Functional morphometry to estimate the alveolar surface area by using a premature baboon model

Author(s):  
Theodore Dassios ◽  
Mario Rüdiger ◽  
Donald McCurnin ◽  
Steven R. Seidner ◽  
Emma E. Williams ◽  
...  

The main respiratory pathophysiological process following premature birth is the delayed or arrested alveolar development which translates to a smaller alveolar surface area (S­A). Histological morphometry is the gold standard method to measure the SA but requires invasive tissue sampling or the removal of the whole organ for analysis. Alternatively, the SA could be measured in living subjects by "functional morphometry" using Fick's first law of diffusion and non-invasive measurements of the ventilation perfusion ratio (VA/Q). We herein aim to describe a novel functional morphometric method to measure SA using a premature baboon model. We used both functional morphometry and post-mortem histological morphometry to measure SA in 11 premature baboons born at 135 days who received intensive care treatment for 14 days. For the calculation of the SA by functional morphology we measured the septal wall thickness using microscopy, the alveolar arterial oxygen gradient using concurrent measurements of arterial pressure of O2 and CO2 and pulmonary perfusion using echocardiography and integrated Doppler signals. The median (IQR) SA using functional morphometry was 3,100 (2,080-3,640) cm2 and using histological morphometry was 1,034 (634-1,210) cm2 (left lung only). The SA measured by functional morphometry was not related to the SA measured by histological morphometry. Following linear regression analysis, the VA/Q significantly predicted the histologically measured SA (R2=0.659,p=0.002). In conclusion, functional measurements of ventilation to perfusion ratio could be used to estimate the alveolar surface area in prematurely born baboons and the ventilation perfusion ratio was the main determinant of the alveolar surface area.

Author(s):  
Theodore Dassios ◽  
Mario Rudiger ◽  
Donald Mccurnin ◽  
Emma Williams ◽  
Anne Greenough ◽  
...  

2002 ◽  
Vol 34 (4) ◽  
pp. 278-286 ◽  
Author(s):  
M.G. Davey ◽  
H.L. Hedrick ◽  
J.M. Mendoza ◽  
M. Kanai ◽  
N.S. Adzick ◽  
...  

2008 ◽  
Vol 105 (1) ◽  
pp. 249-259 ◽  
Author(s):  
Kewu Huang ◽  
Richard Rabold ◽  
Eric Abston ◽  
Brian Schofield ◽  
Vikas Misra ◽  
...  

Leptin modulates energy metabolism and lung development. We hypothesize that the effects of leptin on postnatal lung development are volume dependent from 2 to 10 wk of age and are independent of hypometabolism associated with leptin deficiency. To test the hypotheses, effects of leptin deficiency on lung maturation were characterized in age groups of C57BL/6J mice with varying Lep ob genotypes. Quasi-static pressure-volume curves and respiratory impedance measurements were performed to profile differences in respiratory system mechanics. Morphometric analysis was conducted to estimate alveolar size and number. Oxygen consumption was measured to assess metabolic rate. Lung volume at 40-cmH2O airway pressure (V40) increased with age in each genotypic group, and V40 was significantly ( P < 0.05) lower in leptin-deficient ( ob/ ob) mice beginning at 2 wk. Differences were amplified through 7 wk of age relative to wild-type (+/+) mice. Morphometric analysis showed that alveolar surface area was lower in ob/ ob compared with +/+ and heterozygote ( ob/+) mice beginning at 2 wk. Unlike the other genotypic groups, alveolar size did not increase with age in ob/ ob mice. In another experiment, ob/ ob at 4 wk received leptin replacement (5 μg·g−1·day−1) for 8 days, and expression levels of the Col1a1, Col3a1, Col6a3, Mmp2, Tieg1, and Stat1 genes were significantly increased concomitantly with elevated V40. Leptin-induced increases in V40 corresponded with enlarged alveolar size and surface area. Gene expression suggested a remodeling event of lung parenchyma after exogenous leptin replacement. These data support the hypothesis that leptin is critical to postnatal lung remodeling, particularly related to increased V40 and enlarged alveolar surface area.


2012 ◽  
Vol 138 (5) ◽  
pp. 803-813 ◽  
Author(s):  
Tilman Graulich ◽  
Suman Kumar Das ◽  
Gabriela Krasteva ◽  
Clemens Ruppert ◽  
Lars Wessels ◽  
...  

