Active transepithelial Cl <sup>−</sup> ‐secretion promotes hydrostatic lung edema
Bibliographic record
Abstract
Hydrostatic lung edema evolves from increased fluid filtration and inhibition of epithelial Na + channels (ENaC) that facilitate alveolar fluid clearance. Recently, we identified alveolar fluid secretion (AFS) as new key component in edema formation. Here, we tested whether Cl − secretion via cystic fibrosis transmemberane conductance regulator (CFTR) and Na + ‐K + ‐Cl − cotransporter 1 (NKCC1) may mediate AFS at elevated left atrial pressure (P LA ) and may be induced by inhibition of ENaC. In isolated lungs, we quantified AFS by a double indicator dilution technique, and transepithelial Cl − flux by radionuclide tracing and alveolar Cl − imaging. P LA elevation induced lung edema and AFS that coincided with transepithelial Cl − secretion and alveolar Cl − influx. These effects were blocked by inhibitors of CFTR, NKCC or Na + ‐K + ‐ATPase, and CFTR −/− mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride at physiological P LA induced AFS and Cl − secretion that were again CFTR‐, NKCC‐ and Na + ‐K + ‐ ATPase dependent. We conclude that transepithelial Cl − and fluid flux reverse from absorptive to secretory mode at hydrostatic stress as a result of ENaC inhibition, and are mediated by NKCC and CFTR.
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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 | 0.000 | 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 | 0.000 | 0.000 |
| 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".