Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 82: 1340-1348, 1997;
8750-7587/97 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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 Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takeda, S.
Right arrow Articles by Hsia, C. C. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takeda, S.
Right arrow Articles by Hsia, C. C. W.

Journal of Applied Physiology
Vol. 82, No. 4, pp. 1340-1348, April 1997
GAS EXCHANGE, MECHANICS, AND AIRWAYS

In vivo assessment of changes in air and tissue volumes after pneumonectomy

S. Takeda, E. Y. Wu, R. H. Epstein, A. S. Estrera, and C. C. W. Hsia

Departments of Internal Medicine, Radiology, and Surgery, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9034

ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES

ABSTRACT

Takeda, S., E. Y. Wu, R. H. Epstein, A. S. Estrera, and C. C. W. Hsia. In vivo assessment of changes in air and tissue volumes after pneumonectomy. J. Appl. Physiol. 82(4): 1340-1348, 1997.---We examined the progression and topographical distribution of postpneumonectomy volume changes in immature foxhounds undergoing right pneumonectomy (R-Pnx, n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequently raised to maturity. Volumes of lung air (Vair) and tissue (Vti) were estimated by computerized tomography (CT) scan at 7, 22, and 52 wk after surgery at a transpulmonary pressure of 20 cmH2O. Estimates of Vti by CT scan included both septal tissue as well as nonseptal tissue (small- and medium-sized airways and blood vessels); these were compared with estimates of septal Vti by an acetylene rebreathing (Rb) method. We found significant correlations between these techniques (VairCT = 0.83 VairRb + 275, R = 0.97; VtiCT = 1.62 VtiRb - 30, R = 0.81). Extravascular septal Vti returned to normal 7 wk after R-Pnx and remained normal up to maturity. Nonseptal Vti remained significantly below normal. The greatest increase in Vti occurred in the midlung region just cephalad and caudal to the heart. After an early period of accelerated tissue growth after R-Pnx, the rate of septal tissue growth matched that of somatic growth, whereas nonseptal tissue growth lagged behind. Compensatory growth of the remaining left lung was not associated with selective alterations in thoracic development.

lung air volume; septal lung tissue volume; acetylene rebreathing technique; computerized tomographic scan; compensatory lung growth

INTRODUCTION

AFTER MAJOR LUNG RESECTION, volume of the remaining lung increases significantly (1, 6, 14, 24). This increase is acutely due to overexpansion of existing alveoli but may also be associated chronically with growth of new alveolar tissue (5, 10, 22). Increase in lung volume (VL) by either mechanism is an important source of functional compensation in gas exchange (9, 10). If simple overdistension of existing alveoli occurs after pneumonectomy, air volume (Vair) of the remaining lung should increase while tissue volume (Vti) remains unchanged. The ratio of Vti/Vair should decrease compared with that in the corresponding lung of controls. If compensatory addition of new lung tissue occurs, Vair and Vti should increase proportionately, and the ratio of Vti/Vair should be normal. There has been no study that followed these volume changes or their topographical distribution in vivo. It is also unclear how these compensatory volume changes interact with normal thoracopulmonary growth during the period of somatic maturation.

In the present study, we took advantage of the difference in estimates of lung Vti by computerized tomography (CT) scan and by an acetylene rebreathing (Rb) technique. Lung Vti estimated by CT scan (VtiCT) includes the volume of all septal (Vtisept) and nonseptal tissues (Vtinonsept), plus the volume of blood contained in small- and medium-sized blood vessels as well as alveolar capillaries. In contrast, lung Vti estimated by the acetylene Rb technique (VtiRb) includes only the Vtisept and capillary blood (Vc) that participates in gas exchange and hence equilibrates rapidly with inspired acetylene. Our objectives were to utilize these two noninvasive techniques to determine 1) the temporal progression and topographical distribution of Vair and Vti of the lung and 2) the relative changes in Vtisept and Vtinonsept during the period of somatic maturation in immature dogs after right pneumonectomy (R-Pnx).

In addition, distortion of the thorax occurs after pneumonectomy. On chest radiographs taken previously in dogs after R-Pnx, the right hemithorax appears smaller, whereas the left hemithorax appears larger than before pneumonectomy, suggesting that compensatory inflation and/or growth of the remaining left lung may exert an expanding force on the left rib cage. A second objective of this study, therefore, was to examine whether early R-Pnx in immature animals results in distortion of volume distribution between the two hemithoraxes.

MATERIALS AND METHODS

Experimental groups. All procedures were approved by the Institutional Review Board for Animal Research. Litter-matched male purebred foxhounds were obtained from commercial breeders and underwent either R-Pnx (n = 6) or right thoracotomy without pneumonectomy (Sham; n = 6) under isoflurane anesthesia at 2 mo of age. In the R-Pnx group, a right lateral thoracotomy was made in the fifth intercostal space; the right main pulmonary artery and veins were isolated and doubly ligated. The right main bronchus was then divided and closed with staples. Air leakage was checked by immersing the bronchial stump in warm saline. After hemostasis was confirmed, the thorax was closed in three layers, and residual air in the right thorax was aspirated by a syringe. Dogs in the Sham group underwent right thoracotomy in the same fashion; the pleural space was opened and closed without pneumonectomy. One animal in the R-Pnx group died in the postoperative period because of the development of pulmonary edema. All other animals survived and were studied serially until reaching adulthood.

