Stimulation of glucose oxidation protects against acute myocardial infarction and reperfusion injury
Why this work is in the frame
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Bibliographic record
Abstract
AIMS: During reperfusion of the ischaemic myocardium, fatty acid oxidation rates quickly recover, while glucose oxidation rates remain depressed. Direct stimulation of glucose oxidation via activation of pyruvate dehydrogenase (PDH), or secondary to an inhibition of malonyl CoA decarboxylase (MCD), improves cardiac functional recovery during reperfusion following ischaemia. However, the effects of such interventions on the evolution of myocardial infarction are unknown. The purpose of this study was to determine whether infarct size is decreased in response to increased glucose oxidation. METHODS AND RESULTS: In vivo, direct stimulation of PDH in mice with the PDH kinase (PDHK) inhibitor, dichloroacetate, significantly decreased infarct size following temporary ligation of the left anterior descending coronary artery. These results were recapitulated in PDHK 4-deficient (PDHK4-/-) mice, which have enhanced myocardial PDH activity. These interventions also protected against ischaemia/reperfusion injury in the working heart, and dichloroacetate failed to protect in PDHK4-/- mice. In addition, there was a dramatic reduction in the infarct size in malonyl CoA decarboxylase-deficient (MCD-/-) mice, in which glucose oxidation rates are enhanced (secondary to an inhibition of fatty acid oxidation) relative to their wild-type littermates (10.8 ± 3.8 vs. 39.5 ± 4.7%). This cardioprotective effect in MCD-/- mice was associated with increased PDH activity in the ischaemic area at risk (1.89 ± 0.18 vs. 1.52 ± 0.05 μmol/g wet weight/min). CONCLUSION: These findings demonstrate that stimulating glucose oxidation via targeting either PDH or MCD decreases the infarct size, validating the concept that optimizing myocardial metabolism is a novel therapy for ischaemic heart disease.
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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 | 0.005 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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