ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Irving L. Kron
John A. Kern
Curtis G. Tribble
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kaza, A. K.
Right arrow Articles by Laubach, V. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kaza, A. K.
Right arrow Articles by Laubach, V. E.
Related Collections
Right arrow Lung - other
Right arrow Lung - transplantation
Right arrowRelated Article

Ann Thorac Surg 2001;71:1645-1650
© 2001 The Society of Thoracic Surgeons

Original article: general thoracic

Retinoic acid enhances lung growth after pneumonectomy

Aditya K. Kaza, MDa, Irving L. Kron, MDa, John A. Kern, MDa, Stewart M. Long, MDa, Steven M. Fiser, MDa, Richard P. Nguyen, BSa, Curtis G. Tribble, MDa, Victor E. Laubach, PhDa

a Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia Health System, Charlottesville, Virginia, USA

Address reprint requests to Dr Laubach, Department of Surgery, University of Virginia Health System, Lane Rd, MR4, Room 3111, Charlottesville, VA 22908-1359
e-mail: vel8n{at}virginia.edu

Presented at the Forty-seventh Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 9–11, 2000.


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 
Background. We sought to identify the role of retinoic acid (RA) upon lung growth. RA has a role in perinatal lung development, and we hypothesized that exogenous RA would enhance postpneumonectomy compensatory lung growth.

Methods. Utilizing the postpneumonectomy rat model, we studied the impact of RA upon contralateral lung growth. Adult Sprague-Dawley rats were divided into three groups. Group S underwent a sham left thoracotomy, group P underwent left pneumonectomy, and group R underwent left pneumonectomy with administration of exogenous RA (0.5 µg/g/day intraperitoneally). We then quantitated right lung growth after 10 and 21 days. Lung weight and volume were expressed as a ratio to the final body weight (lung weight and volume indices, LWI and LVI). Epidermal growth factor receptor (EGFR) expression was quantitated using Western blot analysis. Cellular proliferation index (CPI) was determined using BrdU immunostaining.

Results. LWI, LVI, CPI, and EGFR expression at 21 days were significantly higher in group R versus S and P. At the 10-day interval, both LWI and LVI were significantly higher in group R versus S and P.

Conclusions. RA administration markedly enhances lung growth after pneumonectomy, as evidenced by increases in LWI, LVI, and CPI. Upregulation of EGFR expression was associated with these effects.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 
The role of retinoic acid (RA) in lung growth has been elucidated in various classic experiments. RA is a product of Vitamin A metabolism and has been shown to be essential for the normal development of lung. RA has been shown to be one of the important factors controlling fetal lung development [1]. Maternal Vitamin A stores have been shown to be essential for fetal pulmonary organogensis. Rats fed a diet deficient in Vitamin A had abnormal tracheal morphology [2]. This phenomenon was noted to be a reversible one; rats initially fed a Vitamin A-deficient diet had a reversal of the abnormal pulmonary morphology once Vitamin A was returned to their diet [3]. Massaro and Massaro [4] recently showed that treatment of newborn rats with RA influenced the postnatal formation of alveoli, and this is believed to be the first evidence of alveolar replication in the so-called terminally differentiated lungs. They also demonstrated that administration of RA caused a reversal in the pulmonary pathology of emphysematic rats [5]. Although the phenomenon of compensatory lung growth has been well described, little is known about the modulation of such growth. We have recently reported that the administration of epidermal growth factor enhances lung growth after pneumonectomy and that this correlated with an upregulation of the epidermal growth factor receptor [6]. With this background, we sought to understand the effects of RA in the process of lung growth. The rat postpneumonectomy lung growth model was used because of its reliability, reproducibility, and its establishment as a lung growth model.

Various classic experiments have shown the rapid and restorative nature of lung growth after pneumonectomy [7–10]. Our laboratory has shown that adult lungs, when transplanted into immature recipients, exhibit hyperplastic growth [11]. This growth was believed to be due to the various humoral factors in the immature recipient. The present study, through the use of RA, seeks to test our overall hypothesis that adult regenerative lung growth can be augmented beyond that which occurs in response to pneumonectomy.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 Discussion
 References
 
Animals
Adult male Sprague-Dawley rats weighing approximately 400 grams each were utilized for all experiments. Animal acquisition was under the supervision of the Department of Comparative Medicine and a licensed veterinarian. Facilities for animal care are accredited by the American Association for Accreditation of Laboratory Animal Care. The facility is approved by the Institutional Animal Care and Use Committee. All animals received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and "The Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Science and published by the National Institutes of Health (NIH publication 85-23, revised 1985).

