Therapeutic hypercapnia prevents pulmonary hypertension in rats with bleomycin-induced chronic neonatal lung injury
Bibliographic record
Abstract
Bleomycin (BLEO)-induced chronic neonatal lung injury (CNLI) is characterized by severe inflammation, arrest of lung development and pulmonary hypertension (PHT), in common with severe bronchopulmonary dysplasia. Chronic exposure to elevated concentrations of CO 2 (hypercapnia) may limit lung inflammation. Objectives: To examine the preventive effects of moderate (MH) or severe hypercapnia (SH) on BLEO-induced CNLI. Methods: Rat pups received BLEO (1 mg/kg/d i.p.) or saline vehicle from postnatal days 1-14 while being exposed to FiCO 2 0.05 (PaCO 2 70 mmHg; MH), FiCO 2 0.07 (PaCO 2 90 mmHg; SH) or normocapnia (NC). Inflammation was assessed by tissue counts of immunoreactive macrophages (CD68) and neutrophils (MPO). PHT was assessed by echo-Doppler measurement of pulmonary vascular resistance (PVR), right ventricle (RV)/left ventricle+septum (LV+S) weight ratio and percentage medial wall thickness (%MWT) of pulmonary resistance arteries. Markers of lung development included weight, mean linear intercept, tissue fraction, secondary crest and peripheral vessel counts. Results: SH, but not MH, attenuated BLEO-induced macrophage influx and prevented PHT, as evidenced by normalized PVR and significantly (p<0.01 vs. BLEO+NC) decreased RV/LV+S and%MWT. Neither SH nor MH affected BLEO-induced neutrophil influx, inhibited lung growth, septal thinning, impaired alveolarization or pruning of peripheral blood vessels. Conclusions: SH prevented PHT, which we speculate was the result, in major part, of inhibited macrophage influx. Neither influx of neutrophils nor pruning of peripheral arteries appeared to contribute significantly to PHT in BLEO-mediated CNLI. Funded by the CIHR.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".