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.

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.

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.

Control of compensatory lung growth by adrenal hormones

1987 ◽  
Vol 253 (4) ◽  
pp. E343-E348 ◽  
Author(s):  
D. E. Rannels ◽  
H. W. Karl ◽  
R. A. Bennett
Keyword(s):  
Dry Mass ◽  
Lung Mass ◽  
Lung Growth ◽  
Unoperated Control ◽  
Adrenal Hormones ◽  
Compensatory Lung Growth ◽  
The Right ◽  
Rna And Dna ◽  
Left Pneumonectomy

The effects of adrenalectomy and/or in vivo treatment with hydrocortisone acetate (HCA;5 mg X kg-1 X day-1) on lung growth were investigated in control and pneumonectomized rats of 250 g body wt. Left pneumonectomy (day 0) initiated rapid hyperplastic growth of the right lung, which was unaffected by HCA. Similarly, HCA had no effect on lung growth in unoperated control animals. Two weeks after pneumonectomy, right lung dry mass, protein, RNA, and DNA were equal to that in both lungs of unoperated rats. Adrenalectomy 5 days before (day -5) left pneumonectomy increased the rate and extent of right lung growth, but did not change its hyperplastic character. Continuous HCA treatment (days -5 to 14) prevented the adrenalectomy-mediated increase in postpneumonectomy lung growth. "Early" HCA dosing (days -5 to 6) of adrenalectomized-pneumonectomized animals suppressed lung growth to the pneumonectomy level, but from days 7 to 14 growth accelerated to the adrenalectomized-pneumonectomized rate. Conversely, "late" HCA, initiated when adrenalectomized-pneumonectomized animals had restored normal total lung mass (days 6 to 14), quickly reduced right lung growth to rates typical of unoperated controls. The latter effects were not observed unless continuous steroid treatment was provided throughout this interval. The data support a role for glucocorticosteroids in modulation of the accelerated compensatory lung growth initiated by partial resection of the tissue.

scholarly journals Methods of Delivering Mechanical Stimuli to Organ-on-a-Chip

Micromachines ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 700 ◽  
Author(s):  
Kaarj ◽  
Yoon
Keyword(s):  
Disease Modeling ◽  
Pharmaceutical Research ◽  
Experimental Medicine ◽  
Mechanical Stimuli ◽  
Physiological Models ◽  
Organ On A Chip ◽  
Flow Compression ◽  
The Right ◽  
And Behavior

Recent advances in integrating microengineering and tissue engineering have enabled the creation of promising microengineered physiological models, known as organ-on-a-chip (OOC), for experimental medicine and pharmaceutical research. OOCs have been used to recapitulate the physiologically critical features of specific human tissues and organs and their interactions. Application of chemical and mechanical stimuli is critical for tissue development and behavior, and they were also applied to OOC systems. Mechanical stimuli applied to tissues and organs are quite complex in vivo, which have not adequately recapitulated in OOCs. Due to the recent advancement of microengineering, more complicated and physiologically relevant mechanical stimuli are being introduced to OOC systems, and this is the right time to assess the published literature on this topic, especially focusing on the technical details of device design and equipment used. We first discuss the different types of mechanical stimuli applied to OOC systems: shear flow, compression, and stretch/strain. This is followed by the examples of mechanical stimuli-incorporated OOC systems. Finally, we discuss the potential OOC systems where various types of mechanical stimuli can be applied to a single OOC device, as a better, physiologically relevant recapitulation model, towards studying and evaluating experimental medicine, human disease modeling, drug development, and toxicology.

