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.

Effects of prior adrenalectomy on postpneumonectomy lung growth in the rat

1985 ◽  
Vol 248 (1) ◽  
pp. E70-E74 ◽  
Author(s):  
R. A. Bennett ◽  
P. C. Colony ◽  
J. L. Addison ◽  
D. E. Rannels
Keyword(s):  
Dry Mass ◽  
Hydrocortisone Acetate ◽  
Lung Growth ◽  
Sprague Dawley ◽  
Treatment Groups ◽  
Compensatory Lung Growth ◽  
Sprague Dawley Rats ◽  
Total Dna ◽  
Glucocorticoid Replacement Therapy ◽  
The Right

The effects of adrenalectomy, with and without subsequent glucocorticoid replacement therapy, on postpneumonectomy compensatory lung growth in the rat were investigated. Male Sprague-Dawley rats (200-230 g) were subjected to no operation (UNOP), left pneumonectomy (PNX), or PNX preceded by bilateral adrenalectomy 5 days earlier (ADX/PNX). At 14 days post-PNX, when compensatory lung growth is normally complete in 200-g rats, right lung (RL) dry weights of PNX (263 +/- 6 mg, n = 26) and ADX/PNX (334 +/- 13 mg, n = 25) rats were increased 58 and 101%, respectively, relative to UNOP controls (166 +/- 5 mg, n = 10). Increases in total DNA, RNA, and protein in the right lungs of PNX and ADX/PNX rats occurred in proportion to RL dry mass. The increase in all parameters examined in PNX and ADX/PNX rats at 7 days post-PNX was half that at 14 days, indicating linear lung growth in both treatment groups. The stimulatory effect of ADX on lung growth was blocked by hydrocortisone acetate (HCA), administered intraperitoneally in daily doses of 5 mg/kg, beginning on the day of PNX. The RL dry weights of HCA-treated ADX/PNX rats (241 +/- 7 mg, n = 10) did not differ significantly from the corresponding value in PNX rats (270 +/- 14 mg, n = 7). The lower RL weights in the HCA-treated rats resulted from an inhibition of cell division, as evidenced by the total RL DNA content, which was similar to that in PNX animals.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Noninvasive quantification of heterogeneous lung growth following extensive lung resection by high-resolution computed tomography

2009 ◽  
Vol 107 (5) ◽  
pp. 1569-1578 ◽  
Author(s):  
Cuneyt Yilmaz ◽  
Priya Ravikumar ◽  
D. Merrill Dane ◽  
Dennis J. Bellotto ◽  
Robert L. Johnson ◽  
...  
Keyword(s):  
Computed Tomography ◽  
High Resolution ◽  
Connective Tissue ◽  
Coefficient Of Variation ◽  
Lung Resection ◽  
Lung Growth ◽  
High Resolution Computed Tomography ◽  
Extensive Resection ◽  
Compensatory Lung Growth

To quantify the in vivo magnitude and distribution of regional compensatory lung growth following extensive lung resection, we performed high-resolution computed tomography at 15- and 30-cmH2O transpulmonary pressures and measured air and tissue (including microvascular blood) volumes within and among lobes in six adult male foxhounds, before and after balanced 65% lung resection (∼32% removed from each side). Each lobe was identified from lobar fissures. Intralobar gradients in air and tissue volumes were expressed along standardized x, y, z-coordinate axes. Fractional tissue volume (FTV) was calculated as the volume ratio of tissue/(tissue + air). Following resection compared with before, lobar air and tissue volumes increased 1.8- to 3.5-fold, and whole lung air and tissue volumes were 67 and 90% of normal, respectively. Lobar-specific compliance doubled post-resection, and whole lung-specific compliance normalized. These results are consistent with vigorous compensatory growth in all remaining lobes. Compared with pre-resection, post-resection interlobar heterogeneity of FTV, assessed from the coefficient of variation, decreased at submaximal inflation, but was unchanged at maximal inflation. The coefficient of variation of intralobar FTV gradients changed variably due to the patchy development of thickened pleura and alveolar septa, with elevated alveolar septal density and connective tissue content in posterior-caudal and peripheral regions of the remaining lobes; these areas likely experienced disproportional mechanical stress. We conclude that HRCT can noninvasively and quantitatively assess the magnitude and spatial distribution of compensatory lung growth. Following extensive resection, heterogeneous regional mechanical lung strain may exceed the level that could be sustained solely by existing connective tissue elements.

