We investigated the effect of resveratrol, a popular natural polyphenolic 
compound with antioxidant and proautophagic actions, on postinfarction heart 
failure. Myocardial infarction was induced in mice by left coronary artery 
ligation. Four weeks postinfarction, when heart failure was established, the 
surviving mice were started on 2-week treatments with one of the following: 
vehicle, low- or high-dose resveratrol (5 or 50 mg/kg/day, respectively), 
chloroquine (an autophagy inhibitor), or high-dose resveratrol plus chloroquine. 
High-dose resveratrol partially reversed left ventricular dilation (reverse 
remodeling) and significantly improved cardiac function. Autophagy was augmented 
in those hearts, as indicated by up-regulation of myocardial 
microtubule-associated protein-1 light chain 3-II, ATP content, and autophagic 
vacuoles. The activities of AMP-activated protein kinase and silent information 
regulator-1 were enhanced in hearts treated with resveratrol, whereas Akt 
activity and manganese superoxide dismutase expression were unchanged, and the 
activities of mammalian target of rapamycin and p70 S6 kinase were suppressed. 
Chloroquine elicited opposite results, including exacerbation of cardiac 
remodeling associated with a reduction in autophagic activity. When resveratrol 
and chloroquine were administered together, the effects offset one another. In 
vitro, compound C (AMP-activated protein kinase inhibitor) suppressed 
resveratrol-induced autophagy in cardiomyocytes, but did not affect the events 
evoked by chloroquine. In conclusion, resveratrol is a beneficial 
pharmacological tool that augments autophagy to bring about reverse remodeling 
in the postinfarction heart.