The Calcium Sensitizer Levosimendan Improves Human Diaphragm Function
Bibliographic record
Abstract
RATIONALE: Acquired diaphragm muscle weakness is a key feature in several chronic conditions, including chronic obstructive pulmonary disease, congestive heart failure, and difficult weaning from mechanical ventilation. No drugs are available to improve respiratory muscle function in these patients. Recently, we have shown that the calcium sensitizer levosimendan enhances the force-generating capacity of isolated diaphragm fibers. OBJECTIVES: To investigate the effects of the calcium sensitizer levosimendan on in vivo human diaphragm function. METHODS: In a double-blind, randomized, crossover design, 30 healthy subjects performed two identical inspiratory loading tasks. After the first loading task, subjects received levosimendan (40 μg/kg bolus followed by 0.1/0.2 μg/kg/min continuous infusion) or placebo. Transdiaphragmatic pressure, diaphragm electrical activity, and their relationship (neuromechanical efficiency) were measured during loading. Magnetic phrenic nerve stimulation was performed before the first loading task and after bolus administration to assess twitch contractility. Center frequency of diaphragm electrical activity was evaluated to study the effects of levosimendan on muscle fiber conduction velocity. MEASUREMENTS AND MAIN RESULTS: The placebo group showed a 9% (P=0.01) loss of twitch contractility after loaded breathing, whereas no loss in contractility was observed in the levosimendan group. Neuro-mechanical efficiency of the diaphragm during loading improved by 21% (P<0.05) in the levosimendan group. Baseline center frequency of diaphragm electrical activity was reduced after levosimendan administration (P<0.05). CONCLUSIONS: The calcium sensitizer levosimendan improves neuromechanical efficiency and contractile function of the human diaphragm. Our findings suggest a new therapeutic approach to improve respiratory muscle function in patients with respiratory failure.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".