Abstract
Chronic lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature birth. Pulmonary hypertension and edema are common features of this condition, which is often attributed to long-term, repetitive overinflation of incompletely developed lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and lung fluid balance of different ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs that were delivered prematurely (124 ± 3 d gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to 4 wk. Ten lambs were ventilated 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 pathologic examination, developed in all lambs irrespective of the pattern of assisted ventilation. Pulmonary vascular resistance, which normally decreases during 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 transvascular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph protein concentration decreased with time, indicative of increased fluid filtration pressure, without evidence of a change in lung vascular protein permeability. Postmortem studies showed interstitial lung edema, increased pulmonary arteriolar smooth muscle and elastin, decreased numbers of small pulmonary arteries and veins, and decreased capillary surface density in distal lung of chronically ventilated lambs compared with control lambs that were killed either 1 d (same postconceptional age) or 3 wk (same postnatal age) after birth at term. Thus, chronic lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance and leads to lung edema from increased fluid filtration pressure. These abnormalities of the pulmonary circulation may contribute to the abnormal respiratory gas exchange that often exists in infants with bronchopulmonary dysplasia.
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Abbreviations
- BPD:
-
bronchopulmonary dysplasia
- CLD:
-
chronic lung disease of early infancy
- PVR:
-
pulmonary vascular resistance
- Fio2:
-
fraction of O2 in the inspired gas
- Pao2:
-
Po2 in arterial blood
- Paco2:
-
Pco2 in arterial blood
- L/P:
-
lymph protein concentration to plasma protein concentration
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Acknowledgements
This work would have been impossible to complete without the help of numerous people who are not listed as authors. We are especially grateful to the many University of Utah medical students, part-time technicians, and respiratory therapists who assisted in the daily management of the lambs. We also thank Dr. Edmund Egan (Ony, Inc) for generously providing bovine surfactant (Infasurf), Gail Ellison for performing weekly lung function studies, Nancy Chandler and James Marcelo for microscopy assistance, Dr. Howard Corneli for statistical advice, and Sharon Marron for typing the manuscript.
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Supported in part by grants from the March of Dimes (6-FY97–0138) and the American Heart Association (96014370).
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Bland, R., Albertine, K., Carlton, D. et al. Chronic Lung Injury in Preterm Lambs: Abnormalities of the Pulmonary Circulation and Lung Fluid Balance. Pediatr Res 48, 64–74 (2000). https://doi.org/10.1203/00006450-200007000-00013
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DOI: https://doi.org/10.1203/00006450-200007000-00013
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