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Carbon Dioxide as a Novel Blood Pressure Therapy for Neurogenic Orthostatic Hypotension

2024· article· en· W4398165863 on OpenAlexaffabout
Jacquie Baker, Shaun Ranada, Anthony V. Incognito, Robert S. Sheldon, Richard J. A. Wilson, Aaron A. Phillips, Satish R. Raj

Bibliographic record

VenuePhysiology · 2024
Typearticle
Languageen
FieldMedicine
TopicCardiovascular Syncope and Autonomic Disorders
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsOrthostatic vital signsCarbon dioxideBlood pressureMedicineAnesthesiaIntensive care medicineInternal medicineChemistry

Abstract

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BACKGROUND: On standing, people with neurogenic orthostatic hypotension (nOH) experience plummeting blood pressure (>20/10mmHg), crippling symptoms, and syncope. Current blood pressure therapies lack effcacy and have serious side effects. In healthy people, increased inspired CO 2 increases blood pressure. This raises the tantalizing possibility that increased inspired CO 2 may effectively treat nOH patients. OBJECTIVE: We aimed to understand if increased inspired CO 2 can increase standing blood pressure in nOH. METHODS: Seventeen patients with nOH (F=5; 71±8 years) completed three randomized sit-to-stand tests with inspired CO 2 maintained 0mmHg (0CO 2 ), +5mmHg (+5CO 2 ) or +10mmHg (+10CO 2 ) relative to baseline. Respiratory and hemodynamics (blood pressure, heart rate, stroke volume, cardiac output, systemic vascular resistance) were continuously measured. Data are reported as mean ± SD. The change (stand-sit) in respiratory and hemodynamics between 0mmHg, +5mmHg and +10mmHg were compared using a repeated measures ANOVA with a Bonferroni correction. RESULTS: Inspired CO 2 caused a dose-dependent increase in standing blood pressure (0CO 2 :-43±25mmHg; +5CO 2 :-22±26mmHg; +10CO 2 :-4±30mmHg; p<0.001). Blood pressure changes were predominantly facilitated by increased stroke volume (0CO 2 :-10±10mL; +5CO 2 :-5±10mL; +10CO 2 :0.1±10mL;p<0.001) and cardiac output (0CO 2 :-0.2±0.6L/min; +5CO 2 :0.2±0.5L/min; +10CO 2 :0.7±0.5L/min; p<0.001) as neither the changes in heart rate (p=0.2) nor systemic vascular resistance (p=0.6) were different across CO 2 conditions. Breathing CO 2 decreased the percentage of time that standing systolic blood pressure dropped ≥20mmHg (0CO 2 :75±35%; +5CO 2 :48±38%; +10CO 2 :32±37%; p<0.001) and fewer patients met the blood pressure criteria for orthostatic hypotension (p=0.02). CONCLUSION: Our data indicates increased inspired CO 2 can increase standing blood pressure in nOH patients by increasing stroke volume and cardiac output. CO 2 may offer a novel pressor therapy for patients with nOH. This work was supported by a University of Calgary Seed Funding (S.R.R). J.R.B is supported by a Canadian Institutes of Health Research (CIHR) Fellowship, a Libin Cardiovascular Institute Post-Doctoral Fellowship in Women’s Cardiovascular Health, the Natural Sciences and Engineering Research Council of Canada (NSERC) Brain CREATE Program, and a Canadian Cardiovascular Society Fellowship. S.I.R. is supported by the NSERC Brain CREATE Program, an Alberta Graduate Excellence Scholarship, and an Alberta Strategy for Patient Oriented SUPPORT Unit scholarship. A.V.I is supported by a CIHR Fellowship and an Achievers in Medical Science Postdoctoral Fellowship. 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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.814
Threshold uncertainty score0.448

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.014
GPT teacher head0.260
Teacher spread0.246 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2024
Admission routes2
Has abstractyes

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