Associate Professor Childrens Hospital of Philadelphia Philadelphia, Pennsylvania, United States
Background: The morbidities associated with preterm birth exert enduring deleterious effects on the cardiopulmonary health of adults with a history of preterm birth. Adults born prematurely are at greater risk for heart failure compared to their full-term counterparts. This underscores the imperative for further research on long-term cardiopulmonary consequences attributable to preterm birth. Objective: Our objective was to understand the chamber specific effects in the neonatal heart exposed to early hyperoxic injury. The goal was to identify mechanisms related to altered recovery and repair mechanisms following injury to the neonatal heart. We hypothesized that neonatal hyperoxia exposure will lead to increased fibrosis and decreased micro vessel density. Design/Methods: Male and female neonatal mouse pups (C57BL6) were exposed to hyperoxia (95% FiO2) from PND 1-5 (equates to 26-36 weeks of human gestation) postnatally (Figure A) and euthanized at 10 weeks of postnatally after recovery in room air. Hearts (ventricles and atria) from mice of either sex were analyzed after H&E tissue staining (left ventricle (LV)+ Interventricular septum (IVS muscle area; Right ventricular (RV) muscle area, left atrial (LA) chamber size, right atrial (RA) chamber size; Figure B, left). Sirius Red Fast Green staining for collagen deposition (Figure B, right) and Pecam1 staining for vessel density was performed (Figure C). Atria and ventricles from male and female mice were also subjected to bulk-RNA Seq. We also performed echocardiography on room air and hyperoxia exposed mice at 10 weeks. 6-8 biological replicates were used per group for the analyses. All measurements were done using ImageJ/Fiji. Results: At 10 weeks of age, post-hyperoxia exposure, histological analysis showed increased left atrial chamber size in hyperoxia compared to room air controls (Figure D) with no effect on the other chambers of the heart. Increased left atrial size was also confirmed by echocardiographic estimation. There were no significant changes in collagen deposition between groups. Lastly, vessel density decreased in the right atria of hyperoxia exposed mice compared to controls (Figure E) with no effect in the rest of the cardiac chambers. Biological pathways related to apoptosis, unfolded protein response, and response to oxidative stress were enriched in the hyperoxia-exposed atria.
Conclusion(s): Neonatal hyperoxia exposure has a profound but differential impact on the atria and ventricles (atria>ventricles). Functional consequences of effects on the atria on cardiac function and its correlation in human preterm neonates is currently ongoing.
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