Measurements by CT scan. CT scan was performed under pentobarbital sodium anesthesia (25 mg/kg iv) at 7, 22, and 52 wk after surgery. Animals were intubated with a cuffed endotracheal tube, ventilated with a Harvard respirator at a tidal volume of 15 ml/kg, and placed in the supine position on the CT table. Before each image, the dog was hyperventilated to prevent spontaneous breathing during the period of imaging. Then the dog was disconnected from the respirator and allowed to exhale to functional residual capacity (FRC). The lungs were then inflated with a calibrated syringe at a volume previously determined to yield a transpulmonary pressure (Ptp) of 20 cmH2O. By using a rapid scanner (Toshiba TCT 900S), a scout film was obtained to determine anatomic landmarks. Consecutive transverse tomographic images were obtained at 5-mm intervals between the apex and the costophrenic angle. The contours of the right and left lung in each image were traced separately, and the areas were measured by using software provided by the manufacturer. Major hilar blood vessels and main stem bronchi were excluded from measurement. An average CT number for each lung field was established. During calibration, the CT number of water was set at 0 and of air at -1,000 (mean value of intratracheal air was -990 to -1,030). Total VL was estimated by numerical integration of volumes from all images by using the trapezoidal rule similar to that described previously (14, 15). Assuming that lung tissue had a CT number equal to that of muscle in the same dog (i.e., 52-59), relative contributions of tissue (Vti) and air (Vair) to the VL were computed
Vair = V<SC>l</SC> <FR><NU>CT no. of tissue − CT no. of lung</NU><DE>CT no. of tissue − CT no. of air</DE></FR>
Vti = V<SC>l</SC> − Vair
Estimates of VtiCT include the Vtisept, i.e., including capillary blood, as well as Vtinonsept, i.e., conducting airways and blood vessels.
Vti<SUB>CT</SUB> = Vti<SUB>sept</SUB> + Vti<SUB>nonsept</SUB>
To determine the topographical volume distribution in the cranial-caudal direction, VLCT, VairCT, and VtiCT corresponding to a given thoracic vertebra level (from T1 to T13) were computed at each time point after surgery.

On each CT image, the thorax was divided into left and right halves by a line drawn from the sternum to the vertebra. Areas of the each hemithorax were measured separately, and the volume of each hemithorax was calculated by the same method as given above.

Measurements by the Rb technique. Physiological estimates of lung Vair and Vti were also obtained at similar time points after surgery in the supine posture by a Rb technique previously described by this laboratory (3, 11, 14). Dogs were anesthetized by pentobarbital sodium. Esophageal and mouth pressures were recorded continuously. Gas concentrations were monitored at the mouth by a mass spectrometer. The Rb gas mixtures contained 9% helium, 0.6% acetylene, 0.3% C18O, and either 30% O2 in balance of N2 or 90% O2. After the dog was hyperventilated to prevent spontaneous breathing, it was allowed to exhale to FRC, and a preselected volume (15, 30, 45, 60, and 75 ml/kg) of Rb gas was delivered via the endotracheal tube by a calibrated syringe. The dog rebreathed this gas mixture at 30 breaths/min over 15 s, and it was delivered manually and synchronized to a metronome. The last breath was held for 10 s, and the mean Ptp was recorded during the last 2 s of breath holding. Total system volume (Vair + apparatus dead space of 55 ml) was estimated from helium dilution. Duplicate measurements were obtained at each VL. All volumes were expressed in BTPS conditions. From the pressure-volume relationship of each dog, Vair corresponding to a Ptp of 20 cmH2O was estimated by interpolation.

The volume of fine septal tissue and capillary blood that equilibrates rapidly with acetylene (Vtisept) was estimated from the intercept of the logarithmic disappearance of end-tidal acetylene with respect to helium concentration during Rb. The C18O disappearance curve was used to adjust zero time. Vc was estimated from lung diffusing capacity (DLCO) measured at two levels of alveolar O2 tensions, as described previously (12). Only the log linear portion of the end-tidal acetylene and C18O disappearance curves was utilized in this analysis. The first three breaths and breaths beyond 12 s of Rb were routinely discarded. Extravascular Vtisept was estimated by subtracting Vc from Vtisept measured by Rb (Vtisept - Vc).

