Heart rate

evidence_span

{"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"}

experimental_model

Double-blind crossover drug-context trial

exposure

5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily

limitations

Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

47 hypertensive patients stable on nifedipine

plain_language

This outcome is retained separately from the blood-pressure finding.

primary_references

[melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x

tissue_or_cell_type

Ambulatory blood pressure and heart rate

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 1046–1057

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover drug-context trial · source_derived_draft · unverified_draft

### melatonin-nifedipine-heart-rate Heart rate increased by about 3.9 beats/minute during the melatonin period. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This outcome is retained separately from the blood-pressure finding. organism: 47 hypertensive patients stable on nifedipine tissue_or_cell_type: Ambulatory blood pressure and heart rate experimental_model: Double-blind crossover drug-context trial limitations: Observed drug-context effect. The authors proposed competition, but a specific transporter, CYP interaction or calcium-channel mechanism was not proven. exposure: 5 mg melatonin nightly for four weeks; nifedipine GITS 30 or 60 mg daily evidence_span: {"source_cache": "artifacts/melatonin-research/10792199.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b", "start_char": 0, "end_char": 1482, "text_sha256": "71e8d66126f1339089c1fda1bee67e6ceaf0afb4001d547741056521babf881b"} [melatonin-p10792199] Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. (2000). https://pubmed.ncbi.nlm.nih.gov/10792199/ DOI: 10.1046/j.1365-2125.2000.00195.x

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/28268688.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90c0491fa4681d112ecfc224671b763a608eeb03af4bf563955dc49ef628b851", "start_char": 0, "end_char": 1500, "text_sha256": "90c0491fa4681d112ecfc224671b763a608eeb03af4bf563955dc49ef628b851"}

experimental_model

Asphyxial cardiac arrest in rats comparing bolus injection with femoral vein infusion

exposure

Dihydrocapsaicin by bolus injection or by infusion at 0.75 mg/kg/h for four hours after cardiac arrest

limitations

Directly compares two routes of the same drug and finds the route decides whether the cardiovascular effects appear. Neurological recovery was followed for only three days.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

Injected all at once it disturbs the heart; infused slowly it does not, and the animals did better.

primary_references

[dhc-p28268688] Dihydrocapsaicin-induced hypothermia after asphyxiai cardiac arrest in rats. (2016). https://pubmed.ncbi.nlm.nih.gov/28268688/ DOI: 10.1109/embc.2016.7591082

tissue_or_cell_type

Brain and cardiovascular system

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 361–372

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Asphyxial cardiac arrest in rats comparing bolus injection with femoral vein infusion · source_derived_draft · unverified_draft

### dhc-route-decides-safety Comparing bolus injection with femoral vein infusion, cardiovascular effects were seen only with a large-dose dihydrocapsaicin bolus injection, and four-hour infusion at 0.75 mg/kg/h after cardiac arrest maintained a body temperature of about 34 degrees for at least eight hours with treated rats remaining viable, showing higher electrical activity during the first four hours and better neurological recovery over three days than normothermia rats. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: Injected all at once it disturbs the heart; infused slowly it does not, and the animals did better. organism: Rat tissue_or_cell_type: Brain and cardiovascular system experimental_model: Asphyxial cardiac arrest in rats comparing bolus injection with femoral vein infusion limitations: Directly compares two routes of the same drug and finds the route decides whether the cardiovascular effects appear. Neurological recovery was followed for only three days. exposure: Dihydrocapsaicin by bolus injection or by infusion at 0.75 mg/kg/h for four hours after cardiac arrest evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/28268688.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "90c0491fa4681d112ecfc224671b763a608eeb03af4bf563955dc49ef628b851", "start_char": 0, "end_char": 1500, "text_sha256": "90c0491fa4681d112ecfc224671b763a608eeb03af4bf563955dc49ef628b851"} [dhc-p28268688] Dihydrocapsaicin-induced hypothermia after asphyxiai cardiac arrest in rats. (2016). https://pubmed.ncbi.nlm.nih.gov/28268688/ DOI: 10.1109/embc.2016.7591082

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/

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sildenafil-research/10078539.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654", "start_char": 0, "end_char": 3999, "text_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654"}

experimental_model

Double-blind placebo-controlled crossover studies of nitrate and calcium antagonist coadministration in healthy men and men with hypertension

exposure

Sildenafil 25 milligrams three times daily with stepwise intravenous and sublingual glyceryl trinitrate, and a single 100 milligram dose with amlodipine

limitations

The design that establishes the contraindication, and the amlodipine arm is the control that shows it is specific to the shared pathway rather than additive antihypertensive effect.