Operative model
Rats were divided into 3 groups (S, P, and R), and each group was subdivided into 2 groups based on postoperative study time (10 or 21 days). There were 8 animals in each subgroup to allow for adequate tissue samples for molecular and morphometric analysis. All animals were anesthetized with a combination of ketamine and xylazine injected intraperitoneally followed by endotracheal intubation with a 16F gauge catheter. They were then ventilated with room air using a pressure-regulated rodent ventilator (Kent Scientific, Litchfield, CT), placed in the right lateral decubitus position, and shaved and prepped in a sterile fashion.

Animals in group S underwent a sham thoracotomy on the left side. Animals in group P underwent a left pneumonectomy. Animals in group R underwent a left pneumonectomy with the administration of exogenous retinoic acid (0.5 µg/g/day intraperitoneally, a generous gift from Hoffman-La Roche, Nutley, NJ). After the sham left thoracotomy (group S), the chest was closed after an expiratory sigh using 3-0 silk suture and skin closed using surgical staples. Animals in groups P and R underwent a posterolateral thoracotomy; the left lung was freed from the inferior pulmonary ligament. The lung was then delivered into the surgical wound, the hilum tied with a 4-0 silk ligature, and the lung excised. The chest was closed as described above. Animals were allowed to recover from surgery and extubated after initiation of spontaneous respirations. The animals then received postoperative analgesia in the form of buprenorphine injected intramuscularly every 12 hours for the first 24 hours. The animals were allowed to feed ad libitum and maintained in a controlled environment.

After the designated time interval, the animals were anesthetized, weighed, intubated via a tracheostomy, and exposure of the thoracic organs was obtained by a bilateral anterior sternothoracotomy. The animals were rapidly exsanguinated by vena caval division. The right lung in half the animals was removed, patted dry, weighed, snap frozen in liquid nitrogen, and stored at -80°C for molecular analyses. The remaining animals received intratracheal instillation of 70% ethanol to a pressure of 20 cm H2O. The right lung was then removed with the fixative in place, ligated at the hilum and stored in 70% ethanol for 24 hours. Lung volume was obtained by volume displacement technique as described by Scherle [12]. The lung volumes (mL) and lung weights (g) were expressed as a ratio to the final body weights of the animals (g) to correct for the variability in animal sizes. The lung was then paraffin embedded and random sections obtained for morphometric analysis.

Morphometry
Lung sections were H & E stained and used for morphometric analysis. Lung morphometry was carried out using the point counting technique described by Gil [13] and the three-level sampling technique described by Davies [14] and Wandel and colleagues [15]. The volumes of the various respiratory regions were determined using a 42-point test reticule (lattice with 85 µm grid lines) attached to a Nikon Eclipse E400 microscope. This technique is briefly described below. The first level of analysis, which is usually performed under gross inspection, was not performed due to the small size of the rat lung and the lack of accurate differentiation at the gross level. The second level of analysis was performed at 50x magnification. The number of lattice points that fell on intra-acinar air space and their intervening tissue was designated as Pr. Points that corresponded with extra-acinar airways and vessels less than 0.5 mm in diameter were ignored. Intra- and extra-acinar airspace refers to the areas in the lung that correspond to the space inside and outside of an alveolar unit, respectively. The volume of the respiratory region (Vvr) was calculated using the following equation:

The third level of analysis was performed at 200x magnification. The number of lattice points that overlap the respiratory airspaces was designated as Pra. The volume of the respiratory airspace (Vra) was calculated using the following equation:

The next level of analysis was also performed at 200x magnification. The number of test lines intercepting the airspace-epithelial interface was designated as Is. The alveolar surface density (Sv) was then determined using the following equation:

where d = length of the test grid line (85 µm) and Pp = total number of test points on the lung parenchyma = 42.

