Tolerance to ischaemic injury in remodelled mouse hearts: less ischaemic glycogenolysis and preserved metabolic efficiency
Bibliographic record
Abstract
AIMS: Post-infarction remodelled failing hearts have reduced metabolic efficiency. Paradoxically, they have increased tolerance to further ischaemic injury. This study was designed to investigate the metabolic mechanisms that may contribute to this phenomenon and to examine the relationship between ischaemic tolerance and metabolic efficiency during post-ischaemic reperfusion. METHODS AND RESULTS: Male C57BL/6 mice were subjected to coronary artery ligation (CAL) or SHAM surgery. After 4 weeks, in vivo mechanical function was assessed by echocardiography, and then isolated working hearts were perfused in this sequence: 45 min aerobic, 15 min global no-flow ischaemia, and 30 min aerobic reperfusion. Left ventricular (LV) function, metabolic rates, and metabolic efficiency were measured. Relative to SHAM, both in vivo and in vitro CAL hearts had depressed cardiac function under aerobic conditions (45 and 36%, respectively), but they had a greater recovery of LV function during post-ischaemic reperfusion (67 vs. 49%, P < 0.05). While metabolic efficiency (LV work per ATP produced) was 50% lower during reperfusion of SHAM hearts, metabolic efficiency in CAL hearts did not decrease. During ischaemia, glycogenolysis was 28% lower in CAL hearts, indicative of lower ischaemic proton production. There were no differences in mitochondrial abundance, calcium handling proteins, or key metabolic enzymes. CONCLUSION: Compared with SHAM, remodelled CAL hearts are more tolerant to ischaemic injury and undergo no further deterioration of metabolic efficiency during reperfusion. Less glycogen utilization in CAL hearts during ischaemia may contribute to increased ischaemic tolerance by limiting ischaemic proton production that may improve ion homeostasis during early reperfusion.
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How this classification was reachedexpand
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 | 0.006 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".