Contribution of Protons to Post‐Ischemic Na<sup>+</sup> and Ca<sup>2+</sup> Overload and Left Ventricular Mechanical Dysfunction
Bibliographic record
Abstract
The intracellular accumulation of Na(+) and Ca(2+) plays a key role in ischemia-induced myocardial injury that may be manifest as left ventricular (LV) mechanical dysfunction, dysrhythmias, or infarction. This review considers the potential contributions of protons (H(+)) produced during ischemia as well as reperfusion to intracellular Na(+) and Ca(2+) homeostasis. ATP hydrolysis produces H(+) and the resulting intracellular acidosis directly impairs LV contractility. However, it is the accumulation of intracellular H(+) and the activation of Na(+)-dependent pH regulatory mechanisms, including the Na(+)-H(+) exchanger (NHE-1) and the Na(+)-HCO(3) (-) cotransporter, which contribute to Na(+) accumulation. Intracellular Na(+) accumulation, coupled with the NHE-1, then causes Ca(2+) overload and further LV mechanical dysfunction. As glycolysis uncoupled from glucose oxidation is an important determinant of the rate of H(+) production, factors that affect glucose metabolism, including degree of ischemia, myocardial workload, and competition from other energy substrates, are expected to influence Na(+) and Ca(2+) accumulation, and hence the recovery of post-ischemic LV mechanical function. Whereas an increase in the uncoupling of glycolysis from glucose oxidation accelerates H(+) production and worsens the recovery of LV mechanical function, inhibition of H(+) production improves recovery of post-ischemic LV mechanical function. Thus, alteration of glucose metabolism, either by inhibition of an excessive rate of glycolysis or by stimulation of glucose oxidation, is an attractive drug target to reduce H(+) production and limit Na(+) and Ca(2+) accumulation and thereby prevent post-ischemic LV dysfunction.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.004 |
| 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 | 0.001 | 0.002 |
| 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".