Passive hind‐limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury
Bibliographic record
Abstract
Key points Using a wide array of experimental approaches, we demonstrate for the first time that spinal cord injury is associated with a rapid and sustained impairment in cardiac structure and function that is present as early as 1 week post‐injury. We provide novel data demonstrating that spinal cord injury elicits an altered Starling curve and myocardial fibrosis. The latter of these may be secondary to an up‐regulation of transforming growth factor beta‐1 and mothers against decapentaplegic homolog 3 mRNA, both of which form part of a well‐known fibrotic signalling pathway. Passive hind‐limb cycling averts the spinal cord injury‐induced impairments in cardiac structure and function, prevents myocardial fibrosis and improves blood lipid profiles. Passive lower‐limb cycling represents an elegant, cost‐effective and widely accessible therapeutic strategy that may reduce the clinical cardiovascular burden imposed by spinal cord injury and other neurological disorders. Abstract Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio‐metabolic responses to SCI and to establish whether passive hind‐limb cycling elicits a cardio‐protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind‐limb cycling (SCI‐EX; 2 × 30 min day −1 , 5 days week −1 for 4 weeks beginning 6 days post‐SCI). On day 32, cardio‐metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats ( n = 6 SCI and n = 6 SCI‐EX) underwent in vivo echocardiography and basal haemodynamic assessments pre‐SCI and at days 7, 14 and 32 post‐SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up‐regulation of transforming growth factor beta‐1 (TGFβ 1 ) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI‐EX, the initial reduction in left ventricular dimensions and function at day 7 post‐SCI was completely reversed by day 32 post‐SCI, and there were no differences in myocardial contractility between SCI‐EX and CON. Collagen deposition was similar between SCI‐EX and CON. TGFβ 1 and Smad3 were down‐regulated in SCI‐EX. Blood lipid profiles were improved in SCI‐EX versus SCI. We provide compelling novel evidence that passive hind‐limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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) | 0.000 | 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 teacher head, 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".