Impact of aging on the response to mechanical ventilation in mice
Bibliographic record
Abstract
Mechanical ventilation is a critical, life-saving therapy that can also negatively impact the lung by affecting edema formation, surfactant metabolism and function, and the release of inflammatory mediators. Outcomes in elderly patients requiring ventilation are generally worse than in younger patients; however, the impact that age has on the response to mechanical ventilation has not been explored in detail. We hypothesized that aged mice would have an altered response to mechanical ventilation compared to young mice.To test our hypothesis male mice of 2-3 (young) and 22-23 (aged) months of age were mechanically ventilated at a tidal volume of 20ml/kg for 3 hours. Subsequently, lungs were lavaged and the lavage fluid was analyzed for total protein and IgM to assess edema, surfactant amounts and function, and the concentration of inflammatory mediators. Frozen lung tissue was used for qPCR analysis of inflammatory mediators. Separate cohorts of young and aged mice were used as non-ventilated controls.Our results showed that protein and IgM concentrations in the lavage fluid were significantly higher in aged-ventilated as compared to the young-ventilated group. Although surfactant levels were similar between young and aged mice, the function of the surfactant was significantly impaired in aged-ventilated as compared to the young-ventilated group. The lavage concentrations of pro-inflammatory mediators (IL6, IL1β, CXCL1, CXCL2, and CCL2) were significant lower in aged-ventilated as compared to the young-ventilated mice, with mRNA levels following a similar pattern. Further, the MRNA levels of inflammatory mediators in non-ventilated animals were markedly lower than in ventilated animals.In conclusion, the response to mechanical ventilation is affected by age. Since surfactant impairment and edema formation contribute to the severity of lung injury, the data for these outcomes suggest a more harmful response in the aged animals. Overwhelming inflammation has also been associated with augmented lung injury. The reduced level of inflammation in the aged mice implies altered inflammatory responses; the impact of this on overall outcomes during mechanical ventilation requires further investigation. Canadian Institute of Health Research; Western University This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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 | 0.001 | 0.001 |
| 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".