Abstract 5058: Glucose OxidationStimulation Affords Dramatic Protection Against in vivo Myocardial Ischemia Reperfusion Injury
Bibliographic record
Abstract
During reperfusion of the ischemic myocardium, fatty acid oxidation rates quickly recover, while glucose oxidation rates remain low, which decreases cardiac efficiency during reperfusion. Malonyl CoA decarboxylase (MCD) degrades malonyl CoA and increases fatty acid oxidation by relieving malonyl CoA-dependent inhibition of carnitine palmitoyl transferase-1. Studies have shown that MCD inhibition improves reperfusion recovery of ischemic hearts ex vivo by reducing fatty acid oxidation rates and increasing glucose oxidation rates. The objective of this study was to determine whether MCD inhibition would translate into a reduction in infarct size. Wild Type (WT, n = 7) or MCD deficient (MCD−/−, n = 7) mice had their left anterior descending coronary artery ligated for 30 min followed by 24 hr reperfusion. MCD−/− mice demonstrated a dramatic reduction in infarct size compared to WT mice (10.8±3.8 vs. 39.5±4.7 % of area at risk, P < 0.05) despite similar areas at risk (53 vs. 52 % of left ventricle). Furthermore, malonyl CoA levels were higher in the area at risk of hearts from MCD−/− mice (3.9±0.7 vs. 1.9±0.5 nmol/g wet weight, P < 0.05). Because the protection against ex vivo ischemia/reperfusion injury in MCD−/− mice was associated with increased myocardial glucose oxidation rates, secondary to an inhibition of fatty acid oxidation, we next determined whether direct stimulation of pyruvate dehydrogenase (PDH) and subsequent glucose oxidation would also afford protection against myocardial infarction. Infusion of the PDH activator, dichloroacetate (100 mg/kg intraperitoneal injection, followed by hourly injections of 50 mg/kg for the 24 hr duration of reperfusion), demonstrated significant protection against myocardial infarction (36.4±2.4 vs. 50.3±3.2 % of area at risk, P < 0.05). We demonstrate that MCD inhibition is beneficial against ischemia/reperfusion injury, possibly due to its effects on glucose oxidation stimulation, validating the optimization of myocardial metabolism as a novel therapy for ischemic heart disease.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".