Abstract 046: Cardiac Mitochondria are Impaired After Transient Neonatal High Oxygen Exposure in a Rat Model of Prematurity-Related Condition
Bibliographic record
Abstract
The heart relies on adequate mitochondrial (mito) ATP production to match myocardial demand, mostly through oxidative phosphorylation. Preterm birth (PT) results in ex utero development of an immature myocardium and PT-born individuals represent a newly recognized group at high risk of cardiovascular diseases. Our group has shown that newborn rats exposed to high oxygen (O 2 ), mimicking PT-related conditions, develop O 2 -induced cardiomyopathy (OIC) and dysfunction later in life. However, whether mito impairments prevail in the programmed left ventricle (LV) changes associated with PT is unknown. We aimed to determine whether OIC is associated with altered LV mito characteristics in 4 wks-old rats. Male rat pups were kept with their mother in 80% O 2 (OIC) or room air (Ctrl) from days 3 to 10 of life. Results are mean±SEM; OIC vs. Ctrl are compared using t-test (n=4/group.P<0.05). At 4 wks, extracellular flux analysis of isolated LV cardiomyocytes revealed significantly decreased O 2 consumption rate in OIC (12.14±5.74 vs. 67.39±13.61 pmoles/min/ug). OIC rats show reduced LV mito copy number determined by the ratio between mito and genomic DNA (26.7±6.30 vs. 52.7±7.32), biogenesis markers Pgc1α (0.59±0.14 vs. 1.18±0.25), and citrate synthase (0.20±0.16 vs. 1.60±0.56) mRNA, and reduced Complex IV (0.66±0.15 vs. 1.26±0.09) protein expression. Gene expression (RT-PCR) of key glycolytic enzymes, hexokinase (3.34±0.59 vs. 0.88±0.39) and glucose-6-phosphate dehydrogenase (2.85±0.48 vs. 0.58±0.08) is significantly increased, indicating a shift toward glycolysis. OIC also were found to have higher LV mtROS production (7581±51 vs. 5191±99, fluorescence arbitrary units) and decreased antioxidant SOD2 protein expression (0.84±0.09 vs. 1.04±0.05). Taken together our results indicate that neonatal hyperoxia exposure leads to decreased LV mito biogenesis and function with impaired oxidative phosphorylation capacity in juvenile animals. Further studies are needed to determine the role of long-term mito dysfunction in the increased susceptibility to heart failure observed after deleterious neonatal conditions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".