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The Perinatal Asphyxiated Lamb Model: A Model for Newborn Resuscitation
Published on: August 15, 2018
Chronic lung injury in preterm lambs: abnormalities of the pulmonary circulation and lung fluid balance
R D Bland1, K H Albertine, D P Carlton
1Department of Pediatrics, University of Utah, Salt Lake City 84132, USA.
Insights
Mechanical ventilation strategies impact lung injury in premature lambs. Lower ventilation rates with larger volumes worsened lung edema, unlike higher rates with smaller volumes, suggesting a ventilation strategy may mitigate bronchopulmonary dysplasia complications.
Area of Science:
- Neonatology
- Pulmonary Medicine
- Pediatric Critical Care
Background:
- Bronchopulmonary dysplasia (BPD) is a common complication in premature infants requiring mechanical ventilation.
- Pulmonary hypertension and edema are characteristic features of BPD, often linked to lung overinflation.
- Understanding the effects of different ventilation strategies on pulmonary circulation and fluid balance is crucial for managing BPD.
Purpose of the Study:
- To investigate the impact of varying tidal volumes (large vs. small) during mechanical ventilation on pulmonary circulation and lung fluid balance in an animal model of BPD.
- To determine if different ventilation patterns affect the development of chronic lung injury and associated pulmonary abnormalities.
Main Methods:
- Prematurely delivered lambs (n=16) underwent mechanical ventilation for 3-4 weeks.
- Two ventilation groups were studied: 20 breaths/min (large tidal volume, 15±5 mL/kg) and 60 breaths/min (small tidal volume, 6±2 mL/kg).
- Serial measurements of pulmonary vascular resistance and lung lymph flow were conducted, with postmortem pathological examination.
Main Results:
- All lambs developed chronic lung injury regardless of ventilation strategy.
- Pulmonary vascular resistance did not decrease postnatally as expected.
- Lung lymph flow increased over time in the large tidal volume group (20 breaths/min), indicating increased fluid filtration, but not in the small tidal volume group (60 breaths/min).
- Postmortem analysis revealed interstitial edema, vascular remodeling, and reduced capillary density in ventilated lambs.
Conclusions:
- Prolonged mechanical ventilation in premature lambs inhibits normal postnatal pulmonary vascular resistance changes and causes lung edema due to increased fluid filtration pressure.
- Ventilation with smaller tidal volumes may be beneficial in mitigating pulmonary circulatory abnormalities and lung edema in BPD.
- These findings suggest that ventilation strategies can influence the severity of BPD-related pulmonary complications.
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.
