Thomas W Johnson, James Holt, Anna Kleyman, Shengyu Zhou, Eva Sammut, Vito Domenico Bruno, Charlotte Gaupp, Giacomo Stanzani, John Martin, Pietro Arina, Julia Deutsch, Raimondo Ascione, Mervyn Singer, Alex Dyson
Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion...
April 25, 2024: Redox Biology