Basic Science Article | Published:

Fetal growth restriction is associated with an altered cardiopulmonary and cerebral hemodynamic response to surfactant therapy in preterm lambs

Abstract

Background

Efficacy of surfactant therapy in fetal growth restricted (FGR) preterm neonates is unknown.

Methods

Twin-bearing ewes underwent surgery at 105 days gestation to induce FGR in one twin by single umbilical artery ligation. At 123–127 days, catheters and flow probes were implanted in pulmonary and carotid arteries to measure flow and pressure. Lambs were delivered, intubated and mechanically ventilated. At 10 min, surfactant (100 mg kg−1) was administered. Ventilation, oxygenation, and hemodynamic responses were recorded for 1 h before euthanasia at 120 min. Lung tissue and bronchoalveolar lavage fluid was collected for analysis of surfactant protein mRNA and phosphatidylcholines (PCs).

Results

FGR preterm lambs were 26% lighter than appropriate for gestational age (AGA) lambs and had baseline differences in lung mechanics and pulmonary blood flows. Surfactant therapy reduced ventilator and oxygen requirements and improved lung mechanics in both groups, although a more rapid improvement in compliance and tidal volume was observed in AGA lambs. Surfactant administration was associated with decreased mean pulmonary and carotid blood flow in FGR but not AGA lambs. No major differences in surfactant protein mRNA or PC levels were noted.

Conclusions

Surfactant therapy was associated with an altered pulmonary and cerebral hemodynamic response in preterm FGR lambs.

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Acknowledgements

We thank Ilias Nitsos, Kelly Crossley, and Dalibor Stanojkovic for their help with animal experiments. This research was supported by National Health and Medical Research Council (NH&MRC) Project Grant (APP1083520), the Arthur & Mary Osborn Charitable Trust, and the Hugh D T Williamson Foundation, which are managed by ANZ Trustees; a Royal Australasian College of Physicians Foundation Fellowship (to A.M.); NH&MRC Research Fellowships (to G.R.P.: APP1105526; to S.L.M.: APP1136216; and to S.B.H.: APP545921); an Australian Research Council Future Fellowship (to S.L.M.: FT1301006); a Rebecca L. Cooper Medical Research Foundation Fellowship (to G.R.P.); and the Victorian Government’s Operational Infrastructure Support Program.

Author information

All authors were involved in the conduct of the experiments, acquisition of data, analysis, and preparation of the manuscript. A.M. designed the experimental plan and wrote the first draft of the manuscript. G.R.P. is the senior author, critically analyzed the data, and provided statistical input to the manuscript. F.S. and V.Z. conducted the surfactant analysis.

Competing interests

The authors declare no competing interests.

Correspondence to Atul Malhotra.

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