The relative values of the various respiratory compartments in the lung were then calculated. The total volume of respiratory region, a measure of the volume of the alveoli and the intervening tissue, was calculated as follows:

The total volume of the respiratory airspace, a measure of alveolar volume in the lung without the intervening tissue was calculated as follows:

(VL = total volume of the lung.)

Western analysis
Total lung protein (120 µg), quantitated using the Bradford method [16], was fractionated on a 7.5% (w/v) sodium dodecyl sulfate polyacrylamide gel, and transferred to nitrocellulose using an electrophoretic transfer cell (Bio-Rad, Hercules, CA). The blot was blocked and incubated with primary epidermal growth factor receptor (EGFR) antibody (1:300, Santa Cruz Biotechnology, Santa Cruz, CA) for 2 hours at room temperature, followed by washing with 50 mM Tris HCl pH 7.4, 150 mM NaCl, 0.1% Tween. The blot was then incubated for 1 hour with secondary antibody coupled to horseradish peroxidase and washed as before. Protein bands were visualized by chemiluminescence (ECL, Amersham, Arlington Heights, IL) and quantitated by computerized densitometry. Preliminary studies using A431 cell lysate, not shown, indicate that the bands on the Western blot co-migrate with the 170kDa EGFR in A431 cell lysate.

5-bromo-2'-deoxyuridine (BrdU) labeling and detection
BrdU, a thymidine analogue, is incorporated into DNA during the S phase (DNA synthesis) of the cell cycle. Cells that have incorporated BrdU can then be detected by immunohistochemistry. The percentage of stained cells can then be counted to yield the proliferation index. BrdU (50 mg/kg) was injected intraperitoneally 2 hours prior to lung harvest. For immunohistochemistry, the VectaStain ABC-AP kit (Vector Laboratories, Burlingame, CA) was utilized using anti-BrdU monoclonal antibody (1:100, Dako Corp, Carpinteria, CA). Slides were processed as instructed, counterstained with nuclear fast red, and evaluated using light microscopy. Proliferation indices were determined in peripheral lung tissue using the ratio of the number of labeled nuclei among 1,000 total counted nuclei. Endothelial cells and cells from large airways were excluded from this process. This technique allows us to calculate the percentage of alveolar cells (mostly type II pneumocytes) that exhibit cell division, thus helping determine if RA has a mitogenic effect on the lung tissue.

Statistical methodology
Measurements are reported as the mean ± standard error of the mean (SEM). Two-way analysis of variance (ANOVA) and contrast analysis were used to determine if a difference exists between study groups. A p value of 0.05 or less is used to indicate significant differences. Bonferroni multiple comparison test was used when appropriate.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 Discussion
 References
 
Changes in total body weight
The initial and final total body weight of the animals in the 3 groups at 10 and 21 days are illustrated in Figure 1. We did not notice significant difference between the initial body weight and the final body weight in any of the groups except the sham thoracotomy animals at 21 days (S21, p = 0.007).



View larger version (42K):
[in this window]
[in a new window]
  		Fig 1. Initial and final total body weight (iTBW and fTBW) at 10- and 21-day intervals. *p = 0.007 for iTBW versus fTBW. (P = pneumonectomy; R = pneumonectomy with administration of retinoic acid; S = sham thoracotomy.)

 
Lung volume index (LVI)
The results of the LVI are illustrated in Figure 2. Pneumonectomy alone significantly increased LVI at both 10 and 21 days (p < 0.001) when compared with the sham group. At 10 days, the LVI was significantly higher in the RA-treated group when compared with the sham thoracotomy and untreated pneumonectomy groups (17.68 ± 0.82 versus 10.93 ± 0.46 and 14.82 ± 0.68, p < 0.001). Similarly, at 21 days, the RA-treated group had a significantly higher LVI when compared with the sham thoracotomy and untreated pneumonectomy groups (25.27 ± 0.66 versus 10.16 ± 0.17 and 14.03 ± 0.12, p < 0.001).



