SummaryTo determine the effect of the xanthine oxidase (XO) inhibitor allopurinol on myocardial energy metabolism in a chronic heart failure rat model after myocardial infarct.An AMI model was established in 6-week-old rats via the ligation of the anterior descending coronary artery. Thirty-five rats were randomly divided into the following 3 groups: an ALLO group, an AMI group, and a Sham group. Heart failure was successfully diagnosed via echocardiography and blood tests. Xanthine oxidase (XO), malondialdehyde (MDA), PGC-1α, CPT-1, and GLUT4 were monitored in the myocardium.The TEM results demonstrated that myofilament lysis and mitochondrial swelling were alleviated in the ALLO group compared with the AMI group (without ALLO). The results also demonstrated that cardiac function was significantly improved in the ALLO group compared with the AMI group. Compared with the AMI group, the ALLO group exhibited increased respiratory-chain enzyme activity, as well as increased PGC-1α and CPT-1 mRNA and protein expression, decreased MDA content, and decreased XO and GLUT4 mRNA and protein expression.ALLO improves myocardial energy metabolism in rats with chronic heart failure, which may result from the regulation of PGC-1α in the setting of glycolipid metabolism, enhancing the production of ATP. (Int Heart J 2016; 57: 753-759) Key words: Reactive oxygen species (ROS), Mitochondria C hronic heart failure (CHF) is the terminal stage of heart disease and is the leading cause of death in affected patients. 1-4) The incidence of CHF in adults is nearly 1~2% in developed countries and is above 10% among patients older than 70 years of age.5) Synthetic treatments and assist devices have been introduced to improve myocardial remodeling, strengthen myocardial contraction, and alleviate cardiac overload.
6,7)Editorial p.661 Improving cardiomyocyte energy metabolism has attracted attention as a potential therapy for CHF. As early as 1934, Decherd, et al 8) observed that cardiomyocytes exist in a state of "energy starvation" in the setting of CHF. Recent studies have demonstrated that the activity of respiratory-chain enzymes decreases and changes in glycolipid metabolism in the setting of CHF, resulting in decreased myocardial ATP production. Additionally, the levels of reactive oxygen species (ROS) increase rapidly following myocardial infarction. An important source of reactive oxygen species ROS, 9,10) xanthine oxidase (XO), is over-expressed in CHF, 11,12) causes mitochondrial injury, and inhibits the activity of various respiratory-chain enzymes.13) Additionally, increased evidence indicates that cardiomyocyte glycolipid metabolism is disrupted in CHF. 14,15) Opie, et al 16) observed increased concentrations of high-energy phosphate among patients with CHF following the intravenous administration of ALLO, an XO inhibitor. However, the mechanisms underlying the activity of ALLO in the setting of CHF remain poorly understood. In this study, rat models of CHF introduced via the ligation of coronary arteries were constructe...
