Acute Intermittent Hypoxia Improves Orthostatic Tolerance in Chronic but not Acute Spinal Cord Injured Rats
Bibliographic record
Abstract
Spinal cord injury (SCI) causes hypotension and orthostatic intolerance due to disrupted sympathetic input to the heart and vasculature following injury 1 . A neuro‐therapeutic strategy shown to increase somatic motor function below the injury is acute intermittent hypoxia (AIH). While AIH is known to improve control over respiratory and non‐respiratory motor systems with incomplete cervical SCI 2,3 , cardio‐autonomic responses to AIH after SCI are unknown. In able‐bodied individuals, AIH increases blood pressure (BP), improves orthostatic tolerance (OT), and heightens sympathetic activity 4 . In incomplete SCI, intact neural pathways regulating sympathetic nerve activity suggest the potential for AIH to increase sub‐lesional sympathetic activity, thus improving cardiovascular function. Previous work has demonstrated that the response to AIH is greatest in rats at least 4 weeks post‐injury due to reestablishment of serotonergic pathways 2 , therefore the purpose of this project is to investigate whether AIH improves OT in rats following acute (2 weeks) and/or chronic (4 weeks) high‐thoracic SCI. We believe AIH will improve OT more in chronically versus acutely injured rats. 12 Wistar rats underwent T3 300 kdyn SCI. At 14 (n=6) or 28 (n=6) days post‐SCI rats were tracheotomized, ventilated and arterial catheterization was performed to assess BP. Rats were subjected to lower body negative pressure (LBNP; recorded with manometer) to decrease mean arterial pressure (MAP) by 5 and 10 mmHg for 1 min. Rats were exposed to isocapnic AIH (10 x 1‐min F I O 2 =0.10 separated by 2 min of F I O 2 =1.00; targeting a PaCO 2 of 40 mmHg). LBNP was repeated 90 minutes post‐AIH, the expected peak response. Blood gases were measured pre‐ and post‐AIH. A mixed‐design ANOVA was performed to examine effects of time post‐SCI (group) and AIH (treatment) on change in box pressure required to decrease MAP by ‐5 and ‐10 mmHg. There was a significant group*treatment interaction for the ‐5 mmHg (p=0.011) and ‐10 mmHg LBNP stage (p=0.017). Post hoc comparisons demonstrate that in chronic SCI the box pressure required to drop MAP by ‐5 and ‐10mmHg was increased by 41±16% (p=0.009) and 46±22% (p=0.079) versus pre‐AIH, respectively, implying improved OT (Fig 1). We demonstrate that AIH has the capacity to improve OT in a rodent model of SCI in a chronic, but not acute setting. References 1. DeVeau et al. Autonomic Neuroscience (2018) 2. Golder & Mitchell Journal of Neuroscience (2005) 3. Prosser‐Loose et al. Journal of Neurotrauma (2015) 4. Stuckless et al. Journal of Physiology (2020)
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".