View larger version (35K):
[in this window]
[in a new window]
  		Fig 2. Lung volume index at 10- and 21-day intervals. @p < 0.001 versus S10; *p < 0.001 versus S10 and P10; &p < 0.001 versus S21; #p < 0.001 versus S21 and P21. (P = pneumonectomy; R = pneumonectomy with administration of retinoic acid; S = sham thoracotomy.)

 
Lung weight index (LWI)
The results of the LWI are illustrated in Figure 3. LWI was significantly increased in the pneumonectomy group at 21 days when compared with the sham group (p < 0.001). At 10 days, the RA-treated group had a significantly higher LWI when compared with the sham thoracotomy and untreated pneumonectomy groups (3.98 ± 0.13 versus 2.81 ± 0.07 and 3.09 ± 0.11, p < 0.001). Similarly, at 21 days, the RA-treated group had a significantly higher LWI when compared with the sham thoracotomy and untreated pneumonectomy groups (4.44 ± 0.03 versus 2.37 ± 0.05 and 3.86 ± 0.03, p < 0.001).



View larger version (47K):
[in this window]
[in a new window]
  		Fig 3. Lung weight index at 10- and 21-day intervals. *p < 0.001 versus S10 and P10; @p < 0.001 versus S21; #p < 0.001 versus S21 and P21. (P = pneumonectomy; R = pneumonectomy with administration of retinoic acid; S = sham thoracotomy.)

 
Cellular proliferation index (CPI)
The lungs from animals at the 21-day interval were analyzed to determine the CPI, and the results are illustrated in Figure 4. Pneumonectomy caused a significant rise in CPI when compared with the sham group (p < 0.001). Animals that received RA had a significantly higher CPI when compared with the sham thoracotomy and untreated pneumonectomy groups (5.33 ± 0.57 versus 0.95 ± 0.06 and 3.69 ± 0.36, p < 0.001).



View larger version (21K):
[in this window]
[in a new window]
  		Fig 4. Cellular proliferation index (% of dividing cells) at 21-day interval. #p < 0.001 versus S21; *p < 0.001 versus S21 and P21. (P = pneumonectomy; R = pneumonectomy with administration of retinoic acid; S = sham thoracotomy.)

 
Epidermal growth factor receptor (EGFR) expression
Western analysis was used to measure the expression of EGFR, and the results are illustrated in Figure 5. At 10 days, the RA-treated group had a trend towards a higher expression of EGFR when compared with the sham thoracotomy and untreated pneumonectomy groups, however, this was not statistically significant (data not shown). At 21 days, the RA-treated group had a significant upregulation in EGFR when compared with the sham thoracotomy and untreated pneumonectomy groups (5.62 ± 0.73 versus 2.79 ± 0.62 and 3.36 ± 0.22, p = 0.017).



View larger version (30K):
[in this window]
[in a new window]
  		Fig 5. Western blot analysis for the detection of epidermal growth factor receptor (EGFR) at 21 days. The Western blot is shown at top (EGFR, 170kDa). The computerized densitometry is shown below. *p = 0.017 versus S21 and P21. (P = pneumonectomy; R = pneumonectomy with administration of retinoic acid; S = sham thoracotomy.)

 
Morphometric analysis
Morphometric analysis was used to determine the alveolar surface density (Sv), volume of respiratory regions (TVvr), and volume of respiratory airspaces (TVvra) in the lung. These results are shown in Table 1. At 10 days, the RA-treated group had a significantly lower Sv when compared with the sham and pneumonectomy groups. At 10 days, the treatment group had a significantly higher TVvr when compared with the other 2 groups, but TVvra in the treatment group was only higher than the sham thoracotomy group. At 21 days, there was no difference in Sv among the 3 groups, but both TVvr and TVvra were significantly higher in the RA-treated group when compared with the other 2 groups.


