Antiarrhythmic effects of Na‐H exchange inhibition
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Bibliographic record
Abstract
Abstract The sodium–hydrogen exchange (NHE), which extrudes protons for concomitant sodium influx, represents the primary mechanism by which the cardiac cell regulates its pH, particularly under excessive proton production. Despite this critical role, NHE, which is activated during both ischemia as well as reperfusion, has been shown to be involved in a paradoxical induction of cell injury. The mechanism for this is closely coupled to excessive sodium influx, which cannot be corrected because of ischemia‐induced inhibition of the sodium–potassium ATPase, the major pathway for sodium removal. This results in elevation in intracellular calcium concentrations through sodium–calcium exchange. Although seven NHE isoforms have thus far been identified (five cell membrane, two intracellular), the one subtype, termed NHE‐1, is the predominant isoform in the mammalian myocardium. NHE‐1‐specific inhibitors that have recently been developed, some of which are in clinical trials, have extensively demonstrated protection against ischemic and reperfusion injury as evidenced by improved function and infarct size reduction. In addition, virtually all NHE‐1 inhibitors have been demonstrated to be effective antiarrhythmic agents, and in some studies more so than classic antiarrhythmic drugs. For example, a number of studies have shown that NHE‐1 inhibitors markedly attenuate ischemia‐induced arrhythmias and can totally abolish reperfusion‐induced ventricular fibrillation. NHE‐1 inhibitors can also produce spontaneous defibrillation in a model of electrically induced cardiac arrest. As NHE is an electroneutral system, its inhibition does not directly affect cardiac electrical activity, and therefore the beneficial effects against arrhythmias likely reflect a response secondary to cardiac tissue preservation. Irrespective of precise mechanisms, NHE‐1 inhibition appears to represent an effective antiarrhythmic approach in addition to its well‐established ability to protect the ischemic and reperfused myocardium. Drug Dev. Res. 55:22–28, 2002. © 2002 Wiley‐Liss, Inc.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it