Mitochondria-mediated cardioprotection by trimetazidine in rabbit heart failure

► TMZ preserves cardiac function in the conditions of non-ischemic rabbit HF. ► The beneficial effect of TMZ was not linked to fatty acid oxidation inhibition. ► Cardioprotection by TMZ was mediated by prevention of Ca2 +-induced mPTP opening. ► The mechanism relies on re-coupling of the mitochondrial respiratory chain and mtNOS. ► Mild inhibition of the mitochondrial complex II by TMZ was beneficial in HF.