Statistics. Data were normalized for body weight and expressed as means ± SE. Vair and Vti measured by CT scan at 7, 22, and 52 wk were compared with corresponding values estimated by the Rb technique by linear least-squares regression. At each time point, data from the R-Pnx and Sham groups were compared by one-way analysis of variance (ANOVA). Serial measurements and topographical distributions of VL and thoracic volume were compared between groups by repeated measures ANOVA (StatView v. 4.0, Abacus Concepts). Measurements between left and right hemithoraxes on each image were compared by paired t-test. Differences are regarded as significant if P < 0.05.

RESULTS

There were no significant differences in body weight between groups at all time points: 16.2 ± 2.4, 29.8 ± 2.2, and 31.2 ± 1.2 kg for R-Pnx group; 16.5 ± 1.5, 29.7 ± 2.7, and 31.9 ± 2.3 kg for Sham group at 7, 22, and 52 wk, respectively (means ± SE). On average, the Vair and Vti of the left lung estimated by CT scan constituted 42 ± 1% (SE) of total volume in Sham group animals. The typical anatomic changes are illustrated in one CT image from a dog 52 wk after pneumonectomy (Fig. 1). Figure 2 shows the linear correlations of lung Vair and Vti measured by CT scan and by the Rb technique for all dogs. Two outlier points >3 SD below the mean were omitted. There were strong correlations for both relationships. The relationship for lung Vair was slightly but significantly below unity (Fig. 2A). VtiCT was consistently higher than VtiRb (Fig. 2B).

Fig. 1. Typical computerized tomography (CT) image from 1 dog 52 wk after right pneumonectomy (R-Pnx) showing displacement of mediastinum, expansion of remaining lung across midline, and distortion of thoracic cage.
[View Larger Version of this Image (133K GIF file)]

Fig. 2. Correlation of lung air volumes (Vair; A) and tissue volumes (Vti; B) measured by CT scan (VairCT) and rebreathing (VairRb) ± 95% confidence intervals for mean. Lung Vti by CT scan (VtiCT) are consistently higher by CT scan than by rebreathing (VtiRb). A: VairCT = 0.83 VairRb + 275; R = 0.97; P < 0.001. B: VtiCT = 1.62 VtiRb - 30; R = 0.81; P < 0.0001.
[View Larger Version of this Image (14K GIF file)]

Figure 3 shows the progression of total Vair at Ptp = 20 cmH2O measured by CT or Rb at the three time points in each group. As measured by CT scan, Vair was significantly (P < 0.05) lower in dogs after R-Pnx than in control animals. As measured by Rb, Vair was not significantly different between groups; this is because differences in Vair become exaggerated with lung inflation. As shown by previously published data from these same dogs, FRC was similar between groups, but at a Ptp of 30 cmH2O VL was significantly lower in dogs after R-Pnx than in Sham animals (21). At 20 cmH2O, the difference is intermediate. Figure 4 compares VtiCT between groups; this estimate includes Vtisept, Vtinonsept, and Vc. In the R-Pnx group, VtiCT was lower than in controls and decreased further between 7 and 22 wk after surgery. Estimates of Vc at different times were similar between groups and were published previously (21). Figure 5 shows the partition of Vti into septal and nonseptal components at different times. There was no significant difference between groups in extravascular Vtisept (Fig. 5A). Vtinonsept was only slightly lower than in controls at 7 wk but declined with time and was significantly lower in the R-Pnx group (30% of control values) at maturity (Fig. 5B). Figure 6 shows the ratios Vtisept/Vair and Vtinonsept/Vair during maturation. There were no significant differences in Vtisept/Vair between groups, but the ratio of Vtinonsept/Vair became significantly lower in the R-Pnx group with time, indicating that growth of nonseptal tissue did not keep pace with increasing VL. Table 1 summarizes the final VL measured at maturity (~14 mo of age).

Fig. 3. By CT scan, total lung Vair at 20 cmH2O transpulmonary pressure (Ptp) was significantly lower (P < 0.05) in dogs after R-Pnx than in sham-operated animals. By Rb technique, total lung Vair at same Ptp was not significantly different between groups.
[View Larger Version of this Image (21K GIF file)]

Fig. 4. Total lung Vti, including volume of septal tissue, nonseptal tissue, and capillary blood, was significantly lower (P < 0.001) in dogs after R-Pnx than in control dogs (Sham).
[View Larger Version of this Image (15K GIF file)]

Fig. 5. Extravascular septal Vti was not significantly different between groups (A). Nonseptal Vti was significantly lower (P < 0.01) in dogs after R-Pnx than in control dogs at 22 and 52 weeks (B).
[View Larger Version of this Image (12K GIF file)]

Fig. 6. Ratio of extravascular septal tissue to Vair was not significantly different between groups. Ratio of nonseptal tissue to Vair was significantly lower in dogs after R-Pnx than in control dogs (P < 0.05). Vair was measured by Rb.
[View Larger Version of this Image (25K GIF file)]

