Cardiac index and cardiac output

Where it participates (unsigned role)

1. In thirteen patients with severe pulmonary hypertension the decrease in pulmonary vascular resistance was similar with inhaled nitric oxide at 19% and sildenafil at 27% while the combination was more effective than inhaled nitric oxide alone at 32%, sildenafil and the combination increased cardiac index by 17% whereas inhaled nitric oxide did not, inhaled nitric oxide increased whereas sildenafil tended to decrease pulmonary capillary wedge pressure, systemic arterial pressure was similar among groups and did not decrease, and cyclic GMP rose similarly with each agent while the combination raised it synergistically.

   Sildenafil → Pulmonary vascular resistance source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/sildenafil-research/12021227.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0", "start_char": 0, "end_char": 1828, "text_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0"}

   experimental_model

   Acute haemodynamic study in thirteen consecutive patients referred for transplantation assessment or therapy guidance

   exposure

   Inhaled nitric oxide at 80 parts per million, oral sildenafil 75 milligrams, and the combination, with serum cyclic GMP measured

   limitations

   Compares the drug directly against the reference selective pulmonary vasodilator in the same patients and measures the messenger. Thirteen patients and a single dose.

   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

   An oral tablet matched inhaled nitric oxide as a selective lung vasodilator and, unlike it, raised cardiac output.

   primary_references

   [sil-p12021227] Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. (2002). https://pubmed.ncbi.nlm.nih.gov/12021227/ DOI: 10.1161/01.cir.0000016641.12984.dc

   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 535–546

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute haemodynamic study in thirteen consecutive patients referred for transplantation assessment or therapy guidance · source_derived_draft · unverified_draft

   ### sil-as-selective-as-inhaled-no In thirteen patients with severe pulmonary hypertension the decrease in pulmonary vascular resistance was similar with inhaled nitric oxide at 19% and sildenafil at 27% while the combination was more effective than inhaled nitric oxide alone at 32%, sildenafil and the combination increased cardiac index by 17% whereas inhaled nitric oxide did not, inhaled nitric oxide increased whereas sildenafil tended to decrease pulmonary capillary wedge pressure, systemic arterial pressure was similar among groups and did not decrease, and cyclic GMP rose similarly with each agent while the combination raised it synergistically. 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: An oral tablet matched inhaled nitric oxide as a selective lung vasodilator and, unlike it, raised cardiac output. organism: Human tissue_or_cell_type: Pulmonary circulation experimental_model: Acute haemodynamic study in thirteen consecutive patients referred for transplantation assessment or therapy guidance limitations: Compares the drug directly against the reference selective pulmonary vasodilator in the same patients and measures the messenger. Thirteen patients and a single dose. exposure: Inhaled nitric oxide at 80 parts per million, oral sildenafil 75 milligrams, and the combination, with serum cyclic GMP measured evidence_span: {"source_cache": "artifacts/sildenafil-research/12021227.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0", "start_char": 0, "end_char": 1828, "text_sha256": "69f5687bcf1bb0fcf9d96eb7fe2f756ccfe3bbdd76af85560110b985245947e0"} [sil-p12021227] Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. (2002). https://pubmed.ncbi.nlm.nih.gov/12021227/ DOI: 10.1161/01.cir.0000016641.12984.dc

   Complete structured claim and evidence

2. 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

3. At low altitude under 10 percent inspired oxygen sildenafil 50 milligrams significantly increased arterial oxygen saturation during exercise, reduced systolic pulmonary artery pressure at rest and during exercise, and increased maximum workload from 130.6 to 172.5 watts and maximum cardiac output, while at Mount Everest base camp it had no effect on arterial oxygen saturation but still reduced systolic pulmonary artery pressure at rest and during exercise and increased maximum workload and cardiac output, exacerbating existing headache in two participants.

   Sildenafil → Maximum workload on cycle ergometry source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/sildenafil-research/15289213.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136", "start_char": 0, "end_char": 2481, "text_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136"}

   experimental_model

   Randomised double-blind placebo-controlled crossover study in fourteen mountaineers at low altitude under hypoxic gas and at Mount Everest base camp

   exposure

   Oral sildenafil 50 milligrams, with systolic pulmonary artery pressure, cardiac output and arterial oxygen saturation at rest and at maximum exercise

   limitations

   A crossover design carried out in two settings including genuine altitude. Fourteen participants, and the study did not examine normoxic exercise tolerance.

   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

   By lowering the pressure the lung raises against low oxygen, it let people work substantially harder.

   primary_references

   [sil-p15289213] Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. (2004). https://pubmed.ncbi.nlm.nih.gov/15289213/ DOI: 10.7326/0003-4819-141-3-200408030-00005

   tissue_or_cell_type

   Pulmonary circulation and 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 587–598

   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 study in fourteen mountaineers at low altitude under hypoxic gas and at Mount Everest base camp · source_derived_draft · unverified_draft

   ### sil-raises-exercise-capacity-in-hypoxia At low altitude under 10 percent inspired oxygen sildenafil 50 milligrams significantly increased arterial oxygen saturation during exercise, reduced systolic pulmonary artery pressure at rest and during exercise, and increased maximum workload from 130.6 to 172.5 watts and maximum cardiac output, while at Mount Everest base camp it had no effect on arterial oxygen saturation but still reduced systolic pulmonary artery pressure at rest and during exercise and increased maximum workload and cardiac output, exacerbating existing headache in two participants. 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: By lowering the pressure the lung raises against low oxygen, it let people work substantially harder. organism: Human tissue_or_cell_type: Pulmonary circulation and exercise capacity experimental_model: Randomised double-blind placebo-controlled crossover study in fourteen mountaineers at low altitude under hypoxic gas and at Mount Everest base camp limitations: A crossover design carried out in two settings including genuine altitude. Fourteen participants, and the study did not examine normoxic exercise tolerance. exposure: Oral sildenafil 50 milligrams, with systolic pulmonary artery pressure, cardiac output and arterial oxygen saturation at rest and at maximum exercise evidence_span: {"source_cache": "artifacts/sildenafil-research/15289213.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136", "start_char": 0, "end_char": 2481, "text_sha256": "9767ed0c1022cee4fb74a2caef80b8ac9afd40077da8b6d1651fe0e631fde136"} [sil-p15289213] Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. (2004). https://pubmed.ncbi.nlm.nih.gov/15289213/ DOI: 10.7326/0003-4819-141-3-200408030-00005

   Complete structured claim and evidence