Chronic lung injury in preterm lambs: Abnormalities of the pulmonary circulation and lung fluid balance

Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature b irth. Pulmonary hypertension and edema are common features of this conditio n, which is often attributed to long-term, repetitive overinflation of inco mpletely developed lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and lung fluid balance of differe nt ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs tha t were delivered prematurely (124 +/- 3 d gestation, term = 147 d) by cesar ean section and mechanically ventilated for 3 to 4 wk. Ten lambs were venti lated at 20 breaths/min, yielding a tidal Volume of 15 +/- 5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal volume of 6 +/- 2 mL/kg. All lambs received surfactant at birth and had subsequent surgery for closure of the ductus arteriosus and catheter placement to allow serial measurements of pulmonary vascular resistance and lung lymph flow. Chronic lung injury, documented by serial chest radiographs and postmortem patholo gic examination, developed in all lambs irrespective of the pattern of assi sted ventilation. Pulmonary vascular resistance, which normally decreases d uring the month after birth at term, did not change significantly from the first to the last week of study. Lung lymph flow, an index of net transvasc ular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph prote in concentration decreased with time, indicative of increased fluid filtrat ion pressure, without evidence of a change in lung vascular protein permeab ility. Postmortem studies showed interstitial lung edema, increased pulmona ry arteriolar smooth muscle and elastin, decreased numbers of small pulmona ry arteries and veins, and decreased capillary surface density in distal lu ng of chronically ventilated lambs compared with control lambs that were ki lled either 1 d (same postconceptional age) or 3 wk (same postnatal age) af ter birth at term. Thus, chronic lung injury from prolonged mechanical vent ilation after premature birth inhibits the normal postnatal decrease in pul monary vascular resistance and leads to lung edema from increased fluid fil tration pressure. These abnormalities of the pulmonary circulation may cont ribute to the abnormal respiratory gas exchange that often exists in infant s with bronchopulmonary dysplasia.