The in vivo study of cardiac mechano-electric and mechano-mechanical coupling during heart development in zebrafish
Bibliographic record
Abstract
In the adult heart, acute adaptation of electrical and mechanical activity to changes in mechanical load occurs via feedback processes known as “mechano-electric coupling” and “mechano-mechanical coupling.” Whether this occurs during cardiac development is ill-defined, as acutely altering the heart’s mechanical load while measuring functional responses in traditional experimental models is difficult, as embryogenesis occurs in utero, making the heart inaccessible. These limitations can be overcome with zebrafish, as larvae develop in a dish and are nearly transparent, allowing for in vivo manipulation and measurement of cardiac structure and function. Here we present a novel approach for the in vivo study of mechano-electric and mechano-mechanical coupling in the developing zebrafish heart. This innovative methodology involves acute in vivo atrial dilation (i.e., increased atrial preload) in larval zebrafish by injection of a controlled volume into the venous circulation immediately upstream of the heart, combined with optical measurement of the acute electrical (change in heart rate) and mechanical (change in stroke area) response. In proof-of-concept experiments, we applied our new method to 48 h post-fertilisation zebrafish, which revealed differences between the electrical and mechanical response to atrial dilation. In response to an acute increase in atrial preload there is a large increase in atrial stroke area but no change in heart rate, demonstrating that in contrast to the fully developed heart, during early cardiac development mechano-mechanical coupling alone drives the adaptive increase in atrial output. Overall, in this methodological paper we present our new experimental approach for the study of mechano-electric and mechano-mechanical coupling during cardiac development and demonstrate its potential for understanding the essential adaptation of heart function to acute changes in mechanical load.
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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) | 0.001 | 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".