View this table:
[in this window]
[in a new window]
  		Table 1. Morphometric Analysis for Sham, Pneumonectomy, and Pneumonectomy Group With Exogenous RA at 10- and 21-day Intervals

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 Discussion
 References
 
RA and its precursor Vitamin A are essential for pulmonary morphogenesis. Maternal Vitamin A deficiency has been shown to result in improper fetal lung development and branching [2], and retinoids have been implicated in the development of the tracheal and bronchopulmonary structures in the lung. RA treatment stimulates type II pneumocyte proliferation in cell cultures [17], which is similar to the mitogenic response that we observed in this in vivo model. The role of RA in lung development, however, is not limited to the antenatal period, as it has been shown to induce alveolar development in the postnatal period [4]. In this study, we wanted to determine the role of RA in postpneumonectomy compensatory lung growth. Our results indicate that the administration of exogenous RA enhances contralateral lung growth after pneumonectomy beyond what occurs normally. We studied the growth response at two time points, 10 days and 21 days. The earlier time point was chosen to study molecular mediators that might be upregulated during the growth period. The later time point was chosen to study morphometric and cellular responses at the conclusion of lung growth, since it has been shown that postpneumonectomy lung growth reaches a plateau between 10 and 21 days [6]. At both time points, we noted an increase in the LWI and LVI in the RA-treated group when compared to both the sham thoracotomy group and the untreated pneumonectomy group. CPI was elevated in the RA-treated group when compared with the other 2 groups at 21 days. This growth response was associated with an upregulation of EGFR expression at the 21-day interval in the RA-treated rats. This association between RA and EGFR has been elucidated in various studies. One such study, by Schuger and colleagues [18], showed that an interaction between EGFR and RA was responsible for the effects of RA on lung development. We have recently shown that the administration of epidermal growth factor augments lung growth after pneumonectomy due to upregulation of its receptors by an auto-regulatory process [6]. Similarly, we now show that the effect of RA on postpneumonectomy lung growth is associated with the EGFR signaling pathway. Morphometric analysis revealed that the administration of RA enhances the volume of respiratory region and respiratory airways at both 10 and 21 day intervals. The alveolar surface density, however, is lower in the RA-treated group at 10 days, and returns to normal levels at 21 days. We can postulate that RA enhances lung volume in the early time point by alveolar hypertrophy, and that at the later time point the hypertrophic response is replaced by alveolar hyperplasia, which in turn restores the alveolar surface density.

Vitamin A pretreatment has been shown to lower the incidence and severity of nitrofen-induced congenital diaphragmatic hernia secondary to an enhancement of lung growth and maturation [19], which shows the efficacy of RA in the treatment of lung injury. Our study provides a novel means of modulating postpneumonectomy compensatory lung growth. A better understanding of the various key modulators of lung growth has enormous clinical application.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
Discussion
 References
 
The authors express their appreciation to Ms Kimberly Shockey, Mr Anthony Herring, Ms Sheila Hammond, and Dr Paul Davies for their invaluable technical assistance. This research was supported by National Institutes of Health grants RO1 HL48242 and T32 HL07849, and by NICHD/NIH through cooperative agreement U54 HD28934.


   Discussion
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
References
 
DR JOHN R. ROBERTS (Nashville, TN): I enjoyed your study very much. I wonder if you had a control study from your pneumonectomy group at a later date? What I am getting at is, are you postulating that the retinoic acid gets you to a baseline improvement in lung growth sooner, or that it gets you lung growth that you would not have otherwise?

DR KAZA: Thank you for the question. It has been shown in traditional studies that postpneumonectomy compensatory lung growth reaches a peak in the 2nd and 3rd week in rats. So that is basically the historical cohort that serves as a control for this experiment. Based on these experimental findings, we believe that retinoic acid enhances postpneumonectomy lung growth beyond that noted in untreated pneumonectomy animals.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 Discussion
 References
 

