Chronic lung injury from prolonged mechanical ventilation after premature birth is characterized in part by pulmonary edema and sustained pulmonary vascular resistance (PVR) (Bland et al; FASEB J 9:A275, 1995). These observations suggest that chronic lung injury after premature birth may be associated with abnormal structural development of the pulmonary circulation. We tested this hypothesis by determining smooth muscle extension and elastin accumulation along pulmonary arteries (PAs) and veins (PVs) in 3 groups of lambs. 5 preterm lambs each were mechanically ventilated at 60 breaths/min(tidal volume 5 ± 2 ml/kg) or 20 breaths/min (tidal volume 15 ± 5 ml/kg) for 3-4 wks postnatally. Inspired O2 was adjusted to keep PaO2 ≈60-90 mmHg. 5 term lambs <24 h old served as gestation-matched controls. Lung lobes were fixed by clamping them at the prevailing inflation pressure. Paraffin-embedded tissue sections were analyzed for vascular smooth muscle extension (trichrome stain) and elastin accumulation (Hart's elastic fiber stain) along PAs and PVs by quantitative histology (mean ± SD; *:p < 0.05 vs control). Muscularization of PAs and elastin accumulation in PAs and PVs may contribute to the histologic and extravascular lung water content evidence of pulmonary edema, and the sustained PVR by increasing the filtration pressure and resistance along the pulmonary microcirculation. (Supported by March of Dimes #6 FY95 0981)Table

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