Systemic heparin administration impairs lung development in neonatal mice.

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.