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

On this drug a standard nitrate tablet dropped blood pressure four times as far.

primary_references

[sil-p10078539] Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. (1999). https://pubmed.ncbi.nlm.nih.gov/10078539/ DOI: 10.1016/s0002-9149(99)00044-2

tissue_or_cell_type

Systemic circulation

trigger_kind

biomarker_context Imported condition classification; unverified.

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 405–416

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled crossover studies of nitrate and calcium antagonist coadministration in healthy men and men with hypertension · source_derived_draft · unverified_draft

### sil-nitrate-potentiation-fourfold During treatment with sildenafil 25 milligrams three times daily subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo based on the occurrence of a greater than 25 millimetre fall in blood pressure or symptomatic hypotension, and when a 500 microgram sublingual glyceryl trinitrate tablet was administered a fourfold greater decrease in systolic blood pressure was observed during the sildenafil period than during placebo, with negligible changes in heart rate, so that administration to patients using organic nitrates in any form is contraindicated. Condition category: biomarker_context 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: On this drug a standard nitrate tablet dropped blood pressure four times as far. organism: Human tissue_or_cell_type: Systemic circulation experimental_model: Double-blind placebo-controlled crossover studies of nitrate and calcium antagonist coadministration in healthy men and men with hypertension limitations: The design that establishes the contraindication, and the amlodipine arm is the control that shows it is specific to the shared pathway rather than additive antihypertensive effect. exposure: Sildenafil 25 milligrams three times daily with stepwise intravenous and sublingual glyceryl trinitrate, and a single 100 milligram dose with amlodipine evidence_span: {"source_cache": "artifacts/sildenafil-research/10078539.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654", "start_char": 0, "end_char": 3999, "text_sha256": "469d3f90cc5be3f1c0ef247d099fa70d81aa953b8a6b33334abc38d34f346654"} [sil-p10078539] Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. (1999). https://pubmed.ncbi.nlm.nih.gov/10078539/ DOI: 10.1016/s0002-9149(99)00044-2

evidence_span

{"source_cache": "artifacts/cold-research/9202941.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c66741aac658e383d3e372a1c257db8dbcbce5e57d4dc053583181192f0c2e1", "start_char": 0, "end_char": 1846, "text_sha256": "0c66741aac658e383d3e372a1c257db8dbcbce5e57d4dc053583181192f0c2e1"}

experimental_model

Twenty subjects immersing finger, hand, or forearm and hand in 5 degrees C water

exposure

30 minutes of immersion at 5 degrees C followed by 15 minutes of recovery

limitations

The comparison of immersed areas is the point: the cardiovascular response depends on how much skin is cooled, not on the temperature alone.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

How much of you goes in the water decides what your heart and vessels do.

primary_references

[cold-p9202941] Cold induced vasodilatation and cardiovascular responses in humans during cold water immersion of various upper limb areas. (1997). https://pubmed.ncbi.nlm.nih.gov/9202941/ DOI: 10.1007/s004210050191

tissue_or_cell_type

Upper limb skin and cardiovascular system

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 221–232

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twenty subjects immersing finger, hand, or forearm and hand in 5 degrees C water · source_derived_draft · unverified_draft

### cold-civd-area-dependence Index-finger cooling produced cold-induced vasodilatation earlier than hand or forearm immersion (5.90 versus 7.95 and 9.26 minutes) and without significant cardiovascular change, whereas hand or forearm immersion produced a delayed and slower vasodilatation with bradycardia at the end of the test and a larger blood pressure rise. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: How much of you goes in the water decides what your heart and vessels do. organism: Human tissue_or_cell_type: Upper limb skin and cardiovascular system experimental_model: Twenty subjects immersing finger, hand, or forearm and hand in 5 degrees C water limitations: The comparison of immersed areas is the point: the cardiovascular response depends on how much skin is cooled, not on the temperature alone. exposure: 30 minutes of immersion at 5 degrees C followed by 15 minutes of recovery evidence_span: {"source_cache": "artifacts/cold-research/9202941.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c66741aac658e383d3e372a1c257db8dbcbce5e57d4dc053583181192f0c2e1", "start_char": 0, "end_char": 1846, "text_sha256": "0c66741aac658e383d3e372a1c257db8dbcbce5e57d4dc053583181192f0c2e1"} [cold-p9202941] Cold induced vasodilatation and cardiovascular responses in humans during cold water immersion of various upper limb areas. (1997). https://pubmed.ncbi.nlm.nih.gov/9202941/ DOI: 10.1007/s004210050191

