METHODS: Methods and results: Cardiac hypertrophy was induced in vivo by CIH for up to 10 weeks. Autophagy was assessed by measuring changes in Beclin-1, LC3 cleavage, and ultrastructural autophagosomes. We also measured changes in the activation of AMP-activated protein kinase, a critical myocardial autophagy regulator. The results approximately indicates a sharply retreatment of autophagy after a compensate increasing. We further identify the autophagy impairment by autophagy flux assay with chloroquine or not. Cardiomyopathy in response to impaired autophagy was assessed by measuring serum atrial natriuretic peptide levels, heart/body weight ratios, cardiomyocyte size, fibrotic area, cardiomyocyte apoptosis, and the hemodynamic index. Rapamycin (an inducer of autophagy) can attenuated cardiomyopathy by restoring autophagy. 3-Methyladenine (an autophagy inhibitor) exerted the opposite effect. We compared AMPK activation under normoxia or CIH and detected AMPK inactivation during CIH. Then we dual-regulated AMPK activation and found a same changing trend of autophagy and AMPK activation in vivo. These results indicate that AMPK is a direct target under CIH which can induce autophagy impairment. Morphological and abundant changes in autophagosomes and changes in the expression of beclin1 and LC3 cleavage couple with the unchanging of Cathepsin D and p62 accumulation suggested that CIH mainly interfered with the initial step of autophagy which induces more cellular construct damage. Moreover, CIH induced impaired autophagy which decreased cell viability and ATP supply and increased cardiomyocyte apoptosis, indicating that impaired autophagy reduced cardiomyocyte survival. Rescue experiment with rapamycin will ameliorate these pathological changes while 3-MA will deteriorate them. Moreover, the similar function of AMPK further definite the autophagy regulating role of AMPK under CIH.