  1. Masuyama H., Hiramatsu Y., Kudo T. Effect of retinoids on fetal lung development in the rat. Biol Neonate 1995;67:264-273.[Medline]
  2. Wolbach S.B., Howe P.R. Tissue changes following deprivation of fat-soluble A vitamin. J Exp Med 1925;42:753-777.[Abstract]
  3. Wolbach S.B., Howe P.R. Epithelial repair in recovery from vitamin A deficiency. J Exp Med 1933;57:511-526.[Abstract]
  4. Massaro G.D., Massaro D. Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats. Am J Physiol 1996;270:L305-L310.[Abstract/Free Full Text]
  5. Massaro G.D., Massaro D. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat Med 1997;3:675-677.[Medline]
  6. Kaza A.K., Laubach V.E., Kern J.A., et al. Epidermal growth factor augments post-pneumonectomy lung growth. J Thorac Cardiovasc Surg 2000;120:916-922.[Abstract/Free Full Text]
  7. Brody J.S. Time course of and stimuli to compensatory growth of the lung after pneumonectomy. J Clin Invest 1975;56:897-904.
  8. Buhain W.J., Brody J.S. Compensatory growth of the lung following pneumonectomy. J Appl Physiol 1973;35:898-902.[Free Full Text]
  9. Cagle P.T., Thurlbeck W.M. Postpneumonectomy compensatory lung growth. Am Rev Respir Dis 1988;138:1314-1326.[Medline]
  10. Rannels D.E., Rannels S.R. Compensatory growth of the lung following partial pneumonectomy. Exp Lung Res 1988;14:157-182.[Medline]
  11. Binns O.A., DeLima N.F., Buchanan S.A., et al. Mature pulmonary lobar transplants grow in an immature environment. J Thorac Cardiovasc Surg 1997;114:186-194.[Abstract/Free Full Text]
  12. Scherle W. A simple method for volumetry of organs in quantitative stereology. Mikroskopie 1970;26:57-60.[Medline]
  13. Gil J. Models of lung disease. New York: Marcel Dekker, 1990.
  14. Davies P. Morphologic and morphometric techniques for thedetection of drug- and toxin-induced changes in lung. Pharmacol Ther 1991;50:321-336.[Medline]
  15. Wandel G., Berger L.C., Burri P.H. Morphometric analysis of adult rat lung after bilobectomy. Am Rev Respir Dis 1983;128:968-972.[Medline]
  16. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-254.[Medline]
  17. Nabeyrat E., Besnard V., Corroyer S., Cazals V., Clement A. Retinoic acid-induced proliferation of lung alveolar epithe-lial cells: relation with the IGF system. Am J Physiol 1998;275:L71-L79.[Abstract/Free Full Text]
  18. Schuger L., Varani J., Mitra R., Jr, Gilbride K. Retinoic acid stimulates mouse lung development by a mechanism involving epithelial-mesenchymal interaction and regulation of epidermal growth factor receptors. Dev Biol 1993;159:462-473.[Medline]
  19. Thebaud B., Tibboel D., Rambaud C., et al. Vitamin A decreases the incidence and severity of nitrofen-induced congenital diaphragmatic hernia in rats. Am J Physiol 1999;277:L423-L429.[Abstract/Free Full Text]

Related Article

Invited commentary
Richard N. Pierson, III
Ann. Thorac. Surg. 2001 71: 1650. [Extract] [Full Text] [PDF]



This article has been cited by other articles:


Home page
 J. Thorac. Cardiovasc. Surg.Home page
L. G. Fernandez, C. K. Mehta, I. L. Kron, and V. E. Laubach
Reinitiation of compensatory lung growth after subsequent lung resection.
J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1300 - 1305.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
A. C. Ross and N.-q. Li
Retinol Combined with Retinoic Acid Increases Retinol Uptake and Esterification in the Lungs of Young Adult Rats when Delivered by the Intramuscular as well as Oral Routes
J. Nutr., November 1, 2007; 137(11): 2371 - 2376.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. K. Sakurai, S. Lee, D. A. Arsenault, V. Nose, J. M. Wilson, J. V. Heymach, and M. Puder
Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy
Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L742 - L747.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
L. G. Fernandez, T. D. Le Cras, M. Ruiz, D. K. Glover, I. L. Kron, and V. E. Laubach
Differential vascular growth in postpneumonectomy compensatory lung growth
J. Thorac. Cardiovasc. Surg., February 1, 2007; 133(2): 309 - 316.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
M. D. Roth, J. E. Connett, J. M. D'Armiento, R. F. Foronjy, P. J. Friedman, J. G. Goldin, T. A. Louis, J. T. Mao, J. R. Muindi, G. T. O'Connor, et al.
Feasibility of retinoids for the treatment of emphysema study.
Chest, November 1, 2006; 130(5): 1334 - 1345.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
A. C. Ross, N.-q. Li, and L. Wu
The Components of VARA, a Nutrient-Metabolite Combination of Vitamin A and Retinoic Acid, Act Efficiently Together and Separately to Increase Retinyl Esters in the Lungs of Neonatal Rats
J. Nutr., November 1, 2006; 136(11): 2803 - 2807.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. Maden
Retinoids Have Differing Efficacies on Alveolar Regeneration in a Dexamethasone-Treated Mouse
Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 260 - 267.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
K. Kenzaki, S. Sakiyama, K. Kondo, M. Yoshida, Y. Kawakami, M. Takehisa, H. Takizawa, T. Miyoshi, Y. Bando, A. Tangoku, et al.
Lung regeneration: Implantation of fetal rat lung fragments into adult rat lung parenchyma
J. Thorac. Cardiovasc. Surg., May 1, 2006; 131(5): 1148 - 1153.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
E. Dikmen, M. Kara, U. Kisa, C. Atinkaya, S. Han, and U. Sakinci
Human hepatocyte growth factor levels in patients undergoing thoracic operations
Eur. Respir. J., January 1, 2006; 27(1): 73 - 76.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
X. Yan, D. J. Bellotto, D. M. Dane, R. G. Elmore, R. L. Johnson Jr., A. S. Estrera, and C. C. W. Hsia
Lack of response to all-trans retinoic acid supplementation in adult dogs following left pneumonectomy
J Appl Physiol, November 1, 2005; 99(5): 1681 - 1688.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
T. D. Le Cras, L. G. Fernandez, P. A. Pastura, and V. E. Laubach
Vascular growth and remodeling in compensatory lung growth following right lobectomy
J Appl Physiol, March 1, 2005; 98(3): 1140 - 1148.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Li, L. G. Fernandez, J. Dodd-o, J. Langer, D. Wang, and V. E. Laubach
Upregulation of Hypoxia-Induced Mitogenic Factor in Compensatory Lung Growth after Pneumonectomy
Am. J. Respir. Cell Mol. Biol., March 1, 2005; 32(3): 185 - 191.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
C. C. W. Hsia
Signals and mechanisms of compensatory lung growth
J Appl Physiol, November 1, 2004; 97(5): 1992 - 1998.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Mechanisms and Limits of Induced Postnatal Lung Growth
Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 319 - 343.
[Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
D. M. Dane, X. Yan, R. M. Tamhane, R. L. Johnson Jr., A. S. Estrera, D. C. Hogg, R. T. Hogg, and C. C. W. Hsia
Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy
J Appl Physiol, March 1, 2004; 96(3): 1090 - 1096.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Massaro and G. D. C. Massaro
Retinoids, Alveolus Formation, and Alveolar Deficiency: Clinical Implications
Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 271 - 274.
[Full Text] [PDF]

Home page
 CirculationHome page
A. K. Kaza, I. L. Kron, S. M. Leuwerke, C. G. Tribble, and V. E. Laubach
Keratinocyte Growth Factor Enhances Post-Pneumonectomy Lung Growth by Alveolar Proliferation
Circulation, September 24, 2002; 106(12_suppl_1): I-120 - I-124.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
R. Zolfaghari and A. C. Ross
Lecithin:Retinol Acyltransferase Expression Is Regulated by Dietary Vitamin A and Exogenous Retinoic Acid in the Lung of Adult Rats
J. Nutr., June 1, 2002; 132(6): 1160 - 1164.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. J. Mason
Hepatocyte Growth Factor . The Key to Alveolar Septation?
Am. J. Respir. Cell Mol. Biol., May 1, 2002; 26(5): 517 - 520.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. M. Leuwerke, A. K. Kaza, C. G. Tribble, I. L. Kron, and V. E. Laubach
Inhibition of compensatory lung growth in endothelial nitric oxide synthase-deficient mice
Am J Physiol Lung Cell Mol Physiol, June 1, 2002; 282(6): L1272 - L1278.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Irving L. Kron
John A. Kern
Curtis G. Tribble
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kaza, A. K.
Right arrow Articles by Laubach, V. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kaza, A. K.
Right arrow Articles by Laubach, V. E.
Related Collections
Right arrow Lung - other
Right arrow Lung - transplantation
Right arrowRelated Article

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS