Glucose uptake and glycogen levels are increased in pig heart after repetitive ischemia

Abstract

Repetitive myocardial ischemia increases glucose uptake, but the effect on glycogen is unclear. Thirteen swine instrumented with a hydraulic occluder on the circumflex (Cx) artery underwent 10-min occlusions twice per day for 4 days. After 24 h postfinal ischemia and in the fasted state, echocardiogram and positron emission tomography imaging for blood flow ([13N]-ammonia) and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake were obtained. Tissue was then collected for ATP, creatine phosphate (CP), glycogen, and glucose transporter-4 content, and hexokinase activity. After reperfusion, regional function and CP-to-ATP ratios in the Cx and remote regions were similar. Despite the absence of stunning, the Cx region demonstrated higher glycogen levels (33 ± 11 vs. 24 ± 11 μmol/g; P < 0.05), and this increase correlated well with the increase in FDG uptake ( r 2 = 0.78; P < 0.01). Hexokinase activity was also increased relative to remote regions (0.62 ± 0.29 vs. 0.37 ± 0.19 IU/g; P < 0.05), with no difference in GLUT-4 content. In summary, 24 h after repetitive ischemia, glucose uptake and glycogen levels are increased at a time that functional and bioenergetic markers of stunning have recovered. The significant correlation between glycogen content and FDG accumulation in the postischemic region suggests that increased rates of glucose transport and/or phosphorylation are linked to increased glycogen levels in hearts subjected to repetitive bouts of ischemia.