Effect of prenatal diaphragmatic hernia on pulmonary arterial morphology

Author:

Stainsby Andrew V.12ORCID,DeKoninck Philip L. J.13ORCID,Crossley Kelly J.12ORCID,Thiel Alison1,Wallace Megan J.12,Pearson James T.45ORCID,Kashyap Aidan J.12ORCID,Croughan Michelle K.6ORCID,Allison Beth A.12ORCID,Hodges Ryan12,Thio Marta78,Flemmer Andreas W.9ORCID,McGillick Erin V.12ORCID,te Pas Arjan B.10ORCID,Hooper Stuart B.12ORCID,Kitchen Marcus J.16ORCID

Affiliation:

1. Ritchie Centre, Hudson Institute of Medical Research Melbourne Australia

2. Department of Obstetrics and Gynaecology Monash University Melbourne Australia

3. Division of Obstetrics and Fetal Medicine, Department of Obstetrics and Gynaecology Erasmus MC University Medical Center – Sophia Children's Hospital Rotterdam The Netherlands

4. National Cerebral and Cardiovascular Center Suita Japan

5. Department of Physiology Victoria Heart Institute and Monash Biomedicine Institute, Monash University Melbourne Australia

6. School of Physics and Astronomy Monash University Melbourne Australia

7. Newborn Research Centre The Royal Women's Hospital Melbourne Australia

8. The Department of Obstetrics and Gynaecology The University of Melbourne Melbourne Australia

9. Division of Neonatology Dr. von Hauner Children's Hospital and Perinatal Center LMU University Hospital Munich Germany

10. Division of Neonatology, Department of Pediatrics Leiden University Medical Center Leiden The Netherlands

Abstract

AbstractCongenital diaphragmatic hernia (CDH) is a major cause of severe lung hypoplasia and pulmonary hypertension in the newborn. While the pulmonary hypertension is thought to result from abnormal vascular development and arterial vasoreactivity, the anatomical changes in vascular development are unclear. We have examined the 3D structure of the pulmonary arterial tree in rabbits with a surgically induced diaphragmatic hernia (DH). Fetal rabbits (n = 6) had a left‐sided DH created at gestational day 23 (GD23), delivered at GD30, and briefly ventilated; sham‐operated litter mates (n = 5) acted as controls. At postmortem the pulmonary arteries were filled with a radio‐opaque resin before the lungs were scanned using computed tomography (CT). The 3D reconstructed images were analyzed based on vascular branching hierarchy using the software Avizo 2020.2. DH significantly reduced median number of arteries (2,579 (8440) versus 576 (442), p = .017), artery numbers per arterial generation, mean total arterial volume (43.5 ± 8.4 vs. 19.9 ± 3.1 μl, p = .020) and mean total arterial cross‐sectional area (82.5 ± 2.3 vs. 28.2 ± 6.2 mm2, p =.036). Mean arterial radius was increased in DH kittens between the eighth and sixth branching generation and mean arterial length between the sixth and 28th branching generation. A DH in kittens resulted in threefold reduction in pulmonary arterial cross‐sectional area, primarily due to reduced arterial branching. Thus, the reduction in arterial cross‐sectional area could be a major contributor to pulmonary hypertension infants with CDH.

Funder

Australian Research Council

National Health and Medical Research Council

ZonMw

Publisher

Wiley

Subject

Ecology, Evolution, Behavior and Systematics,Histology,Biotechnology,Anatomy

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