Acute severe hypoxia induces prolonged cardiac transcriptomic remodeling despite rapid functional recovery

Electrocardiography and transcriptomic profiling were combined to quantify the short- and long-term effects of acute, severe hypoxia on adult zebrafish hearts. We hypothesized that rapid recovery of cardiac electrical activity does not necessarily indicate concurrent recovery at the molecular level. Continuous ECG recordings revealed pronounced bradycardia during hypoxic exposure, characterized by reduced heart rate and prolonged RR intervals. Upon reoxygenation, heart rate increased and RR intervals shortened within 2–5 min as oxygen levels normalized, MS-222 (tricaine) anesthesia was discontinued, and β-adrenergic stimulation (isoproterenol) restored cardiac excitability. Despite this swift physiological recovery, transcriptomic analyses conducted seven days post-hypoxic exposure demonstrated persistent differential gene expression in previously hypoxia-affected fish compared with normoxic shams. Upregulated genes were associated with stress response and tissue remodeling, whereas downregulated genes reflected cell-cycle regulation and metabolic adjustment. Together, these findings indicate a subtle transcriptional landscape consistent with cellular stabilization rather than ongoing injury. In summary, while ECG data alone might imply that acute hypoxic effects are transient, transcriptomic evidence reveals a sustained molecular imprint of hypoxic stress in the zebrafish heart that persists well beyond apparent functional recovery.