Sodium thiosulfate treatments results in increased serum free thiol levels and improved cardiac function post ST-elevated myocardial infarction
K Ricken, I A Ertugrul, M S L Y de Koning, A R Bourgonje, P van der Harst, H van Goor, E LipsicAbstract
Background
– Myocardial ischemia–reperfusion injury causes heart damage through oxidative stress and inflammation, and effective drug therapies are still lacking. Sodium thiosulfate (STS) is a strong antioxidant with anti-inflammatory and vasodilatory effects, partly through reducing reactive oxygen species and releasing hydrogen sulfide. STS may also help preserve circulating free thiols, which reflect the body’s redox balance and are associated with cardiovascular outcomes.
Purpose
– This study evaluates whether administration of STS increases free thiols (FTs), as a marker of systemic oxidative stress, and studies the associations of FT with outcomes after ST-segment elevation myocardial infarction (STEMI).
Methods
– FTs were detected in archived plasma samples from 298 participants of a neutral randomized trial on STS after STEMI. FT levels were determined at presentation with STEMI and at 9 hours after reperfusion. Outcomes included infarct size and left ventricular ejection fraction (LVEF), both determined with cardiac magnetic resonance imaging at 4 months follow-up.
Results
– A total of 256 patients were included (placebo n=131, STS n=125; mean age 62±11.7 years, 23% female). Baseline characteristics were comparable between groups, except for ethnicity. Serum free thiols were higher in the STS group at baseline and remained significantly higher after 9 hours of treatment; the increase from baseline to 9 hours was significantly greater with STS (all p<0.001). Higher free thiol levels at 9 hours were independently associated with higher LVEF in univariable analysis and after adjustment for age, sex, STS treatment, angiographic variables, and cardiac biomarkers (β 0.048 per µmol/L increase, p<0.001). Free thiols at 9 hours were not associated with infarct size at 4 months.
Conclusions
- STS treatment significantly increased circulating free thiol levels, reflecting an improved systemic redox balance. Elevated free thiols were independently associated with better left ventricular function on cardiac MRI 4-months post-STEMI, although no association with infarct size was observed. These findings support a role for STS-mediated redox modulation in functional recovery after myocardial ischemia–reperfusion injury.