Impaired myosin isoform shift and calcium transients contribute to cellular pathogenesis of rat cirrhotic cardiomyopathy
Bibliographic record
Abstract
Abstract Background & Aims Cirrhotic cardiomyopathy is a recently recognized entity, but detailed cellular and molecular mechanisms remain unclarified. We aimed to elucidate the role of myosin heavy chain isoform shifts and their relation to calcium transients in the contractile kinetics of cirrhotic rats. Methods Cirrhosis was induced in male Lewis Brown‐Norway rats by bile duct ligation (BDL). Myosin heavy chain (MHC) isoform distribution was evaluated by gel electrophoresis. Contractile force, Ca 2+ transients and cell shortening were studied at varied frequency and extracellular [Ca 2+ ]. T‐tubular integrity was analysed by power spectrum analysis of images of myocytes stained with di‐8‐ANEPPS. Results Compared with sham controls, the phenotypes of cirrhotic rats were as follows: (a) alpha‐myosin heavy chain shifted to beta‐MHC isoform; (b) mild loss of T‐tubular integrity in myocytes; (c) a reduced maximum and rate of rise of the Ca 2+ transient (max F / F o ); (d) a reduction in both the rate of rise and fall of contraction; (e) decreased maximal force‐generating capacity; (f) loss of the inotropic effect of increased stimulus frequency; (g) unchanged sensitivity of force development to varied extracellular [Ca 2+ ] and (h) increased spontaneous diastolic sarcomere length fluctuations. Conclusion Cardiomyocytes and ventricular trabeculae in a cirrhotic rat model showed features of typical heart failure including systolic and diastolic prolongation, impaired force‐frequency relation and decreased force‐generating capacity. Impaired myosin isoform shift and calcium transients are important contributory mechanisms underlying the pathogenesis of the heart failure phenotype seen in cirrhosis.
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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 | 0.000 | 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 | 0.000 |
| 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".