Lung volumes and distribution of regional air content determined by cine X-ray CT of pneumonectomized rabbits

1994 ◽  
Vol 76 (4) ◽  
pp. 1774-1785 ◽  
Author(s):  
L. E. Olson ◽  
E. A. Hoffman
Keyword(s):  
Lung Volume ◽  
High Speed ◽  
Body Position ◽  
Vertical Gradient ◽  
Volume Distribution ◽  
Lung Volumes ◽  
X Ray ◽  
Air Content ◽  
The Right

Lung volume, gradients in lung air content, and maximum in vivo lung dimensions were determined in rabbits in the prone, supine, and right and left lateral positions with a high-speed electron beam X-ray computed tomography scanner (Imatron C-100). Measurements were made at lung volumes corresponding to tracheal pressures of 0, 10, and 25 cmH2O. Three groups of rabbits were studied > or = 8 wk after surgery: sham-operated controls, left pneumonectomized, and left pneumonectomized with wax plombage. The magnitudes of the gradients in each direction (lung, length, width, and height) depended on lung volume and body position. The vertical gradient in air content was the largest in each group in each posture. In general, pneumonectomy did not influence the effects of the prone and supine positions on lung volume and volume distribution but did influence the effects of the right and left lateral positions on those variables. These results may be attributed to the variable effects of the mediastinal and abdominal contents on regional distending pressures.

scholarly journals Time course of carotid artery growth and remodeling in response to altered pulsatility

2010 ◽  
Vol 299 (6) ◽  
pp. H1875-H1883 ◽  
Author(s):  
John F. Eberth ◽  
Natasa Popovic ◽  
Vincent C. Gresham ◽  
Emily Wilson ◽  
Jay D. Humphrey
Keyword(s):  
Carotid Artery ◽  
Time Course ◽  
Carotid Arteries ◽  
Early Time ◽  
Mechanical Stimuli ◽  
Mean Flow ◽  
Time Courses ◽  
The Right

Elucidating early time courses of biomechanical responses by arteries to altered mechanical stimuli is paramount to understanding and eventually predicting long-term adaptations. In a previous study, we reported marked long-term (at 35–56 days) consequences of increased pulsatile hemodynamics on arterial structure and mechanics. Motivated by those findings, we focus herein on arterial responses over shorter periods (at 7, 10, and 14 days) following placement of a constrictive band on the aortic arch between the innominate and left carotid arteries of wild-type mice, which significantly increases pulsatility in the right carotid artery. We quantified hemodynamics in vivo using noninvasive ultrasound and measured wall properties and composition in vitro using biaxial mechanical testing and standard (immuno)histology. Compared with both baseline carotid arteries and left carotids after banding, right carotids after banding experienced a significant increase in both pulse pressure, which peaked at day 7, and a pulsatility index for velocity, which continued to rise over the 42-day study despite a transient increase in mean flow that peaked at day 7. Wall thickness and inner diameter also increased significantly in the right carotids, both peaking at day 14, with an associated marked early reduction in the in vivo axial stretch and a persistent decrease in smooth muscle contractility. Glycosaminoglycan content also increased within the wall, peaking at day 14, whereas increases in monocyte chemoattractant protein-1 activity and the collagen-to-elastin ratio continued to rise. These findings confirm that pulsatility is an important modulator of wall geometry, structure, and properties but reveal different early time courses for different microscopic and macroscopic metrics, presumably due to the separate degrees of influence of pressure and flow.

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.

In vivo gas trapping induced by nitrous oxide

1977 ◽  
Vol 43 (3) ◽  
pp. 414-420 ◽  
Author(s):  
R. Sergysels ◽  
R. Amyot ◽  
P. T. Macklem ◽  
R. R. Martin
Keyword(s):  
Lung Volume ◽  
Vital Capacity ◽  
Static Pressure ◽  
Gas Diffusion ◽  
Closing Volume ◽  
Inspiratory Flow Rate ◽  
Gas Trapping ◽  
The Right ◽  
Closing Pressure

Repeated vital capacity (VC) breaths in 17 anesthetized and curarized dogs induced a small but significant increase in residual volume (RV). This trapping was greatly enhanced when a mixture of 80% N2O and 20% O2 (N2O-O2) was used instead of air. VC breaths with N2O-O2 also increased closing volume, closing capacity and closing pressure determined with 133Xe. Successive quasi-static pressure volume (PV) curves of the lung showed a shift to the right at high lung volume and to the left at low lung volume. Again these changes were more impressive with N2O-O2). The PV curve of the chest wall was unchanged. Insufflations from RV were necessary to produce the gas trapping. Increase in RV was positively related to the size of the inspired volume, to N2O concentration, and inversely related to the inspiratory flow rate. Vagotomy, intravenous isoproterenol, and intravenous propanolol did not alter the phenomena. We propose that these observations can be explained by the presence of foam in the airways and that N2O leads to an increase of foam by osmotic liquid shift into the bronchioli, and/or to an increase in bubble's size by gas diffusion.

