Phospholipid Lysophosphatidylcholine as a Metabolic Trigger and HERG as an Ionic Pathway for Extracellular K<sup>+</sup> Accumulation and “Short QT Syndrome” in Acute Myocardial Ischemia
Bibliographic record
Abstract
The most profound abnormalities during acute myocardial ischemia are extracellular K(+) accumulation ([K(+)](o)- upward arrow) and shortening of action potential duration or QT interval (APD- downward arrow or QT- downward arrow), which are pivotal in the genesis of ischemic arrhythmias and sudden cardiac death. The ionic mechanisms however remained obscured. We performed studies in a rabbit model of acute global myocardial ischemia in order to explore ionic and metabolic mechanisms for ischemic [K(+)](o)- upward arrow and QT- downward arrow. Exogenous 1-palmitoyl-lysophosphatidylcholine (LPC-16) mimicked the low-perfusion ischemia to produce significant [K(+)](o)- upward arrow and QT- downward arrow. The [K(+)](o)- upward arrow and QT- downward arrow induced by either LPC-16 or ischemia were prevented by dofetilide, a blocker of rapid delayed rectifier K(+) current (I(Kr)), but not by blockers for other K(+) channels. Consistently, dofetilide efficiently abolished the ventricular tachy-arrhythmias induced by ischemia or LPC-16. LPC-16 remarkably shortened APD and enhanced the function of I(Kr) and HERG (the pore-forming subunit of I(Kr)). The effects of LPC-16 manifested with shorter APD (faster repolarization rate) and at more negative potential (membrane repolarization). Dofetilide abolished the I(Kr)/HERG enhancing and APD shortening effects of LPC-16. Our results suggest that LPC-16 accumulation/HERG enhancement may be a link between metabolic trigger and ionic pathway for ischemic [K(+)](o)- upward arrow and QTc- downward arrow. This represents the first documentation of I(Kr)/HERG as the ionic mechanism in ischemic [K(+)](o)- upward arrow and QTc- downward arrow. Inhibition of LPC-16 production and accumulation and/or of I(Kr)/HERG may be a promising therapeutic strategy to attenuate the incidence of lethal arrhythmias associated with 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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".