CONTRIBUTION OF GLYCOGEN AND EXOGENOUS GLUCOSE TO GLUCOSE-METABOLISM DURING ISCHEMIA IN THE HYPERTROPHIED RAT-HEART

Although hypertrophied hearts have increased rates of glycolysis under aerobic conditions, it is controversial as to whether glucose metabol ism during ischemia is altered in the hypertrophied heart. Because end ogenous glycogen stores are a key source of glucose during ischemia, w e developed a protocol to label the glycogen pool in hearts with eithe r [H-3]glucose or [C-14]glucose, allowing for direct measurement of bo th glycogen and exogenous glucose metabolism during ischemia. Cardiac hypertrophy was produced in rats by banding the abdominal aorta for an 8-week period. Isolated hearts from aortic-banded and sham-operated r ats were initially perfused under substrate-free conditions to decreas e glycogen content to 40% of the initial pool size. Resynthesis and ra diolabeling of the glycogen pool with [H-3]glucose or [C-14]glucose we re accomplished in working hearts by perfusion for a 60-minute period with 11 mmol/L [H-3]glucose or [C-14]glucose, 0.5 mmol/L lactate, 1.2 mmol/L palmitate, and 100 mu mol/mL insulin. Although glycolytic rates during the: aerobic perfusion were significantly greater in hypertrop hied hearts compared with control hearts, glycolytic rates from exogen ous glucose were not different during low-How ischemia. The contributi on of glucose from glycogen was also not different in hypertrophied he arts compared with control hearts during ischemia (1314+/-665 versus 7 76+/-310 nmol.min(-1).g dry wt(-1), respectively). Glucose oxidation r ates decreased during ischemia but were not different between the two groups. However, in both hypertrophied and central hearts, the ratio o f glucose oxidation to glycolysis was greater for glucose originating from glycogen than from exogenous glucose. Our data demonstrate that g lycogen is a significant source of glucose during low-flow ischemia, b ut the data do not differ between hypertrophied and control hearts.