evidence_span

{"source_cache": "artifacts/cold-research/9763650.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f007b123776a775f6672afa5075a3085c9ddb82578ad6b8984d3da95efbfd47", "start_char": 0, "end_char": 1204, "text_sha256": "0f007b123776a775f6672afa5075a3085c9ddb82578ad6b8984d3da95efbfd47"}

experimental_model

Two groups immersing contralateral body sides in stirred water at 10 degrees C

exposure

Two 3-minute head-out immersions at 10 degrees C, with six further immersions of the opposite side between them

limitations

A crossed-side design that separates central from peripheral habituation. Skin temperature profiles were identical between groups, which is what makes the conclusion interpretable.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

Practising on one side of the body calms the response on the other, so the adaptation is in the brain, not the skin.

primary_references

[cold-p9763650] Habituation of the initial responses to cold water immersion in humans: a central or peripheral mechanism? (1998). https://pubmed.ncbi.nlm.nih.gov/9763650/ DOI: 10.1111/j.1469-7793.1998.621be.x

tissue_or_cell_type

Whole body

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 156–167

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two groups immersing contralateral body sides in stirred water at 10 degrees C · source_derived_draft · unverified_draft

### cold-habituation-central Repeated immersions of one body side reduced heart rate and respiratory frequency and volume responses, and reduced the responses evoked on the opposite, previously unhabituated side, despite identical skin temperature profiles, placing the habituation mechanism more centrally than the peripheral receptors. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Practising on one side of the body calms the response on the other, so the adaptation is in the brain, not the skin. organism: Human tissue_or_cell_type: Whole body experimental_model: Two groups immersing contralateral body sides in stirred water at 10 degrees C limitations: A crossed-side design that separates central from peripheral habituation. Skin temperature profiles were identical between groups, which is what makes the conclusion interpretable. exposure: Two 3-minute head-out immersions at 10 degrees C, with six further immersions of the opposite side between them evidence_span: {"source_cache": "artifacts/cold-research/9763650.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0f007b123776a775f6672afa5075a3085c9ddb82578ad6b8984d3da95efbfd47", "start_char": 0, "end_char": 1204, "text_sha256": "0f007b123776a775f6672afa5075a3085c9ddb82578ad6b8984d3da95efbfd47"} [cold-p9763650] Habituation of the initial responses to cold water immersion in humans: a central or peripheral mechanism? (1998). https://pubmed.ncbi.nlm.nih.gov/9763650/ DOI: 10.1111/j.1469-7793.1998.621be.x

evidence_span

{"source_cache": "artifacts/cold-research/10825419.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "df5b07f571e51ae21572ac56aa97d1a9dffcd44fe8f5ead4c929086cbbd37e62", "start_char": 0, "end_char": 2308, "text_sha256": "df5b07f571e51ae21572ac56aa97d1a9dffcd44fe8f5ead4c929086cbbd37e62"}

experimental_model

Cold-adapted winter swimmers and controls during one hour of immersion at 13 degrees C

exposure

One hour of cold water immersion at 13 degrees C

limitations

A comparison of adapted and unadapted people. The adrenaline contribution to thermogenesis is the authors’ estimate from their thermoregulation data, not a direct measurement of a hormone-driven heat fraction.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Human

plain_language

Adapted swimmers hold heat in as well as making more of it, without getting fatter.

primary_references

[cold-p10825419] Thermoregulation in winter swimmers and physiological significance of human catecholamine thermogenesis. (2000). https://pubmed.ncbi.nlm.nih.gov/10825419/ DOI: 10.1111/j.1469-445x.2000.01909.x

tissue_or_cell_type

Whole body thermoregulation

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 650–661

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cold-adapted winter swimmers and controls during one hour of immersion at 13 degrees C · source_derived_draft · unverified_draft

