized puppies was similar to that previously reported in pneumonectomized adults. We conclude that superimposing developmental and post-PNX signals enhances some aspects of compensatory lung growth and remodeling without altering its nonuniform spatial distribution.

Preventing mediastinal shift after pneumonectomy impairs regenerative alveolar tissue growth

2001 ◽  
Vol 281 (5) ◽  
pp. L1279-L1287 ◽  
Author(s):  
C. C. W. Hsia ◽  
E. Y. Wu ◽  
E. Wagner ◽  
E. R. Weibel
Keyword(s):  
Left Lung ◽  
Tissue Growth ◽  
Compensatory Response ◽  
Mechanical Lung ◽  
Surface Areas ◽  
Mediastinal Shift ◽  
Lung Expansion ◽  
Capillary Blood Volume ◽  
Lung Strain ◽  
The Right

To examine the effects of mechanical lung strain on regenerative growth of alveolar septal tissue after pneumonectomy (PNX), we replaced the right lungs of adult dogs with a custom-shaped inflatable silicone prosthesis. The prosthesis was either inflated (Inf) to maintain the mediastinum at the midline or deflated to allow mediastinal shift. The animals were euthanized ∼15 mo later, and the lungs were fixed at a constant distending pressure. With the Inf prostheses, lung expansion, alveolar septal tissue volumes, surface areas, and diffusing capacity of the tissue-plasma barrier were significantly lower than with the deflated prostheses; the expected post-PNX tissue responses were impaired by 30–60%. Capillary blood volume was significantly higher with Inf prostheses, consistent with microvascular congestion. Measurements in the Inf group remained consistently and significantly higher than those expected for a normal left lung, indicating persistence of partial compensation. In one dog, delayed deflation of the prosthesis 9–10 mo after PNX led to vigorous lung expansion and septal tissue growth, particularly of type II epithelial cells. We conclude that mechanical lung strain is a major signal for regenerative lung growth; however, other signals are also implicated, accounting for a significant fraction of the compensatory response to PNX.

Differences in Transmural Pressure and Axial Loading Ex Vivo Affect Arterial Remodeling and Material Properties

2009 ◽  
Vol 131 (10) ◽  
Author(s):  
Amanda R. Lawrence ◽  
Keith J. Gooch
Keyword(s):  
Mechanical Properties ◽  
Ex Vivo ◽  
Axial Stress ◽  
Axial Loading ◽  
Transmural Pressure ◽  
Mechanical Stimuli ◽  
Axial Stretch ◽  
Mechanical Environment ◽  
Artery Geometry

Arterial axial strains, present in the in vivo environment, often become reduced due to either bypass grafting or the normal aging process. Since the prevalence of hypertension increases with aging, arteries are often exposed to both decreased axial stretch and increased transmural pressure. The combined effects of these mechanical stimuli on the mechanical properties of vessels have not previously been determined. Porcine carotid arteries were cultured for 9 days at normal and reduced axial stretch ratios in the presence of normotensive and hypertensive transmural pressures using ex vivo perfusion techniques. Measurements of the amount of axial stress were obtained through longitudinal tension tests while inflation-deflation test results were used to determine circumferential stresses and incremental moduli. Macroscopic changes in artery geometry and zero-stress state opening angles were measured. Arteries cultured ex vivo remodeled in response to the mechanical environment, resulting in changes in arterial dimensions of up to ∼25% and changes in zero-stress opening angles of up to ∼55°. While pressure primarily affected circumferential remodeling and axial stretch primarily affected axial remodeling, there were clear examples of interactions between these mechanical stimuli. Culture with hypertensive pressure, especially when coupled with reduced axial loading, resulted in a rightward shift in the pressure-diameter relationship relative to arteries cultured with normotensive pressure. The observed differences in the pressure-diameter curves for cultured arteries were due to changes in artery geometry and, in some cases, changes in the arteries’ intrinsic mechanical properties. Relative to freshly isolated arteries, arteries cultured under mechanical conditions similar to in vivo conditions were stiffer, suggesting that aspects of the ex vivo culture other than the mechanical environment also influenced changes in the arteries’ mechanical properties. These results confirm the well-known importance of transmural pressure with regard to arterial wall mechanics while highlighting additional roles for axial stretch in determining mechanical behavior.

scholarly journals Functional effect of longitudinal heterogeneity in constricted airways before and after lung expansion

