Song, Y and Dahl, M and Leavitt, W and Alvord, J and Bradford, CY and Albertine, KH and Pillow, JJ, Vitamin A protects the preterm lamb diaphragm against adverse effects of mechanical ventilation, Frontiers in Physiology, 9 Article 1119. ISSN 1664-042X (2018) [Refereed Article]
Copyright 2018 Song, Dahl, Leavitt, Alvord, Bradford, Albertine and Pillow. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Methods: Preterm lambs delivered operatively at ∼131 days gestation (full gestation: 150 days) received respiratory support by synchronized intermittent mandatory ventilation for 3 days. Lambs in the treated group received daily (24 h) enteral doses of 2500 IU/kg/day vitamin A combined with 250 IU/kg/day retinoic acid (VARA) during MV, while MV control lambs received saline. Unventilated fetal reference lambs were euthanized at birth, without being allowed to breathe. The fetal diaphragm was collected to quantify mRNA levels of myosin heavy chain (MHC) isoforms, atrophy genes, antioxidant genes, and pro-inflammatory genes; to determine ubiquitin proteasome pathway activity; to measure the abundance of protein carbonyl, and to investigate metabolic signaling.
Results: Postnatal MV significantly decreased expression level of the neonatal MHC gene but increased expression level of MHC IIx mRNA level (p < 0.05). Proteasome activity increased after 3 days MV, accompanied by increased MuRF1 mRNA level and accumulated protein carbonyl abundance. VARA supplementation decreased proteasome activity and FOXO1 signaling, down-regulated MuRF1 expression, and reduced reactive oxidant production.
Conclusion: These findings suggest that 3 days of MV results in abnormal myofibrillar composition, activation of the proteolytic pathway, and oxidative injury of diaphragms in mechanically ventilated preterm lambs. Daily enteral VARA protects the preterm diaphragm from these adverse effects.
|Item Type:||Refereed Article|
|Keywords:||BPD, VIDD, bronchopulmonary dysplasia, disuse atrophy, retinoids, retinol, ventilator-induced diaphragm dysfunction|
|Research Division:||Biological Sciences|
|Research Group:||Biochemistry and Cell Biology|
|Research Field:||Signal Transduction|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Respiratory System and Diseases (incl. Asthma)|
|UTAS Author:||Song, Y (Dr Yong Song)|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||1 View Download Statistics|
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