Long-term effects of intrauterine growth restriction on cardiac metabolism and susceptibility to ischaemia/reperfusion
Why this work is in the frame
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Bibliographic record
Abstract
AIMS: Adult offspring who are born intrauterine growth restricted (IUGR) are at risk of developing cardiovascular diseases during adulthood. Additionally, several cardiac diseases are associated with changes in myocardial energy metabolism. However, the potential long-term effects of being born IUGR on cardiac energetics are unknown. The aim of this study was to assess the long-term effect of IUGR on cardiac performance and energy metabolism under aerobic conditions and after ischaemia/reperfusion (IR) injury. METHODS AND RESULTS: To induce IUGR, pregnant Sprague-Dawley rats were randomly assigned to hypoxic (11.5% O(2)) or control (21% O(2)) environments from day 15 to 21 of pregnancy. Cardiac susceptibility to IR was evaluated in male and female offspring at 4 (young-adult) or 12 (ageing) months of age using isolated working hearts. Cardiac production of energy was evaluated using radiolabelled substrates. Both male and female IUGR offspring exhibited an increased susceptibility to IR injury compared with controls (P< 0.05) as well as an increased post-ischaemic production of protons (P< 0.001) secondary to a mismatch between myocardial glycolysis and glucose oxidation rates. Moreover, offspring born IUGR exhibited an increased myocardial production of acetyl-CoA during reperfusion. The mismatch between energy production and cardiac performance indicates that in IUGR offspring, cardiac efficiency during reperfusion was decreased relative to controls. CONCLUSION: Our results suggest that hypoxia-induced IUGR has long-term effects on cardiac susceptibility to IR injury that are independent of sex and age. Moreover, we identified a mismatch in glucose metabolism, leading to proton accumulation in the post-ischaemic myocardium of offspring born IUGR as a potential mechanism involved.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it