Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure

Kara N. Goss, Anthony R. Cucci, Amanda J. Fisher, Marjorie Albrecht, Andrea Frump, Roziya Tursunova, Yong Gao, Mary Beth Brown, Irina Petrache, Robert S. Tepper, Shawn K. Ahlfeld, Tim Lahm

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (P<inf>atm</inf>=362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults.

Original languageEnglish (US)
Pages (from-to)L797-L806
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume308
Issue number8
DOIs
StatePublished - Jan 1 2015

Fingerprint

Hyperoxia
Ventricular Remodeling
Lung Injury
Pulmonary Hypertension
Blood Vessels
Lung
Air
Oxygen
Right Ventricular Hypertrophy
Right Ventricular Function
Ventricular Pressure
Secondary Prevention
Pulmonary Artery
Hypoxia
Blood Pressure
Phenotype
Pressure
Genes

Keywords

  • Atrial natriuretic peptide
  • Prematurity
  • Pulmonary hypertension capillarization
  • Right ventricular adaptation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure. / Goss, Kara N.; Cucci, Anthony R.; Fisher, Amanda J.; Albrecht, Marjorie; Frump, Andrea; Tursunova, Roziya; Gao, Yong; Brown, Mary Beth; Petrache, Irina; Tepper, Robert S.; Ahlfeld, Shawn K.; Lahm, Tim.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 308, No. 8, 01.01.2015, p. L797-L806.

Research output: Contribution to journalArticle

Goss, Kara N. ; Cucci, Anthony R. ; Fisher, Amanda J. ; Albrecht, Marjorie ; Frump, Andrea ; Tursunova, Roziya ; Gao, Yong ; Brown, Mary Beth ; Petrache, Irina ; Tepper, Robert S. ; Ahlfeld, Shawn K. ; Lahm, Tim. / Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2015 ; Vol. 308, No. 8. pp. L797-L806.
@article{5cc63dbb44be46cc96102be496828c70,
title = "Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure",
abstract = "The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90{\%} oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm=362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults.",
keywords = "Atrial natriuretic peptide, Prematurity, Pulmonary hypertension capillarization, Right ventricular adaptation",
author = "Goss, {Kara N.} and Cucci, {Anthony R.} and Fisher, {Amanda J.} and Marjorie Albrecht and Andrea Frump and Roziya Tursunova and Yong Gao and Brown, {Mary Beth} and Irina Petrache and Tepper, {Robert S.} and Ahlfeld, {Shawn K.} and Tim Lahm",
year = "2015",
month = "1",
day = "1",
doi = "10.1152/ajplung.00276.2014",
language = "English (US)",
volume = "308",
pages = "L797--L806",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "8",

}

TY - JOUR

T1 - Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure

AU - Goss, Kara N.

AU - Cucci, Anthony R.

AU - Fisher, Amanda J.

AU - Albrecht, Marjorie

AU - Frump, Andrea

AU - Tursunova, Roziya

AU - Gao, Yong

AU - Brown, Mary Beth

AU - Petrache, Irina

AU - Tepper, Robert S.

AU - Ahlfeld, Shawn K.

AU - Lahm, Tim

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm=362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults.

AB - The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm=362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults.

KW - Atrial natriuretic peptide

KW - Prematurity

KW - Pulmonary hypertension capillarization

KW - Right ventricular adaptation

UR - http://www.scopus.com/inward/record.url?scp=84927782486&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927782486&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00276.2014

DO - 10.1152/ajplung.00276.2014

M3 - Article

C2 - 25659904

AN - SCOPUS:84927782486

VL - 308

SP - L797-L806

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 8

ER -