### cold-winter-swimmer-insulation Winter swimmers showed bradycardia and a greater reduction in plasma volume during cooling, indirectly indicating restriction of heat loss, with only a non-significant increase in subcutaneous fat, and exhibited metabolic, hypothermic and insulative types of cold adaptation together. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Adapted swimmers hold heat in as well as making more of it, without getting fatter. organism: Human tissue_or_cell_type: Whole body thermoregulation experimental_model: Cold-adapted winter swimmers and controls during one hour of immersion at 13 degrees C limitations: A comparison of adapted and unadapted people. The adrenaline contribution to thermogenesis is the authors’ estimate from their thermoregulation data, not a direct measurement of a hormone-driven heat fraction. exposure: One hour of cold water immersion at 13 degrees C evidence_span: {"source_cache": "artifacts/cold-research/10825419.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "df5b07f571e51ae21572ac56aa97d1a9dffcd44fe8f5ead4c929086cbbd37e62", "start_char": 0, "end_char": 2308, "text_sha256": "df5b07f571e51ae21572ac56aa97d1a9dffcd44fe8f5ead4c929086cbbd37e62"} [cold-p10825419] Thermoregulation in winter swimmers and physiological significance of human catecholamine thermogenesis. (2000). https://pubmed.ncbi.nlm.nih.gov/10825419/ DOI: 10.1111/j.1469-445x.2000.01909.x

availability_state

biomarker_context Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/20807439.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c", "start_char": 0, "end_char": 1709, "text_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c"}

experimental_model

Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment

exposure

Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h

limitations

The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

After a cardiac arrest the same drug triggers dangerous slowing of the heart at a third of the dose, and atropine stops it.

primary_references

[dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

tissue_or_cell_type

Cardiovascular system

trigger_kind

biomarker_context Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 374–385

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment · source_derived_draft · unverified_draft

### dhc-bezold-jarisch-susceptibility At high levels of dihydrocapsaicin infusion above 2.0 mg/kg/h two single episodes of transient bradycardia and hypotension were observed in 33% of healthy rats, consistent with a TRPV1-agonist-induced Bezold-Jarisch reflex, whereas in resuscitated rats multiple episodes were observed in 100% of the rats at a dose of 0.65 mg/kg/h, and this effect could be completely blocked in the resuscitated rats by pre-treatment with the muscarinic acetylcholine antagonist atropine. Condition category: biomarker_context nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: After a cardiac arrest the same drug triggers dangerous slowing of the heart at a third of the dose, and atropine stops it. organism: Rat tissue_or_cell_type: Cardiovascular system experimental_model: Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment limitations: The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal. exposure: Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/20807439.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c", "start_char": 0, "end_char": 1709, "text_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c"} [dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion

exposure

Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm

limitations

The two control arms are what make this the strongest record here: the knockout shows the receptor is required, and the heat-support arm shows the temperature drop rather than receptor activation is what protects.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Mouse

plain_language

The cooling happens through the receptor, and in these mice it barely touched the circulation.

primary_references

[dhc-p24305062] Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion. (2014). https://pubmed.ncbi.nlm.nih.gov/24305062/ DOI: 10.1152/ajpregu.00329.2013

tissue_or_cell_type

Brain and cardiovascular system

trigger_kind

machinery_impairment Imported condition classification; unverified.

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 296–307

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion · source_derived_draft · unverified_draft

### dhc-hypothermia-requires-trpv1 Dihydrocapsaicin at 1.25 mg/kg produced a stable drop in core temperature to 33 degrees in naive and ischaemia-reperfusion mice but not in TRPV1 knockout mice, and had no measurable effect on heart rate or cerebral perfusion while producing a slight transient drop in mean arterial pressure of less than 6 millimetres of mercury. Condition category: machinery_impairment nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The cooling happens through the receptor, and in these mice it barely touched the circulation. organism: Mouse tissue_or_cell_type: Brain and cardiovascular system experimental_model: Focal cerebral ischaemia-reperfusion in conscious wild-type and TRPV1 knockout mice with osmotic-pump infusion limitations: The two control arms are what make this the strongest record here: the knockout shows the receptor is required, and the heat-support arm shows the temperature drop rather than receptor activation is what protects. exposure: Dihydrocapsaicin 1.25 mg/kg subcutaneously, begun 90 minutes after the start of reperfusion, with normothermia by external heat support as a control arm evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24305062.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17", "start_char": 0, "end_char": 1711, "text_sha256": "6f48560ff0df2e92e757c483dad96056155b0b629ddf0b5d5b41416201adfe17"} [dhc-p24305062] Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion. (2014). https://pubmed.ncbi.nlm.nih.gov/24305062/ DOI: 10.1152/ajpregu.00329.2013

