Component

Six-minute walk distance

Distance walked in six minutes, the primary endpoint in the pulmonary arterial hypertension trial.

3 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. In ten patients with pulmonary hypertension either primary or related to previous left-to-right shunts, thromboembolism or interstitial lung disease and poorly controlled on conventional therapy, sildenafil 25 milligrams eight hourly for two weeks was associated compared with placebo with improved exercise tolerance on the six-minute walk test at 266.67 against 170 metres, a decrease in modified Borg dyspnea score from 5.11 to 3.56, a decrease in Doppler-estimated pulmonary artery systolic pressure from 75.33 to 55.33 millimetres of mercury, and improvement in New York Heart Association class in two patients, with no significant changes in heart rate or blood pressure.

    Sildenafil → Six-minute walk distance source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/12760589.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5", "start_char": 0, "end_char": 2507, "text_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5"}
    experimental_model
    Randomised double-blind placebo-controlled crossover trial in ten consecutive patients poorly controlled on conventional therapy
    exposure
    Sildenafil 25 milligrams every eight hours or matching placebo for two weeks each with a two-week run-in between
    limitations
    Ten patients of mixed aetiology, with pulmonary artery pressure estimated by echo Doppler rather than catheter, and a two-week exposure.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human
    plain_language
    Two weeks of tablets let these patients walk nearly a hundred metres further and dropped the pressure in the lung.
    primary_references
    [sil-p12760589] The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12760589/
    tissue_or_cell_type
    Pulmonary circulation

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 574–585

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised double-blind placebo-controlled crossover trial in ten consecutive patients poorly controlled on conventional therapy · source_derived_draft · unverified_draft

    ### sil-improves-walking-and-pressure In ten patients with pulmonary hypertension either primary or related to previous left-to-right shunts, thromboembolism or interstitial lung disease and poorly controlled on conventional therapy, sildenafil 25 milligrams eight hourly for two weeks was associated compared with placebo with improved exercise tolerance on the six-minute walk test at 266.67 against 170 metres, a decrease in modified Borg dyspnea score from 5.11 to 3.56, a decrease in Doppler-estimated pulmonary artery systolic pressure from 75.33 to 55.33 millimetres of mercury, and improvement in New York Heart Association class in two patients, with no significant changes in heart rate or blood pressure. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: Two weeks of tablets let these patients walk nearly a hundred metres further and dropped the pressure in the lung. organism: Human tissue_or_cell_type: Pulmonary circulation experimental_model: Randomised double-blind placebo-controlled crossover trial in ten consecutive patients poorly controlled on conventional therapy limitations: Ten patients of mixed aetiology, with pulmonary artery pressure estimated by echo Doppler rather than catheter, and a two-week exposure. exposure: Sildenafil 25 milligrams every eight hours or matching placebo for two weeks each with a two-week run-in between evidence_span: {"source_cache": "artifacts/sildenafil-research/12760589.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5", "start_char": 0, "end_char": 2507, "text_sha256": "bca7bee4050068cd35e6f9f10a8de3c3a4505b4682eef9b8f91126ac1dbf38e5"} [sil-p12760589] The efficacy and tolerability of sildenafil in patients with moderate-to-severe pulmonary hypertension. (2003). https://pubmed.ncbi.nlm.nih.gov/12760589/
    Complete structured claim and evidence

  2. Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.

    Tadalafil → Six-minute walk distance source_derived_draftungraded
    Experimental context and source evidence
    duration
    16 weeks, double-blind placebo-controlled
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan
    exposure
    Tadalafil 2.5, 10, 20 or 40 mg once daily against placebo
    limitations
    The treatment effect was 44 metres in bosentan-naive patients and 23 metres with confidence intervals crossing zero in those already on bosentan, so the benefit on top of existing endothelin blockade was not established here. PubMed records an erratum for this paper without a resolvable identifier, so the erratum was not read and it is not known whether it altered these figures.
    organism
    405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan
    plain_language
    Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance.
    primary_references
    Tadalafil therapy for pulmonary arterial hypertension. (2009). https://pubmed.ncbi.nlm.nih.gov/19470885/ DOI: 10.1161/CIRCULATIONAHA.108.839274
    route
    Oral
    tissue
    Six-minute walk distance, WHO functional class and clinical worsening

    Tadalafil: PDE5 occupancy, the cGMP route and three measured endpoints (2026-09-22) · lines 100–109

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata. Two references carry an unresolvable erratum and are recorded as corrected. Study-specific doses, effect sizes and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