Table 1. Lung volumes 1 yr after surgery

R-Pnx Sham P Value
No. of animals 5 6
Body weight, kg 31.2 ± 1.2  31.9 ± 2.3  0.81
Rebreathing
Vair
  Left lung* 81.9 ± 6.7  42.0 ± 2.8  <0.005
  Total lung 81.9 ± 6.7  100.1 ± 6.7  0.09
Vtisept
  Left lung* 8.20 ± 0.44  3.63 ± 0.24  <0.0001
  Total lung 8.20 ± 0.44  8.64 ± 0.57  0.56
CT scan
Vair
  Left lung 70.5 ± 5.3  40.2 ± 3.3  <0.01
  Total lung 70.5 ± 5.3  95.3 ± 6.5  <0.05
Vtitotal
  Left lung 10.11 ± 0.25  5.96 ± 0.22  <0.0001
  Total lung 10.11 ± 0.25  14.60 ± 0.57  <0.0001
CT-rebreathing
Vtinonsept
  Left lung 1.92 ± 0.40  2.33 ± 0.18  0.34
  Total lung 1.92 ± 0.40  5.96 ± 0.31  <0.0001
Values are means ± SE. All volumes are in ml/kg. Vair, lung air volume; Vtisept, septal lung tissue volume; Vtinonsept, nonseptal lung tissue volume; R-Pnx, right pneumonectomy; CT, computerized tomography; Vtitotal, total tissue volume. * Left lung volume is calculated as 42% of total volume.

As measured by CT scan, the cranial-caudal distributions of VL and Vti at each thoracic vertebral level at each time point are shown in Figs. 7 and 8, respectively. Data from Sham animals are shown for both lungs and for the left lung alone. The positions of the heart and great vessels approximately correspond to vertebral levels 6 to 9. The distributions of VL were similar among the three time points. VL in the R-Pnx animal was lower than in both lungs of the Sham animal at each vertebral level. At 7 wk after R-Pnx, the distribution of total Vti was similar to that in both lungs of Sham animals. However, as the animal matured, total Vti became significantly lower than in controls, particularly at the mid- and lower lung zones. Figure 9 shows the relative increases of VL and Vti in the R-Pnx group, expressed as a percentage of corresponding values in the left lung of Sham animals. The initial accelerated increase of Vti at 7 wk after R-Pnx was particularly marked in the midlung region, being greatest just above and below the heart. Subsequently, Vti increased proportionally to Vair, and the distributions of these were similar between groups. There were significant regional variations in the extent of Vair compensation. The greatest relative volume expansion occurred in the regions immediately cephalad and caudal to the level of the heart.

Fig. 7. Topographical distribution of total lung volume (air + tissue) measured by CT scan at given thoracic vertebra level at 7, 22, and 52 wk after surgery (A, B, and C, respectively). Values are means ± SE. Volume distribution of left lung in R-Pnx animals was significantly different from that in both lungs of Sham animals (* P < 0.05) and significantly different from that in left lung of Sham animals [§ P < 0.05 and §§§ P < 0.001, by repeated-measures analysis of variance (ANOVA)].
[View Larger Version of this Image (18K GIF file)]

Fig. 8. Topographical distribution of lung Vti measured by CT scan at a given thoracic vertebra level at 7, 22, and 52 wk after surgery. A: at 7 wk, Vti distribution of R-Pnx animals was not significantly different from that in both lungs of Sham animals. At 22 wk (B) and 52 wk (C), volume distribution was significantly different (* P < 0.01) from that in both lungs of Sham animals. At all vertebral levels, volume of left lung was persistently greater in R-Pnx animals than in corresponding left lung of Sham animals (§§ P < 0.001; §§§ P < 0.001). Values are means ± SE.
[View Larger Version of this Image (17K GIF file)]

Fig. 9. Topographical distribution of relative Vair and Vti measured by CT scan in left lung of R-Pnx dogs at 7 wk (A), 22 wk (B), and 52 wk (C) after surgery. Data are expressed as %ratio of R-Pnx-to-Sham animals' left lung. For both Vair and Vti at all 3 time points, P < 0.0001 for thoracic vertebral levels by repeated-measures ANOVA.
[View Larger Version of this Image (15K GIF file)]

Volumes of the left and right hemithorax measured at 52 wk after surgery are shown in Table 2. Volume of each hemithorax and total thoracic volume were significantly smaller in the R-Pnx group compared with the corresponding hemithorax in the Sham group. In addition, the right hemithorax was smaller than the left in both groups; the difference was statistically significant in the R-Pnx group but not in the Sham group. The distribution of thoracic volume is shown in Fig. 10. In both groups, the left hemithorax was significantly larger than the right in most images, regardless of anatomic level. Compared with the corresponding thorax in Sham animals, thoracic volume in animals after R-Pnx was lower at all anatomic levels.

