Neurophysiological Mechanisms of Exertional Dyspnea in Patient’s Post-Pulmonary Embolism: The Effect of Inhaled Nitric Oxide
Bibliographic record
Abstract
Following pulmonary embolism (PE), up to a third of patients develop persistent activity-related dyspnea, even in those without chronic thromboembolic pulmonary hypertension (CTEPH). It has been shown that heightened exertional dyspnea in patients post-PE (without CTEPH) is linked to greater inspiratory neural drive (IND) during exercise. The heightened IND, in turn, is secondary to increased physiological dead space (VD/VT) and greater ventilatory requirements for CO2 (VE/VCO2). The reasons for the increased VD/VT and VE/VCO2 are unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Thus, the current study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower exertional IND and dyspnea, and improve exercise endurance in patients post-PE. In turn, the reduced IND and dyspnea would be linked to reductions in VD/VT and VE/VCO2. In this randomized, double-blind, placebo-controlled crossover study, 14 clinically stable patients with chronic activity related dyspnea post-PE (without evidence of PH) completed symptom-limited constant work rate cycle exercise tests while breathing iNO (40 ppm) or placebo (21% O2), on separate days. IND (assessed by diaphragm electromyography), VD/VT and VE/VCO2 (expired and arterialized blood gas), and dyspnea intensity (modified Borg 0-10 scale) were compared throughout exercise. At rest, right-ventricular systolic pressure (RVSP) with placebo or iNO was estimated by echocardiography. At the highest individual standardized exercise time (5.8±2.0 min), iNO decreased VD/VT (0.22±0.09 vs 0.27±0.07, p=0.02), VE/VCO2 (33.0±3.5 vs 34.5±3.8 units, p=0.04), IND (48.8±10.3 vs 57.6±11.8 %, p=0.02) and dyspnea intensity (3.0±1.0 vs 4.0±1.4 Borg units, p<0.01), compared with placebo. Throughout exercise, estimated alveolar ventilation, O2 saturation, O2 pulse and operating lung volumes were unaffected by iNO (all p>0.05). iNO increased exercise endurance time (8.1±3.5 vs 6.5±2.3 min, p<0.001), compared with placebo. iNO reduced resting RVSP by 2.5±2.0 mmHg. iNO decreased exertional IND and dyspnea, and improved exercise endurance in patients with post-PE. The reduced IND, in turn, may be linked to decreased VD/VT and VE/VCO2, reflecting improved ventilation/perfusion. These data provide preliminary evidence of a partially reversible pulmonary vasculopathy, that contributes to dyspnea and exercise limitation in symptomatic patients post-PE. Queen’s University Spear Endowment Grant. This is the full abstract presented at the American Physiology Summit 2024 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 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 | 0.001 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".