    ## tadalafil-six-minute-walk-in-pulmonary-arterial-hypertension Tadalafil increased six-minute walk distance in a dose-dependent manner in pulmonary arterial hypertension, with a mean placebo-corrected effect of 33 metres, and only the 40 mg dose met the prespecified level of statistical significance. Model/species: 405 patients with idiopathic or associated pulmonary arterial hypertension, treatment-naive or on background bosentan Tissue/system: Six-minute walk distance, WHO functional class and clinical worsening Exposure: Tadalafil 2.5, 10, 20 or 40 mg once daily against placebo Route: Oral Duration: 16 weeks, double-blind placebo-controlled Limits: The treatment effect was 44 metres in bosentan-naive patients and 23 metres with confidence intervals crossing zero in those already on bosentan, so the benefit on top of existing endothelin blockade was not established here. PubMed records an erratum for this paper without a resolvable identifier, so the erratum was not read and it is not known whether it altered these figures. Primary reference: Tadalafil therapy for pulmonary arterial hypertension. (2009). https://pubmed.ncbi.nlm.nih.gov/19470885/ DOI: 10.1161/CIRCULATIONAHA.108.839274 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Among 216 patients with heart failure and preserved ejection fraction randomised to sildenafil or placebo for 24 weeks, median changes in peak oxygen consumption were not significantly different with a mean between-group difference of 0.01 millilitres per kilogram per minute, the mean clinical status rank score was not significantly different at 95.8 for placebo and 94.2 for sildenafil, and changes in six-minute walk distance were not significantly different, with serious adverse events in 16% of placebo and 22% of sildenafil patients.

    Sildenafil → Peak oxygen consumption source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/sildenafil-research/23478662.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "563c3c4bab090bd15f4627c45776c1b7cba040d7532cd85102d059753df3f8d1", "start_char": 0, "end_char": 3109, "text_sha256": "563c3c4bab090bd15f4627c45776c1b7cba040d7532cd85102d059753df3f8d1"}
    experimental_model
    Multicentre double-blind placebo-controlled randomised trial in 216 outpatients with heart failure and preserved ejection fraction
    exposure
    Sildenafil 20 milligrams three times daily for 12 weeks then 60 milligrams three times daily for 12 weeks
    limitations
    An adequately powered randomised trial with an objective primary endpoint, reported as fully negative. Its participants had elevated filling pressures and pulmonary artery systolic pressure of 41 millimetres of mercury, so the target population was appropriate.
    nutrient_topic
    Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. · Sildenafil
    organism
    Human
    plain_language
    In a proper trial in the condition the animal work pointed at, the drug did nothing at all.
    primary_references
    [sil-p23478662] Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. (2013). https://pubmed.ncbi.nlm.nih.gov/23478662/ DOI: 10.1001/jama.2013.2024
    tissue_or_cell_type
    Cardiopulmonary exercise capacity

    Sildenafil: the enzyme it occupies instead of the substrate, why it cannot start a signal it can only preserve, the organic nitrate interaction that follows from that, the homologous retinal enzyme ten-fold away, and the pulmonary circulation where the same mechanism became a second indication (2026-09-22) · lines 626–637

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicentre double-blind placebo-controlled randomised trial in 216 outpatients with heart failure and preserved ejection fraction · source_derived_draft · unverified_draft

    ### sil-no-benefit-in-hfpef Among 216 patients with heart failure and preserved ejection fraction randomised to sildenafil or placebo for 24 weeks, median changes in peak oxygen consumption were not significantly different with a mean between-group difference of 0.01 millilitres per kilogram per minute, the mean clinical status rank score was not significantly different at 95.8 for placebo and 94.2 for sildenafil, and changes in six-minute walk distance were not significantly different, with serious adverse events in 16% of placebo and 22% of sildenafil patients. Condition category: normal nutrient_topic: Sildenafil research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from its N-desmethyl metabolite and its target enzyme from the homologous retinal PDE6. plain_language: In a proper trial in the condition the animal work pointed at, the drug did nothing at all. organism: Human tissue_or_cell_type: Cardiopulmonary exercise capacity experimental_model: Multicentre double-blind placebo-controlled randomised trial in 216 outpatients with heart failure and preserved ejection fraction limitations: An adequately powered randomised trial with an objective primary endpoint, reported as fully negative. Its participants had elevated filling pressures and pulmonary artery systolic pressure of 41 millimetres of mercury, so the target population was appropriate. exposure: Sildenafil 20 milligrams three times daily for 12 weeks then 60 milligrams three times daily for 12 weeks evidence_span: {"source_cache": "artifacts/sildenafil-research/23478662.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "563c3c4bab090bd15f4627c45776c1b7cba040d7532cd85102d059753df3f8d1", "start_char": 0, "end_char": 3109, "text_sha256": "563c3c4bab090bd15f4627c45776c1b7cba040d7532cd85102d059753df3f8d1"} [sil-p23478662] Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. (2013). https://pubmed.ncbi.nlm.nih.gov/23478662/ DOI: 10.1001/jama.2013.2024
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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