Feeding and fasting determine postischemic glucose utilization in isolated working rat hearts

Abstract

To assess the effects of endogenous substrate on glucose utilization after 15 min of ischemia, we perfused isolated working rat hearts from fed and fasted (16 h) animals with glucose and the positron-emitting glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose (2-FDG). Hearts were perfused in a recirculating system with bicarbonate buffer containing glucose (10 mM) and 2-FDG (0.5 microCi/ml). Mechanical performance and 2-FDG uptake were measured on-line, and glucose and lactate metabolic rates were calculated. Fasting raised the glycogen content by 25% and the triglyceride content by 38%. Hearts in both groups recovered preischemic function. Rates of 2-FDG uptake during the preischemic period were the same in both groups. In contrast, during the postischemic period rates of 2-FDG uptake were significantly depressed in hearts of fed animals but were unchanged in hearts of fasted animals. Thus hearts of fasted animals took up more 2-FDG during the postischemic period than hearts of fed animals (P less than 0.005). The lumped constant (range, 0.38-0.40) was the same in both groups before and after ischemia. Glucose utilization was suppressed during the postischemic period in hearts of fed animals, whereas at the same time lactate utilization was significantly increased. We conclude that 1) 2-FDG accurately traces glucose utilization independent of the nutritional state or ischemic insult; 2) reversibly ischemic, viable myocardium exhibits vastly different rates of glucose utilization depending on the nutritional state of the animal before ischemia; 3) lactate derived from glycolysis suppresses utilization of exogenously supplied glucose in the early reperfusion period without affecting postischemic performance.

Glucose for the Heart

“…26 Unlike liver and skeletal muscle, heart muscle increases its glycogen content with fasting. 27 This observation is consistent with the general principle that fatty acids, the predominant fuel for the heart during fasting, inhibit glycolysis more than glucose uptake, thereby rerouting glucose toward glycogen synthesis. Glycogen stores are also increased by insulin, from the simultaneous stimulation of glucose transport and glycogen synthase activity.…”

Quantitative assessment of prolonged metabolic abnormalities in reperfused canine myocardium.

“…Nine adult mongrel dogs weighing [24][25][26][27][28][29][30][31][32][33][34][35] kg (mean, 28.2+3.2 kg) were studied. Animals were anesthetized with sodium thiamylal (Surital) 2 mg/kg i.v.…”

Compartmentation of hexokinase in rat heart. A critical factor for tracer kinetic analysis of myocardial glucose metabolism.

“…The development of a simplified graphical method to determine rates of glucose uptake based on the trapping oftracer in an irreversible compartment (4,5), has allowed studies ofthe kinetics ofglucose uptake by external detection in the intact heart both in vitro and in vivo. Initial work on the rapid kinetic analysis of glucose metabolism in the intact heart has been reported (6)(7)(8) and has suggested that the relationship between uptake of the tracer, 2-[ '8F Ifluoro-2-deoxy-D-glucose, and uptake ofthe tracee, glucose, is not always constant.…”