| Description |
Preterm infants who are mechanically ventilated are at risk of developing bronchopulmonary dysplasia (BPD). Low level of insulin-like growth factor 1 (IGF-1) protein in plasma of preterm infant is associated with development of BPD. Low level of IGF-1 protein is important because IGF-1 is a morphogen that is necessary for organ development. Normally, the fetal source of IGF-1 during pregnancy is the mother. But following preterm birth, that source is not available, thus reducing the level of this necessary morphogen in the preterm infant. We used our preterm lamb model of BPD to determine if recombinant human (rh) IGF-1 complexed with its principal binding protein 3 (rhIGFBP-3) to replenish IGF-1 protein to a normal level will increase structural indices of alveolar capillary growth in the lung. We used an optimized dose of the IGF-1 complex. Preterm lambs (delivered at about 128 days gestation; equivalent to about a 28- week preterm infant) were divided into two groups, both of which were mechanically ventilated for 7 days. The first group received continuous infusion of saline (control) while the second group was given continuous infusion of recombinant human IGF-1 (1.5mg/Kg/d). Lung tissue was analyzed for structural formation of alveolar capillaries, using an anti-platelet endothelial cell adherence molecule 1 (anti-PECAM-1) antibody to reveal capillary endothelial cells. Stereology (quantitative histology) was used to quantify capillary surface density as well as epithelial cell surface density. We hypothesized that treatment with rhIGF-1 complex will increase capillary surface density in mechanically ventilated preterm lambs. If this result is the outcome, our results will contribute to rationale for treating preterm infants at risk of developing BPD with the rhIGF-1 complex. The significance of such a contribution is that no effective treatment exists for BPD, which was first reported in 1967. Thus, our results could have a large impact on the field of neonatology. |