Table 2. Thoracic volume measured by CT scan

R-Pnx Sham P Value, R-Pnx vs. Sham, ANOVA
Total volume 154.4 ± 4.3  187.3 ± 8.7  <0.05
Left hemithorax 79.8 ± 1.7  95.9 ± 5.6  <0.05
Right hemithorax 74.6 ± 2.9  91.4 ± 3.3  <0.005
P value, left vs. right hemithorax, paired t-test <0.05 0.16
Values are means ± SE; all volumes are in ml/kg. ANOVA, analysis of variance.

Fig. 10. Cranial-caudal distribution of volume of each hemithorax (A) and total thorax (B) at 52 wk after surgery. In both groups, P < 0.05 for left vs. right hemithorax by paired t-test. In R-Pnx group, P < 0.01 vs. corresponding Sham lung by repeated-measures ANOVA.
[View Larger Version of this Image (18K GIF file)]

DISCUSSION

Critique of methods. We found a strong correlation in lung gas volume estimated by CT scan and a Rb method. On average, VairCT was lower than VairRb by ~9%. These results differ from the reports of Hyde et al. (13) and Wandtke et al. (23), who found that gas volume at FRC calculated by CT scan underestimated FRC measured by Rb helium by 18 to 34% in dogs. This underestimation was attributed to a large extent to inaccuracies in CT measurement, e.g., boundary delineation, partial volume effect, beaming hardening, and sampling limitations, all of which can be expected to become exaggerated by a lower VL. On the other hand, our CT measurements were obtained at an inflating pressure of 20 cmH2O, which corresponds to a lung gas volume more than twice that measured at FRC. At the higher VL, contrast between lung and the surrounding tissue is enhanced; technical errors associated with CT measurement should be minimized. This methodological difference probably explains the closer agreement between CT and Rb measurements of lung gas volume in the present study. Estimates of total lung VtiCT in our Sham animals at maturity were 14.6 ml/kg, slightly smaller than the 17 ml/kg reported by Hyde et al. (13) and 18 ml/kg by Johnson et al. (14).

There is a strong correlation between lung Vtisept measured by the acetylene Rb technique and Vtisept measured at postmortem by morphometric techniques (14). The average VtiRb in our Sham animals at maturity was 8.6 ml/kg, slightly lower than the values obtained by Peterson et al. (12 ml/kg; Ref. 20) and Crapo et al. (~11.5 ml/kg; Ref. 4) but similar to that of Hyde et al. (9.0 ml/kg; Ref. 13). Lung Vti measured by CT scan is consistently higher than that by Rb acetylene by ~50%. This discrepancy is because of the inclusion of lung Vtinonsept in the CT estimates and has also been reported previously in both normal and pneumonectomized beagles (14, 15).

Compensatory lung growth: septal vs. nonseptal tissue. In immature dogs after left pneumonectomy (L-Pnx), the remaining lung was shown to undergo an early compensatory increase in the rate of alveolar growth, resulting in an increased alveolar number and VL (22). However, that study was terminated before maturity was reached. The only previous long-term study in immature dogs, by Davies et al. (5), questioned whether the acceleration of alveolar growth seen early after pneumonectomy would persist until maturity. In the present group of dogs, separate studies show that this increased rate of alveolar growth persists (21); DLCO increased nearly twofold within 4-8 wk after R-Pnx and continued to increase at a normal developmental rate until maturation. This enhanced growth of the remaining lung yielded a DLCO equivalent to that measured in two lungs of control dogs at maturity. On the other hand, VL at a given distending pressure and lung compliance remained persistently lower and resistance to air flow remained higher than normal. These mechanical abnormalities suggest either that growth of the airway lags behind that of lung parenchyma (dysanapsis) or that there had been compositional change in the connective tissue matrix to cause both an increase in viscous tissue resistance and restriction of lung expansion.

Previous reports by other investigators suggest that postpneumonectomy compensatory growth of alveolar septal tissue is more extensive than that of nonseptal tissue (conducting airways and blood vessels). Such evidence has been inferred from a lower maximal expiratory flow rate in dogs after L-Pnx (7, 8, 18) and a lower-than-expected airway cross-sectional area (17) as well as lengthening of peripheral airways (16) as seen in postmortem examination of immature ferrets after R-Pnx. Although these reports support the occurrence of dysanapsis, dysanaptic compensatory lung growth is not the only possible explanation. These findings are also consistent with a loss of radial traction on the small airways related to the reduction of elastic recoil of the remaining lung after pneumonectomy. The only data on airway and parenchymal tissue volume after pneumonectomy are from Burri and Sehovic (2), who found a less-than-expected increase in total airway tissue volume in rats after bilobectomy. The present report demonstrates for the first time the divergent responses of septal and nonseptal tissue during the period of maturation in a large animal model. We found a complete restoration of normal Vtisept after R-Pnx, consistent with previous studies in immature dogs after L-Pnx, in which the amount of lung resected is smaller (14, 22). This vigorous acceleration of septal tissue growth occurred within 7 wk after pneumonectomy; during this period, the increase in Vti exceeded the increase in Vair. Subsequently, Vtisept and lung Vair continued to increase at a matched developmental rate until maturity. These data support and extend the previous short-term findings of Thurlbeck et al. (22). On the other hand, although there was an early increase in the Vtinonsept after R-Pnx, subsequently the rate of its increase failed to match that of developmental growth. At maturity, Vtinonsept in dogs after pneumonectomy was only 30% of that in two normal lungs.

