Abstract
Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model, using former-preterm lambs, to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former-preterm lambs. Results are compared with term control lambs that were not ventilated, and between males (M) and females (F). Alveolar simplification was quantified morphometrically and stereologically at 2 mo (4 M, 4 F) or 5 mo (4 M, 6 F) corrected postnatal age (cPNA) compared with unventilated, age-matched term control lambs (4 M, 4 F per control group). These postnatal ages in sheep are equivalent to human postnatal ages of 1-2 yr and ~6 yr, respectively. Multivariable linear regression results showed that former-preterm lambs at 2 or 5 mo cPNA had significantly thicker distal airspace walls (P < 0.001 and P < 0.009, respectively), lower volume density of secondary septa (P < 0.007 and P < 0.001, respectively), and lower radial alveolar count (P < 0.003 and P < 0.020, respectively) compared with term control lambs. Sex-specific differences were not detected. We conclude that moderate preterm birth and MV for ~6 days impedes completion of alveolarization in former-preterm lambs. This new model provides the opportunity to identify underlying pathogenic mechanisms that may reveal treatment approaches.
| Original language | English (US) |
|---|---|
| Pages (from-to) | L816-L833 |
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 315 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 1 2018 |
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Keywords
- Alveolar capillary growth
- Alveolar formation
- Bronchopulmonary dysplasia
- Lung development
- Neonatal chronic lung disease
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology
Cite this
Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age. / Dahl, Mar Janna; Bowen, Sydney; Aoki, Toshio; Rebentisch, Andrew; Dawson, Elaine; Pettet, Luke; Emerson, Haleigh; Yu, Baifeng; Wang, Zhengming; Yang, Haixia; Zhang, Chong; Presson, Angela P.; Joss-Moore, Lisa; Null, Donald; Yoder, Bradley A.; Albertine, Kurt H.
In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 315, No. 5, 01.11.2018, p. L816-L833.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age
AU - Dahl, Mar Janna
AU - Bowen, Sydney
AU - Aoki, Toshio
AU - Rebentisch, Andrew
AU - Dawson, Elaine
AU - Pettet, Luke
AU - Emerson, Haleigh
AU - Yu, Baifeng
AU - Wang, Zhengming
AU - Yang, Haixia
AU - Zhang, Chong
AU - Presson, Angela P.
AU - Joss-Moore, Lisa
AU - Null, Donald
AU - Yoder, Bradley A.
AU - Albertine, Kurt H.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model, using former-preterm lambs, to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former-preterm lambs. Results are compared with term control lambs that were not ventilated, and between males (M) and females (F). Alveolar simplification was quantified morphometrically and stereologically at 2 mo (4 M, 4 F) or 5 mo (4 M, 6 F) corrected postnatal age (cPNA) compared with unventilated, age-matched term control lambs (4 M, 4 F per control group). These postnatal ages in sheep are equivalent to human postnatal ages of 1-2 yr and ~6 yr, respectively. Multivariable linear regression results showed that former-preterm lambs at 2 or 5 mo cPNA had significantly thicker distal airspace walls (P < 0.001 and P < 0.009, respectively), lower volume density of secondary septa (P < 0.007 and P < 0.001, respectively), and lower radial alveolar count (P < 0.003 and P < 0.020, respectively) compared with term control lambs. Sex-specific differences were not detected. We conclude that moderate preterm birth and MV for ~6 days impedes completion of alveolarization in former-preterm lambs. This new model provides the opportunity to identify underlying pathogenic mechanisms that may reveal treatment approaches.
AB - Preterm birth and mechanical ventilation (MV) frequently lead to bronchopulmonary dysplasia, the histopathological hallmark of which is alveolar simplification. How developmental immaturity and ongoing injury, repair, and remodeling impact completion of alveolar formation later in life is not known, in part because of lack of suitable animal models. We report a new model, using former-preterm lambs, to test the hypothesis that they will have persistent alveolar simplification later in life. Moderately preterm lambs (~85% gestation) were supported by MV for ~6 days before being transitioned from all respiratory support to become former-preterm lambs. Results are compared with term control lambs that were not ventilated, and between males (M) and females (F). Alveolar simplification was quantified morphometrically and stereologically at 2 mo (4 M, 4 F) or 5 mo (4 M, 6 F) corrected postnatal age (cPNA) compared with unventilated, age-matched term control lambs (4 M, 4 F per control group). These postnatal ages in sheep are equivalent to human postnatal ages of 1-2 yr and ~6 yr, respectively. Multivariable linear regression results showed that former-preterm lambs at 2 or 5 mo cPNA had significantly thicker distal airspace walls (P < 0.001 and P < 0.009, respectively), lower volume density of secondary septa (P < 0.007 and P < 0.001, respectively), and lower radial alveolar count (P < 0.003 and P < 0.020, respectively) compared with term control lambs. Sex-specific differences were not detected. We conclude that moderate preterm birth and MV for ~6 days impedes completion of alveolarization in former-preterm lambs. This new model provides the opportunity to identify underlying pathogenic mechanisms that may reveal treatment approaches.
KW - Alveolar capillary growth
KW - Alveolar formation
KW - Bronchopulmonary dysplasia
KW - Lung development
KW - Neonatal chronic lung disease
UR - http://www.scopus.com/inward/record.url?scp=85059751216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059751216&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00249.2018
DO - 10.1152/ajplung.00249.2018
M3 - Article
C2 - 30211655
AN - SCOPUS:85059751216
VL - 315
SP - L816-L833
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 1040-0605
IS - 5
ER -