Prolonged mechanical ventilation in humans impairs diaphragm muscle fiber contractility and reduces myofilament protein expression
Bibliographic record
Abstract
In this study, we assessed diaphragm myofilament contractility and myofilament protein levels in humans undergoing prolonged MV. Diaphragm biopsies were obtained from 10 control subjects and 8 brain-dead organ donors. MV durations for the two groups averaged 1.1 and 49.3 hours, respectively. Specific active and passive forces produced by diaphragm myofibrils were measured with atomic force cantilevers. Rate of force development (Kact), the rate of force re-development after a shortening-stretching protocol (Ktr), and the rate of relaxation (Krel) in fully activated myofibrils were also assessed. Protein levels of myosin, troponin I, T, and C, tropomyosin and sarcomeric actin were measured with SDS immunoblotting. Titin and nebulin protein levels were measured with agarose electrophoresis. Prolonged MV was associated with significant decline in active and passive forces produced by diaphragm myofibrils. The decrease in active force was accompanied by a decrease in the Kact, Ktr and Krel, suggesting an impairment of myosin cross-bridge kinetics. Prolonged MV significantly reduced troponin T and tropomyosin protein levels. Titin levels declined in three diaphragm samples obtained from brain-dead organ donors. Nebulin protein levels were similar to control subjects. We conclude that prolonged MV in humans triggers significant impairment of diaphragm myofilament contractility and this dysfunction is mediated through impaired myosin-actin interactions. The mechanisms behind this impairment remain unclear but we propose that it may be due to selective degradation of myofilament proteins including troponin T and tropomyosin that regulate this interaction.
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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 | 0.000 | 0.000 |
| 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".