Topographical distribution of VL and thoracic volume. Using cine X-ray CT scan, Olson and Hoffman (19) found in studies of adult rabbits that the topographical distribution of air content of the lung was influenced by VL as well as by the gravitational effect of the mediastinum and abdominal content in different postures. Pneumonectomy did not significantly alter these distributions in the supine or prone position. In this study, we found that the increase in Vair and Vti of the left lung after R-Pnx occurred at all anatomic levels, but the relative increase in Vti was most pronounced in the regions just cranial and caudal to the heart and least pronounced in the apex and the costophrenic angles. Thus compensatory growth occurs most markedly in the midregion of the lung.

Johnson et al. (14) previously found, in studies of beagles that received L-Pnx as puppies, that thoracic compliance above FRC increased above that in control animals. Dimensions of the thorax measured by CT scan diminished commensurate with a reduced VL at any given Ptp. From plain chest X-rays taken previously of dogs and human subjects studied after pneumonectomy, we had observed that, although the hemithorax on the side of resection appeared smaller, as expected, the hemithorax on the side of the remaining lung often appeared larger than before pneumonectomy. However, conclusions cannot be drawn from such observations, because the entire thoracic cage, including the spine, is variably distorted by pneumonectomy. We wondered whether growth and expansion of the remaining lung, in addition to causing displacement of the mediastinum across the midline, also caused expansion of the ipsilateral rib cage. If so, after R-Pnx the volume of the right hemithorax should be smaller than control values while volume of the left hemithorax should exceed control values. Measurements of hemithoracic volumes from serial CT images show that this is not the case. The reduction of thoracic volume after R-Pnx was similarly distributed in the cranial-caudal direction. After R-Pnx, both left and right hemithoraxes were significantly smaller than the corresponding hemithorax in control animals, i.e., there was no evidence of greater expansion and growth of the left rib cage. In both groups, the left hemithorax was slightly larger (by 5-7%) than the right by paired analysis. This finding is unexpected and raises the possibility that early thoracotomy may have adversely affected subsequent development of the right rib cage in both groups. This issue cannot be resolved by the present study because of a lack of matched, unoperated dogs.

In conclusion, in this study we compared two noninvasive, in vivo techniques of estimating lung Vair and Vti in immature dogs raised to maturity after R-Pnx. Total lung Vti was restored during an initial phase of accelerated compensatory lung growth, followed by a normal rate of developmental growth that persisted until maturity. Compensatory growth involved mainly septal lung tissue, with very limited growth of nonseptal lung tissue. The disparity between Vtisept and Vtinonsept persisted throughout maturation. Early R-Pnx was not associated with a selective alteration in thoracic development.

ACKNOWLEDGEMENTS

We thank David Treakle, Stacey Arnold, and the staff of the Animal Resource Center for their technical assistance and excellent care of the animals. We also thank Robert Crawford for his assistance with CT scanning and analysis.

FOOTNOTES

   Parts of this work have been published in abstract form (S. Takeda, E. Y. Wu, M. Ramanathan and C. C. W. Hsia. Am. J. Respir. Crit. Care Med. 149: A787, 1994).

   This project was supported by National Heart, Lung, and Blood Institute (NHLBI) Grant HL-45716. S. Takeda was supported by the Will Rogers Memorial Foundation. E. Y. Wu was supported by NHLBI Training Grant TL-07362. This work was done during the tenure of C. C. W. Hsia as an established investigator of the American Heart Association.

   Present address of S. Takeda: First Dept. of Surgery, Osaka University Medical School, 202 Yamadaoka, Suita, Osaka 565, Japan.

Address for reprint requests: C. C. W. Hsia, Dept. of Internal Medicine, Univ. of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9034.

Received 22 August 1996; accepted in final form 13 November 1996.

