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Vascular Endothelial Growth Factor Accelerates Compensatory Lung Growth by Increasing Alveolar Units
*Duy Dao, *Prathima Nandivada, *Amy Pan, *Lorenzo Anez-Bustillos, *Meredith Baker, *Gillian Fell, *Thomas Martin, Mark Puder
Boston Children's Hospital, Boston, MA
Objectives: We have previously shown that exogenous administration of vascular endothelial growth factor (VEGF) accelerates compensatory lung growth in mice after unilateral pneumonectomy. In this study, we seek to determine how VEGF alters pulmonary mechanical properties and architecture of the regenerating lung.
Design: Eight-to-ten week-old C57Bl/6 male mice underwent left pneumonectomy, followed by daily intraperitoneal injection of saline or VEGF at a dose of 0.5 mg/kg. Pulmonary mechanical properties were measured on post-operative day (POD) 4 or 10, immediately before euthanasia. Lung volume was determined by a volume displacement method and morphometric studies were performed utilizing a point-counting technique. All volume and surface area measurements were normalized against body weight.
Setting: Laboratory
Patients (or Other Participants): Mice
Interventions: VEGF
Main Outcome Measure(s): Lung volume, pulmonary mechanical properties, and morphometric analyses
Results: Lung volume to body weight ratio on POD 4 is significantly higher in the VEGF-treated mice compared to the saline group (0.059±0.005 vs. 0.052±0.008 mL/g, p=0.02, n=13). Area under the pressure-volume loop, which corresponds to the number of alveolar units, was significantly increased by VEGF treatment on POD 4 (0.124±0.028 vs. 0.097±0.033 cmH2O.mL/g, p=0.04, n=12). On morphometric analyses, VEGF significantly increased parenchymal volume (0.047±0.003 vs. 0.038±0.005 mL/g, p<0.01, n=5), alveolar volume (0.030±0.001 vs. 0.023±0.003 mL/g, p<0.01, n=5), and septal surface area (19.0±1.4 vs. 15.4±1.8 cm2/g, p<0.01, n=5) on POD 4. Additionally, the alveolar to parenchymal volume ratio was similar in both groups, indicating preserved pulmonary architecture with VEGF treatment.
Conclusions: VEGF accelerates compensatory lung growth by increasing alveolar units without altering pulmonary mechanics or architecture. These findings highlight the potential of VEGF as a novel therapy in the treatment of severe pulmonary hypoplasia.
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