2012 ◽  
Vol 112 (1) ◽  
pp. 237-245 ◽  
Author(s):  
C. Wongviriyawong ◽  
R. S. Harris ◽  
H. Zheng ◽  
M. Kone ◽  
T. Winkler ◽  
...  
Keyword(s):  
Lung Volume ◽  
Total Lung Capacity ◽  
Cross Sectional Area ◽  
Cylindrical Shape ◽  
Sectional Area ◽  
High Resolution Computed Tomography ◽  
Cross Sectional ◽  
Lung Capacity ◽  
Lung Expansion ◽  
Before And After

Heterogeneity in narrowing among individual airways is an important contributor to airway hyperresponsiveness. This paper investigates the contribution of longitudinal heterogeneity (the variability along the airway in cross-sectional area and shape) to airway resistance ( Raw). We analyzed chest high-resolution computed tomography scans of 8 asthmatic (AS) and 9 nonasthmatic (NA) subjects before and after methacholine (MCh) challenge, and after lung expansion to total lung capacity. In each subject, Raw was calculated for 35 defined central airways with >2 mm diameter. Ignoring the area variability and noncircular shape results in an underestimation of Raw (%Utotal) that was substantial in some airways (∼50%) but generally small (median <6%). The average contribution of the underestimation of Raw caused by longitudinal heterogeneity in the area (%Uarea) to %Utotal was 36%, while the rest was due to the noncircularity of the shape (%Ushape). After MCh challenge, %Uarea increased in AS and NA ( P < 0.05). A lung volume increase to TLC reduced %Utotal and %Uarea in both AS and NA ( P < 0.0001, except for %Utotal in AS with P < 0.01). Only in NA, %Ushape had a significant reduction after increasing lung volume to TLC ( P < 0.005). %Uarea was highly correlated, but not identical to the mean-normalized longitudinal heterogeneity in the cross-sectional area [CV2( A)] and %Ushape to the average eccentricity of the elliptical shape. This study demonstrates that Raw calculated assuming a cylindrical shape and derived from an average area along its length may, in some airways, substantially underestimate Raw. The observed changes in underestimations of Raw with the increase in lung volume to total lung capacity may be consistent with, and contribute in part to, the differences in effects of deep inhalations in airway function between AS and NA subjects.

Hair cell changes after cationic stimulation of corti's organ

1989 ◽  
Vol 47 ◽  
pp. 798-799
Author(s):  
Cesar D. Fermin ◽  
Hans-Peter Zenner
Keyword(s):  
Organ Of Corti ◽  
Cross Sectional ◽  
Surface Areas ◽  
High K ◽  
Anatomical Arrangement ◽  
Cell Cytosol ◽  
High Concentrations ◽  
K Concentration ◽  
Cell Changes

Contraction of outer and inner hair cells (OHC&IHC) in the Organ of Corti (OC) of the inner ear is necessary for sound transduction. Getting at HC in vivo preparations is difficult. Thus, isolated HCs have been used to study OHC properties. Even though viability has been shown in isolated (iOHC) preparations by good responses to current and cationic stimulation, the contribution of adjoining cells can not be explained with iOHC preparations. This study was undertaken to examine changes in the OHC after expossure of the OHC to high concentrations of potassium (K) and sodium (Na), by carefully immersing the OC in either artifical endolymph or perilymph. After K and Na exposure, OCs were fixed with 3% glutaraldehyde, post-fixed in osmium, separated into base, middle and apex and embedded in Araldite™. One μm thick sections were prepared for analysis with the light and E.M. Cross sectional areas were measured with Bioquant™ software.Potassium and sodium both cause isolated guinea pig OHC to contract. In vivo high K concentration may cause uncontrolled and sustained contractions that could contribute to Meniere's disease. The behavior of OHC in the vivo setting might be very different from that of iOHC. We show here changes of the cell cytosol and cisterns caused by K and Na to OHC in situs. The table below shows results from cross sectional area measurements of OHC from OC that were exposed to either K or Na. As one would expect, from the anatomical arrangement of the OC, OHC#l that are supported by rigid tissue would probably be displaced (move) less than those OHC located away from the pillar. Surprisingly, cells in the middle turn of the cochlea changed their surface areas more than those at either end of the cochlea. Moreover, changes in surface area do not seem to differ between K and Na treated OCs.

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