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Updated: May 9, 2025
Intravenous Injections in Neonatal Mice
Published on: November 11, 2014
Systemic heparin administration impairs lung development in neonatal mice
Thomas I Hirsch1,2, Savas T Tsikis1,2, Scott C Fligor1,2
1Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Insights
Heparin administration during the saccular stage of lung development in neonatal mice negatively impacts lung growth, causing emphysema. Late heparin exposure did not affect lung development, suggesting a critical developmental window for heparin
Area of Science:
- Neonatal physiology
- Pulmonary medicine
- Pharmacology
Background:
- Preterm infants face bronchopulmonary dysplasia (BPD) risk due to saccular stage lung development.
- Oxygen toxicity and volutrauma are known BPD contributors, yet chronic lung disease persists.
- Heparin, commonly used in neonates, interferes with angiogenesis, crucial for lung development.
Purpose of the Study:
- To investigate the impact of heparin on neonatal lung development during the saccular phase.
- To determine if early-life heparin exposure affects lung structure and function in mice.
Main Methods:
- Newborn C57BL/6J mice received unfractionated heparin (UFH), low molecular weight heparin (LMWH), or saline (control) for the first week.
- Lung phenotype was assessed at one month of age.
- Heparin administration after the saccular phase was also evaluated.
Main Results:
- Both UFH and LMWH administered during the first week resulted in an emphysematous lung phenotype at one month.
- Late heparin administration, post-saccular phase, did not impact lung function or growth.
- Heparin interferes with critical postnatal lung development.
Conclusions:
- Heparin negatively affects lung development when administered during the critical saccular phase in neonatal mice.
- These findings highlight potential risks of early-life heparin exposure in preterm infants.
- Clinical studies are warranted to investigate heparin's impact on infant lung development.
Abstract:
Preterm infants born in the saccular stage of lung development are at risk for developing bronchopulmonary dysplasia (BPD). Oxygen toxicity and volutrauma are identified as major contributors of BPD. Despite mitigation of these risks preterm infants continue to be affected by chronic lung disease. Heparin is commonly administered to preterm infants and is known to interfere with angiogenesis, a critical element of lung development. We previously demonstrated, in a murine model, that compensatory lung growth after left pneumonectomy is inhibited by heparin administration. Based on these results, we hypothesized that heparin would interfere with lung development in neonatal mice, which are born during the saccular phase of lung development. Newborn C57BL/6J mice received either therapeutic unfractionated heparin (UFH), low molecular weight heparin (LMWH) or normal saline (control) for the first week of life. At one month, both UFH and LMWH produced an emphysematous lung phenotype. Late administration of heparin, after the saccular phase did not impact lung function or growth. This data establishes the negative effects of UFH and LMWH during the critical period of postnatal lung development. Based on this work, clinical studies on the impact of heparin on lung development of newborn and preterm infants are warranted.