2006 ◽  
Vol 290 (5) ◽  
pp. L866-L870 ◽  
Author(s):  
Donald Massaro ◽  
Gloria DeCarlo Massaro

Female rats and mice have smaller and, per body mass (BM), more alveoli and alveolar surface area (Sa) than males of their respective species. This sexual dimorphism becomes apparent about the time of sexual maturity. It is prevented in rats (not tested in mice) by ovariectomy at age 3 wk. In female mice, estrogen receptor (ER)-α and ER-β are required for formation of alveoli of appropriate size and number. We now report the average volume of an alveolus (v̄a) and the number of alveoli per body mass (Na/BM) were not statistically different between ER-α−/− and wild type (wt) males. However, the combination of a larger value for v̄a and a smaller value for Na/BM, though neither parameter achieved a statistically significant intergroup difference, resulted in a statistically significant lower Sa/BM in ER-α−/− males compared with wt males. In ER-β−/− males, v̄a was bigger and Na/BM and Sa/BM were lower compared with wt males. Wt males had larger alveoli and lower Na/BM and Sa/BM than wt females. The wt sexual dimorphism of v̄a, Na/BM, and Sa/BM was absent in ER-α−/− mice. Alveolar size did not differ between ER-β−/− females and males but Na/BM and Sa/BM were greater in ER-β−/− females than in ER-β−/− males. The results in male mice, with prior findings in female mice, 1) demonstrate estrogen receptors have a smaller effect on alveolar dimensions in male than female mice, 2) show ER-α and ER-β are required for the sexual dimorphism of alveolar size, and 3) show ER-α is needed for the sexual dimorphism of body mass-specific alveolar number and surface area.


1989 ◽  
Vol 66 (6) ◽  
pp. 2750-2755 ◽  
Author(s):  
S. Groth ◽  
J. Mortensen ◽  
P. Lange ◽  
S. Vest ◽  
N. Rossing ◽  
...  

Pulmonary clearance (PCl) of inhaled aerosolized 99mTc-diethylenetriamine pentaacetic acid (DTPA) across the alveolocapillary membrane is diffusion limited. Therefore, if the mixing of the 99mTc-DTPA in the aqueous hypophase underlying surfactant is slow or incomplete or if there were no hypophase, an increase in the alveolar surface area occupied by 99mTc-DTPA particles would increase the absorption rate. The aim of this study was to examine whether there is an effect on PCl of changing the number of inhaled particles. The change in particle number was accomplished by a setup of four parallel jet nebulizers feeding a central delivery chamber of 400 cm3. We performed two kinds of experiments in eight healthy nonsmokers between 28 and 52 yr of age. In the first experiment, 99mTc-DTPA in saline was nebulized in one nebulizer, while saline was nebulized in the other three. In the second experiment the number of inhaled particles containing 99mTc-DTPA was increased by a factor of four by nebulizing 99mTc-DTPA in saline in all four nebulizers simultaneously. Increasing the number of inhaled 99mTc-DTPA particles caused an increase in PCl of 24.2% (P less than 0.01). We conclude that there is a slight but significant effect of changing the number of DTPA particles on PCl and that this is probably due to an uneven mixing of the 99mTc-DTPA in the aqueous hypophase underlying the surfactant lining and the alveoli.


1992 ◽  
Vol 88 (1-2) ◽  
pp. 163-170 ◽  
Author(s):  
H.J.H. Colebatch ◽  
C.K.Y. Ng

1970 ◽  
Vol 10 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Martin J. Fisher ◽  
Michael F. Wilson ◽  
Kenneth C. Weber

1978 ◽  
Vol 44 (3) ◽  
pp. 446-449 ◽  
Author(s):  
D. Bartlett ◽  
J. G. Areson

We have reinvestigated the question of whether exercise stimulates lung growth by determining body weight (BW), lung volume (LV), alveolar surface area (SA), and alveolar number (N) in Japanese waltzing mice, in their phenotypically normal littermates, and in normal albino mice. BW, LV, SA, and N were all less in waltzing mice than in their littermates; LV/BW, SA/BW, and N/BW were indistinguishable in the two groups. Age-matched albino mice had larger BW and smaller N/BW than the waltzers or their littermates. The results indicate that both waltzing mice and their nonwaltzing littermates have more highly compartmentalized lungs than albino mice of the same age. However, the data provide no support for the hypothesis that sustained exercise enhances lung growth.


1991 ◽  
Vol 70 (4) ◽  
pp. 1677-1685 ◽  
Author(s):  
B. R. Pitt ◽  
G. Lister ◽  
J. J. Perez Fontan ◽  
P. Davies

We recently reported that measurements of the maximal velocity of pulmonary endothelial angiotensin-converting enzyme (Vmax) in vivo provide information regarding microvascular surface area in the developing lamb. To obviate any subtle influences of development on Vmax aside from simple increases in surface area, we correlated Vmax with postmortem stereological assessments of alveolar surface area in the relatively mature lung of the 2-mo-old lamb (n = 14). We attempted to increase the range of surface area beyond its normal variability by injecting nine of the lambs with bleomycin, an antineoplastic agent with significant pulmonary toxicity in other species. Vmax, measured shortly after birth and then weekly, increased monotonically in all lambs. Despite their wide dispersion, Vmax and the stereological determinations correlated strongly at 2 mo of age, confirming that Vmax is a robust indicator of the surface area of the air-blood barrier. There was no significant difference in either measurement between the control lambs and those treated with bleomycin, suggesting that the newborn lamb is resistant to the effect of this agent.


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