Dose-finding, experimental medicine evaluation of sodium valproate for the prevention of post-cardiac surgery myocardial injury

Sodium valproate 15mg/kg/day for ≤14 days before cardiac surgery shows the highest complete treatment adherence (70%) with no severe drug-related adverse effects in adults.

• Why it matters: Post-surgery myocardial injury remains a key risk, and the trial addresses whether sodium valproate can be safely dosed preoperatively and whether myocardial mechanisms explain any benefit.
• What they did: Adults undergoing cardiac surgery were randomized 1:1:1:1 to control or sodium valproate (15mg/kg/day for 1–2 weeks, 4–6 weeks, or 25mg/kg/day for 4–6 weeks); adherence/toxicity were primary, and troponin plus myocardial biopsies were analyzed with snATACseq, snRNAseq, and immunofluorescence.
• The result: In an as-treated analysis, ≤14 days dosing (n=11) showed a trend toward lower post-surgery troponin release alongside pAKT-GSK3β activation, p53 acetylation (K382), and GPX4 ferroptosis protection; p53 silencing attenuated valproate’s ferroptosis protection in vitro.

AI summary of the abstract · may contain errors · not medical advice · read the paper.