Lung volumes after an increase in lung distension in pneumonectomized ferrets

1989 ◽  
Vol 67 (4) ◽  
pp. 1418-1421 ◽  
Author(s):  
J. T. McBride
Keyword(s):  
Lung Resection ◽  
Transpulmonary Pressure ◽  
Tissue Growth ◽  
Lung Growth ◽  
Lung Volumes ◽  
Compensatory Lung Growth ◽  
Rubber Balloon ◽  
Residual Capacity ◽  
The Right

To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3–6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2–3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3–5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth.

scholarly journals Compensatory lung growth: protein, DNA and RNA lung contents in undernourished trilobectomized rats

2005 ◽  
Vol 20 (3) ◽  
pp. 219-224
Author(s):  
Raul Lopes Ruiz Júnior ◽  
Lídia Raquel de Carvalho ◽  
Antonio José Maria Cataneo
Keyword(s):  
Small Rna ◽  
Left Lung ◽  
Lung Growth ◽  
Cell Hyperplasia ◽  
Adult Rats ◽  
Compensatory Lung Growth ◽  
Dna And Rna ◽  
Male Wistar Rats ◽  
Similar Content ◽  
The Right

PURPOSE: To demonstrate compensatory lung growth (CLG) by lung contents of proteins, DNA, and RNA in undernourished young adult rats, submitted to pulmonary trilobectomy. METHODS: We used 137 male Wistar rats, randomly distributed into 9 groups; they were submitted to three treatments (control, thoracotomy, and trilobectomy), and sacrificed at three different times (7, 30, and 90 days). In trilobectomy we removed the right median, accessory, and caudal lobes. We studied lung proteins, DNA, and RNA contents. RESULTS: In the cranial lobe and left lung, protein content was higher in trilobectomized rats however there was insufficient CLG to make up for the loss. The increase of DNA in the cranial lobe and left lung of trilobectomized rats was sufficient to compensate for this loss, resulting in a similar content to controls. RNA content in trilobectomized rats, was higher in the cranial lobe and left lung, more efficient in the cranial lobe, but less than in the other groups. CONCLUSION: CLG occurred in trilobectomized rats, probably with cell hyperplasia and little hypertrophy, due to the large DNA compensation and small RNA compensation. This was markedly different to well-nourished animals, who had pronounced hypertrophy.

scholarly journals Heparin impairs angiogenic signaling and compensatory lung growth after left pneumonectomy

Angiogenesis ◽  
2018 ◽  
Vol 21 (4) ◽  
pp. 837-848 ◽  
Author(s):  
Duy T. Dao ◽  
Lorenzo Anez-Bustillos ◽  
Jared Ourieff ◽  
Amy Pan ◽  
Paul D. Mitchell ◽  
...  
Keyword(s):  
Lung Growth ◽  
Compensatory Lung Growth ◽  
Left Pneumonectomy

Lung growth in response to unilateral pneumonectomy in rapidly growing rats

1985 ◽  
Vol 248 (2) ◽  
pp. E162-E169 ◽  
Author(s):  
C. A. Watkins ◽  
L. R. Burkhart ◽  
D. E. Rannels
Keyword(s):  
Growth Response ◽  
Age Groups ◽  
Experimental Period ◽  
Lung Growth ◽  
Tissue Concentrations ◽  
Cellular Hypertrophy ◽  
Growing Rats ◽  
The Right ◽  
Noncollagen Proteins ◽  
Left Pneumonectomy

The rapidity with which lung growth is initiated and completed after pneumonectomy was examined in young rats (4 wk of age; 82 g). After left pneumonectomy, the remaining lobes of the right lung grew to equal the weight of both lungs of control animals by day 7 and within 14 days increased from 366 to 968 mg. The tissue concentrations of RNA, DNA phosphate, collagen, and noncollagen proteins did not increase during the growth response. In contrast, total amounts of these constituents increased significantly in the remaining lung of pneumonectomized animals during the 1st postoperative wk and approached levels found in both lungs of sham-operated and unoperated controls by the end of the 2nd wk after pneumonectomy. Although cell size increased in control lungs during the experimental period, there was little evidence of additional cellular hypertrophy associated with compensatory lung growth. The character of the response to pneumonectomy in these rats was similar to that observed previously in older animals (320 g). Thus in spite of the higher basal rate of lung growth in the younger rats, the pattern and rapidity of compensation after pneumonectomy was similar in both age groups.

