Thiol-based cardioprotection

Acute myocardial infarction (MI) constitutes a major health problem worldwide. Over the last decades, the prognosis after MI has improved. Nevertheless, rates of death and occurrence of heart failure after MI remain substantial. It is hypothesized that reperfusion of ischemic myocardium paradoxically induces myocardial injury and experimental data suggest that this injury can contribute up to 50% of the final myocardial infarct size. Effective treatments targeting this so called ‘ischemia-reperfusion (I/R) injury’ in humans which may potentially limit infarct size and improve prognosis are currently lacking.

In this thesis several compounds that might provide a therapy to target I/R injury were explored. In Part I, associations of ketone bodies and free thiols with outcomes after MI were investigated. In case that associations with outcomes are observed, this might suggest that these compounds might provide a future therapy for I/R injury. In part II of this thesis, a first attempt in humans was performed to translate the wealth of preclinical data demonstrating that hydrogen sulfide (H2S)-donating compounds provide infarct-sparing effects. In the GIPS-IV randomized clinical trial it was investigated whether sodium thiosulfate, a strong antioxidant and H2S-donating compound, reduces infarct size in 380 patients with a first myocardial infarction.