Long-term consequences of compensatory lung growth

1989 ◽  
Vol 66 (6) ◽  
pp. 2891-2894 ◽  
Author(s):  
W. M. Thurlbeck ◽  
C. Langston
Keyword(s):  
Lung Volume ◽  
Tissue Loss ◽  
Lung Growth ◽  
Lung Weight ◽  
Compensatory Lung Growth ◽  
Dna And Rna ◽  
Volume Weight ◽  
New Zealand White Rabbits ◽  
The Right

Left pneumonectomy or left nephrectomy was performed on 10-wk-old littermate male New Zealand White rabbits, and they were killed at 30 wk of age. Thirty-week-old male littermates served as controls. Nephrectomy was done to produce major tissue loss and trauma and to assess blood somatomedin C. At the end of the experiment, the right lungs of the pneumonectomy animals had a greater lung volume, weight, gas-exchanging surface area, and alveolar number than the nephrectomy animals and the controls, and their air spaces were the same size. When compared with both lungs of the nephrectomy group and the controls, lung weight was the same; lung volume, alveolar number, and protein were not significantly less in the pneumonectomy group, but gas-exchanging area (compared with controls only), DNA, and RNA were. After left nephrectomy, the right kidney increased in weight; nephrectomy had no effect on lung size or structure. We conclude that pneumonectomy at age 10 wk in male rabbits results in significant compensatory lung growth, including alveolar multiplication, and this persists to age 30 wk. Compensatory lung growth, however, was incomplete; that is, it did not reconstitute (equal) in all respects that of both lungs of the nephrectomy animals or the controls.

Recovery periods restore mechanosensitivity to dynamically loaded bone

2001 ◽  
Vol 204 (19) ◽  
pp. 3389-3399 ◽  
Author(s):  
Alexander G. Robling ◽  
David B. Burr ◽  
Charles H. Turner
Keyword(s):  
Bone Formation ◽  
Bone Cells ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Four Point Bending ◽  
Rat Tibia ◽  
Time Required ◽  
The Right

SUMMARY Bone cells are capable of sensing and responding to mechanical forces, but mechanosensitivity begins to decline soon after the stimulus is initiated. Under continued stimulation, bone is desensitized to mechanical stimuli. We sought to determine the amount of time required to restore mechanosensitivity to desensitized bone cells in vivo by manipulating the recovery time (0, 0.5, 1, 2, 4 or 8 h) allowed between four identical daily loading bouts. We also investigated the osteogenic effectiveness of shorter-term recovery periods, lasting several seconds (0.5, 3.5, 7 or 14 s), introduced between each of 36 identical daily loading cycles. Using the rat tibia four-point bending model, the right tibia of 144 adult female Sprague-Dawley rats was subjected to bending, sham bending or no loading. In the rats receiving recovery periods between loading bouts, histomorphometric measurements from the endocortical surface of the loaded and nonloaded control (left) tibiae revealed more than 100 % higher relative bone formation rates in the 8 h recovery group than in the 0 and 0.5 h recovery groups. Approximately 8 h of recovery was sufficient to restore full mechanosensitivity to the cells. In the rats allowed time to recover between load cycles, 14 s of recovery resulted in significantly higher (66–190 %) relative bone formation rates compared to any of the three shorter recovery periods. In both experiments, bone formation in the sham-bending animals was similar to that in the nonloaded control group. The results demonstrate the importance of recovery periods for (i) restoring mechanosensitivity to bone cells and (ii) maximizing the osteogenic effects of mechanical loading (exercise) regimens.

Sign in / Sign up

Export Citation Format

Share Document