REFERENCES

1. Arnup, M. E., H. W. Greville, L. Oppenheimer, S. N. Mink, and N. R. Anthonisen. Dynamic lung function in dogs with compensatory lung growth. J. Appl. Physiol. 57: 1569-1576, 1984. [Abstract/Free Full Text] .
2. Burri, P. H., and S. Sehovic. The adaptive response of the rat lung after bilobectomy. Am. Rev. Respir. Dis. 119: 769-777, 1979. [Medline] .
3. Carlin, J. I., C. C. W. Hsia, S. S. Cassidy, M. Ramanathan, P. S. Clifford, and R. L. Johnson, Jr. Recruitment of lung diffusing capacity with exercise before and after pneumonectomy in dogs. J. Appl. Physiol. 70: 135-142, 1991. [Abstract/Free Full Text] .
4. Crapo, R. O., J. D. Crapo, and A. H. Morris. Lung tissue and capillary blood volumes by rebreathing and morphometric techniques. Respir. Physiol. 49: 175-186, 1982. [Medline] .
5. Davies, P., J. McBride, G. F. Murray, B. R. Wilcox, J. A. Shallal, and L. Reid. Structural changes in the canine lung and pulmonary arteries after pneumonectomy. J. Appl. Physiol. 53: 859-864, 1982. [Abstract/Free Full Text] .
6. Ford, G. T., W. Galaugher, L. Forkert, J. A. Fleetham, W. M. Thurlbeck, and N. R. Anthonisen. Static lung function in puppies after pneumonectomy. J. Appl. Physiol. 50: 1146-1150, 1981. [Abstract/Free Full Text] .
7. Georgopoulos, D., S. N. Mink, L. Oppenheimer, and N. R. Anthonisen. How is maximal expiratory flow reduced in canine postpneumonectomy lung growth? J. Appl. Physiol. 71: 834-840, 1991. [Abstract/Free Full Text] .
8. Greville, H. W., M. E. Arnup, S. N. Mink, L. Oppenheimer, and N. R. Anthonisen. Mechanism of reduced maximum expiratory flow in dogs with compensatory lung growth. J. Appl. Physiol. 60: 441-448, 1986. [Abstract/Free Full Text] .
9. Hsia, C. C. W., F. Fryder-Doffey, R. C. Reynolds, R. L. Johnson, Jr., and E. R. Weibel. Structural changes underlying compensatory increase of diffusing capacity after left pneumonectomy in adult dogs. J. Clin. Invest. 92: 758-764, 1993. .
10. Hsia, C. C. W., L. F. Herazo, F. Fryder-Doffey, and E. R. Weibel. Compensatory lung growth occurs in adult dogs after right pneumonectomy. J. Clin. Invest. 94: 405-412, 1994. .
11. Hsia, C. C. W., L. F. Herazo, M. Ramanathan, H. Claassen, F. Fryder-Doffey, H. Hoppeler, and R. L. Johnson, Jr. Cardiopulmonary adaptations to pneumonectomy in dogs. III. Ventilatory power requirements and muscle structure. J. Appl. Physiol. 76: 2191-2198, 1994. [Abstract/Free Full Text] .
12. Hsia, C. C. W., L. F. Herazo, M. Ramanathan, and R. L. Johnson, Jr. Cardiopulmonary adaptations to pneumonectomy in dogs. IV. Membrane diffusing capacity and capillary blood volume. J. Appl. Physiol. 77: 998-1005, 1994. [Abstract/Free Full Text] .
13. Hyde, R. W., J. C. Wandtke, P. J. Fahey, M. J. Utell, D. B. Plewes, and M. Goske. Lung weight in vivo measured with computed tomography and rebreathing of soluble gases. J. Appl. Physiol. 67: 166-173, 1989. [Abstract/Free Full Text] .
14. Johnson, R. L., Jr., S. S. Cassidy, R. Grover, M. Ramanathan, A. Estrera, R. C. Reynolds, R. Epstein, and J. Schutte. Effect of pneumonectomy on the remaining lung in dogs. J. Appl. Physiol. 70: 849-858, 1991. [Abstract/Free Full Text] .
15. Johnson, R. L., Jr., S. S. Cassidy, R. F. Grover, J. E. Schutte, and R. H. Epstein. Functional capacities of lungs and thorax in beagles after prolonged residence at 3,100 m. J. Appl. Physiol. 59: 1773-1782, 1985. [Abstract/Free Full Text] .
16. Kirchner, K. K., and J. T. McBride. Changes in airway length after unilateral pneumonectomy in weanling ferrets. J. Appl. Physiol. 68: 187-192, 1990. [Abstract/Free Full Text] .
17. McBride, J. T. Postpneumonectomy airway growth in the ferret. J. Appl. Physiol. 58: 1010-1014, 1985. [Abstract/Free Full Text] .
18. Mink, S. N., S. G. Holtby, D. J. Berezanski, L. Oppenheimer, and N. R. Anthonisen. Heterogeneity of maximal lobar emptying rates in dogs with compensatory lung growth. J. Appl. Physiol. 67: 1164-1170, 1989. [Abstract/Free Full Text] .
19. Olson, L. E., and E. A. Hoffman. Lung volumes and distribution of regional air content determined by cine X-ray CT of pneumonectomized rabbits. J. Appl. Physiol. 76: 1774-1785, 1994. [Abstract/Free Full Text] .
20. Peterson, B. T., M. F. Petrini, R. W. Hyde, and B. F. Schreiner. Pulmonary tissue volume in dogs during pulmonary edema. J. Appl. Physiol. 44: 782-795, 1978. [Abstract/Free Full Text] .
21. Takeda, S., M. Ramanathan, E. Y. Wu, A. S. Estrera, and C. C. W. Hsia. Temporal course of gas exchange and mechanical compensation after right pneumonectomy in immature dogs. J. Appl. Physiol. 80: 1304-1312, 1996. [Abstract/Free Full Text] .
22. Thurlbeck, W. M., W. Galaugher, and J. Mathers. Adaptive response to pneumonectomy in puppies. Thorax 36: 424-427, 1981. [Abstract] .
23. Wandtke, J. C., R. W. Hyde, P. J. Fahey, M. J. Utell, D. B. Plewes, M. J. Goske, and H. W. Fischer. Measurement of lung gas volume and regional density by computed tomography in dogs. Invest. Radiol. 21: 108-117, 1986. [Medline] .
24. Wilcox, B. R., G. F. Murray, M. Friedman, and R. L. Pimmel. The effects of early pneumonectomy on the remaining pulmonary parenchyma. Surgery 86: 294-300, 1979. [Medline] .
0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society