Extensive changes in collagen synthesis and degradation during compensatory lung growth

1988 ◽  
Vol 255 (6) ◽  
pp. C754-C759 ◽  
Author(s):  
R. J. McAnulty ◽  
L. H. Staple ◽  
D. Guerreiro ◽  
G. J. Laurent
Keyword(s):  
Protein Synthesis ◽  
Collagen Synthesis ◽  
Collagen Degradation ◽  
Lung Growth ◽  
Compensatory Lung Growth ◽  
Fractional Rate ◽  
Degradation Rates ◽  
Protein Synthesis And Degradation ◽  
Synthesis And Degradation

Unilateral pneumonectomy in rats causes compensatory growth of the remaining lung. This growth involves rapid production of collagen and noncollagen proteins, but the mechanisms for these changes have not been fully investigated. Rates of collagen metabolism were measured using previously validated in vivo methods. Six days after pneumonectomy, a threefold increase in the fractional rate of collagen synthesis was observed (control 11.8 +/- 0.9%/day, pneumonectomy 30.0 +/- 4.6%/day). Collagen degradation rates also increased but returned to normal more rapidly than the synthesis rates. These changes in synthesis and degradation resulted in a 75% increase in collagen content by 28 days. Although degradation of extracellular collagens was apparently increased, the fraction degraded intracellularly decreased by approximately 30%. Noncollagen protein synthesis and degradation rates both increased by approximately 80% (control 44.3 +/- 3.4%/day, pneumonectomy 80.3 +/- 10.2%/day) with a slightly greater increase in synthesis that led to an 85% increase in noncollagen protein content 28 days after pneumonectomy. The data obtained show dramatic changes in protein synthesis and degradation during compensatory lung growth and indicate extensive remodeling of structural elements in lung tissue. The changes for intracellular collagen degradation provide further evidence that this pathway may have an important role in regulating collagen deposition.

scholarly journals Investigation of the mechanisms of VEGF-mediated compensatory lung growth: the role of the VEGF heparin-binding domain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lumeng J. Yu ◽  
Victoria H. Ko ◽  
Duy T. Dao ◽  
Jordan D. Secor ◽  
Amy Pan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Functional Outcomes ◽  
Growth Factor Receptor ◽  
Binding Domain ◽  
Heparin Binding ◽  
Lung Growth ◽  
Compensatory Lung Growth ◽  
Heparin Binding Domain ◽  
Left Pneumonectomy

AbstractMorbidity and mortality for neonates with congenital diaphragmatic hernia-associated pulmonary hypoplasia remains high. These patients may be deficient in vascular endothelial growth factor (VEGF). Our lab previously established that exogenous VEGF164 accelerates compensatory lung growth (CLG) after left pneumonectomy in a murine model. We aimed to further investigate VEGF-mediated CLG by examining the role of the heparin-binding domain (HBD). Eight-week-old, male, C57BL/6J mice underwent left pneumonectomy, followed by post-operative and daily intraperitoneal injections of equimolar VEGF164 or VEGF120, which lacks the HBD. Isovolumetric saline was used as a control. VEGF164 significantly increased lung volume, total lung capacity, and alveolarization, while VEGF120 did not. Treadmill exercise tolerance testing (TETT) demonstrated improved functional outcomes post-pneumonectomy with VEGF164 treatment. In lung protein analysis, VEGF treatment modulated downstream angiogenic signaling. Activation of epithelial growth factor receptor and pulmonary cell proliferation was also upregulated. Human microvascular lung endothelial cells (HMVEC-L) treated with VEGF demonstrated decreased potency of VEGFR2 activation with VEGF121 treatment compared to VEGF165 treatment. Taken together, these data indicate that the VEGF HBD contributes to angiogenic and proliferative signaling, is required for accelerated compensatory lung growth, and improves functional outcomes in a murine CLG model.

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