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/20807439.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c", "start_char": 0, "end_char": 1709, "text_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c"}

experimental_model

Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment

exposure

Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h

limitations

The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

The first thing it does is push blood pressure and heart rate up, before anything else happens.

primary_references

[dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

tissue_or_cell_type

Cardiovascular system

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 387–398

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment · source_derived_draft · unverified_draft

### dhc-initial-pressor-response Compared to baseline, infusion of dihydrocapsaicin caused an initial increase in mean arterial blood pressure of 25% in healthy rats and 10% in resuscitated rats, and an initial tachycardic response of 30% and 20% respectively. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: The first thing it does is push blood pressure and heart rate up, before anything else happens. organism: Rat tissue_or_cell_type: Cardiovascular system experimental_model: Continuous intravenous infusion in healthy rats and in rats resuscitated from cardiac arrest, with atropine pre-treatment limitations: The most important safety record in this collection, and the one whose population is the same population the therapy is aimed at. It is a rat study and the episodes are described rather than counted per animal. exposure: Dihydrocapsaicin by continuous intravenous infusion at doses up to and beyond 2.0 mg/kg/h evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/20807439.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c", "start_char": 0, "end_char": 1709, "text_sha256": "49bfe9de2b31cccc9afa70d322f9c96256968e48fdc033102fdb46394e617b0c"} [dhc-p20807439] Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin. (2010). https://pubmed.ncbi.nlm.nih.gov/20807439/ DOI: 10.1186/1471-2261-10-39

evidence_span

{"source_cache": "artifacts/dihydrocapsaicin-research/29590555.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a", "start_char": 0, "end_char": 1882, "text_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a"}

experimental_model

Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy

exposure

Intravenous dihydrocapsaicin, against resiniferatoxin nanoinjected into the nucleus tractus solitarius, with capsazepine and bilateral cervical or subdiaphragmatic vagotomy

limitations

The vagotomy control separates a central vagal route from whatever systemic dihydrocapsaicin uses. Anaesthetised animals, so the cardiovascular numbers are not directly comparable with the conscious studies here.

nutrient_topic

Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin

organism

Rat

plain_language

It turns down the body’s own heater, which is part of why the temperature falls.

primary_references

[dhc-p29590555] Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate. (2018). https://pubmed.ncbi.nlm.nih.gov/29590555/ DOI: 10.1152/ajpregu.00049.2018

tissue_or_cell_type

Nucleus tractus solitarius and brown adipose tissue

Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 400–411

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy · source_derived_draft · unverified_draft

### dhc-shuts-down-brown-fat Intravenous injection of the TRPV1 agonist dihydrocapsaicin decreased brown adipose tissue sympathetic nerve activity, brown adipose tissue temperature, expired carbon dioxide and heart rate, though not mean arterial pressure, during skin cooling in anaesthetised rats. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: It turns down the body’s own heater, which is part of why the temperature falls. organism: Rat tissue_or_cell_type: Nucleus tractus solitarius and brown adipose tissue experimental_model: Urethane-chloralose-anaesthetised rats with nucleus tractus solitarius nanoinjection, sympathetic nerve recording and vagotomy limitations: The vagotomy control separates a central vagal route from whatever systemic dihydrocapsaicin uses. Anaesthetised animals, so the cardiovascular numbers are not directly comparable with the conscious studies here. exposure: Intravenous dihydrocapsaicin, against resiniferatoxin nanoinjected into the nucleus tractus solitarius, with capsazepine and bilateral cervical or subdiaphragmatic vagotomy evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/29590555.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a", "start_char": 0, "end_char": 1882, "text_sha256": "947ba9408e8bbaecee08ba0b2018014faa1d26d3c1fdf8df063e92911e53e19a"} [dhc-p29590555] Activation of TRPV1 in nucleus tractus solitarius reduces brown adipose tissue thermogenesis, arterial pressure, and heart rate. (2018). https://pubmed.ncbi.nlm.nih.gov/29590555/ DOI: 10.1152/ajpregu.00049.2018