This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
P. Ravikumar, C. Yilmaz, D. M. Dane, R. L. Johnson Jr., A. S. Estrera, C. C. W. Hsia, and (With the Technical Assistance of Richard T. Hogg
Developmental signals do not further accentuate nonuniform postpneumonectomy compensatory lung growth
J Appl Physiol, March 1, 2007; 102(3): 1170 - 1177.
[Abstract] [Full Text] [PDF]

Home page
 ERRHome page
C. C. W. Hsia
Quantitative morphology of compensatory lung growth
Eur. Respir. Rev., December 1, 2006; 15(101): 148 - 156.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
S.-i. Takeda, Y. Funakoshi, Y. Kadota, M. Koma, H. Maeda, S. Kawamura, and Y. Matsubara
Fall in diffusing capacity associated with induction therapy for lung cancer: a predictor of postoperative complication?
Ann. Thorac. Surg., July 1, 2006; 82(1): 232 - 236.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. Mae, T. P. O'Connor, and R. G. Crystal
Gene Transfer of the Vascular Endothelial Growth Factor Receptor flt-1 Suppresses Pulmonary Metastasis Associated with Lung Growth
Am. J. Respir. Cell Mol. Biol., December 1, 2005; 33(6): 629 - 635.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
P. Ravikumar, C. Yilmaz, D. M. Dane, R. L. Johnson Jr., A. S. Estrera, and C. C. W. Hsia
Regional lung growth following pneumonectomy assessed by computed tomography
J Appl Physiol, October 1, 2004; 97(4): 1567 - 1574.
[Abstract] [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
 J. Appl. Physiol.Home page
C. C. W. Hsia, X. Yan, D. M. Dane, and R. L. Johnson Jr.
Density-dependent reduction of nitric oxide diffusing capacity after pneumonectomy
J Appl Physiol, May 1, 2003; 94(5): 1926 - 1932.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
D. M. Dane, R. L. Johnson Jr., and C. C. W. Hsia
Dysanaptic growth of conducting airways after pneumonectomy assessed by CT scan
J Appl Physiol, October 1, 2002; 93(4): 1235 - 1242.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
E. Y. Wu, C. C. W. Hsia, A. S. Estrera, R. H. Epstein, M. Ramanathan, and R. L. Johnson Jr
Preventing mediastinal shift after pneumonectomy does not abolish physiological compensation
J Appl Physiol, July 1, 2000; 89(1): 182 - 191.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. C. W. Hsia, X. S. Zhou, D. J. Bellotto, and H. K. Hagler
Regenerative growth of respiratory bronchioles in dogs
Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L136 - L142.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
S.-i. Takeda, A. S. Estrera, and C. C. W. Hsia
In vivo estimation of septal lung tissue volume and correlation with diffusing capacity in lung volume reduction surgery
J. Thorac. Cardiovasc. Surg., January 1, 2000; 119(1): 191 - 192.
[Full Text]

Home page
 J. Appl. Physiol.Home page
S.-I. Takeda, M. Ramanathan, A. S. Estrera, and C. C. W. Hsia
Postpneumonectomy alveolar growth does not normalize hemodynamic and mechanical function
J Appl Physiol, August 1, 1999; 87(2): 491 - 497.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
G. Manier, M. Duclos, L. Arsac, J. Moinard, and F. Laurent
Distribution of lung density after strenuous, prolonged exercise
J Appl Physiol, July 1, 1999; 87(1): 83 - 89.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
S.-I. Takeda, C. C. W. Hsia, E. Wagner, M. Ramanathan, A. S. Estrera, and E. R. Weibel
Compensatory alveolar growth normalizes gas-exchange function in immature dogs after pneumonectomy
J Appl Physiol, April 1, 1999; 86(4): 1301 - 1310.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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 Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Takeda, S.
Right arrow Articles by Hsia, C. C. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takeda, S.
Right arrow Articles by Hsia, C. C. W.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online