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H₂S-donors are cardioprotective in ischemia/reperfusion (I/R) injury. Some H₂S-donors exert their beneficial effects in a nitric oxide (NO)-dependent manner, while others act using NO-independent pathways. The aims of the present study were to (i) evaluate whether H₂S-donors with distinct pharmacodynamic properties act synergistically in I/R injury and (ii) determine if H₂S-donors remain cardioprotective in obese mice. C57BL/6 mice were subjected to 30 min of ischemia followed by 120 min of reperfusion. Donors were administered intravenously at the end of ischemia (Na₂S: 1 μmol/kg, GYY4137: 25 μmol/kg, AP39: 0,25 μmol/kg), while the 3-mercaptopyruvate sulfurtransferase (10 mg/kg) inhibitor was given intraperitonially 1 h prior to ischemia. Infarct size was estimated by 2,3,5-triphenyltetrazolium staining, while the area at risk was calculated using Evans blue. All three donors reduced infarct size when …