Carbon Dioxide as a Novel Blood Pressure Therapy for Neurogenic Orthostatic Hypotension
Bibliographic record
Abstract
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 CO2 increases blood pressure. This raises the tantalizing possibility that increased inspired CO2 may effectively treat nOH patients. OBJECTIVE: We aimed to understand if increased inspired CO2 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 CO2 maintained 0mmHg (0CO2), +5mmHg (+5CO2) or +10mmHg (+10CO2) 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 CO2 caused a dose-dependent increase in standing blood pressure (0CO2:-43±25mmHg; +5CO2:-22±26mmHg; +10CO2:-4±30mmHg; p<0.001). Blood pressure changes were predominantly facilitated by increased stroke volume (0CO2:-10±10mL; +5CO2:-5±10mL; +10CO2:0.1±10mL;p<0.001) and cardiac output (0CO2:-0.2±0.6L/min; +5CO2:0.2±0.5L/min; +10CO2:0.7±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 CO2 conditions. Breathing CO2 decreased the percentage of time that standing systolic blood pressure dropped ≥20mmHg (0CO2:75±35%; +5CO2:48±38%; +10CO2:32±37%; p<0.001) and fewer patients met the blood pressure criteria for orthostatic hypotension (p=0.02). CONCLUSION: Our data indicates increased inspired CO2 can increase standing blood pressure in nOH patients by increasing stroke volume and cardiac output. CO2 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 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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".