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Background Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular (LV) remodeling and heart failure (HF).Recombinant human neuregulin-1 (rhNRG-1)improves cardiac function in models of experimental HF and in clinical trials; however,its impact on mitochondrial function during chronic HF remains largely unknown.The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction.Methods Sixty adult rats underwent sham or coronary ligation to induce HF.Four weeks after ligation,29 animals with LV ejective fraction ＜50％ were randomized to receive either vehicle or rhNRG-1 (10 μg·kg-1·d-1,I.V.) for 10 days,another 12 sham-operated animals were given no treatment.Echocardiography was used to determine physiological changes.Mitochondrial membrane potential (MMP),respiratory function and tissue adenosine triphosphate (ATP) production were analyzed.Cytochrome c expression and cardiomyocyte apoptosis were determined.Oxidative stress was evaluated by reactive oxygen species production using fluorescence assays and gene expression of glutathione peroxidase measured by real-time quantitative PCR.Results Compared with sham-operated animals,vehicle treated HF rats exhibited severe LV remodeling and dysfunction,significant mitochondrial dysfunction,increased mitochondrial cytochrome c release,increased myocyte apoptosis and enhanced oxidative stress.Short-term treatment with rhNRG-1 significantly attenuated LV remodeling and cardiac function.Concomitant with this change,mitochondrial dysfunction was significantly attenuated; with ATP production,MMP and respiratory function restored,cytochrome c release and apoptosis inhibited,and oxidative stress reduced.Conclusion The present study demonstrated that rhNRG-1 can significantly improve LV remodeling and cardiac function in the failing heart,this beneficial effect is related to reducing mitochondrial dysfunction,myocyte apoptosis and oxidative stress.