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

Area of Science:

• Cardiology
• Metabolic Research
• Ischemia-Reperfusion Injury

Background:

• Endogenous substrate availability significantly influences cardiac metabolism.
• Nutritional status impacts myocardial response to ischemic events.
• Understanding glucose utilization is crucial for managing heart conditions.

Purpose of the Study:

• To investigate the effect of endogenous substrate levels on glucose utilization in rat hearts following ischemia.
• To compare glucose uptake in fed versus fasted hearts post-ischemia.
• To determine if 2-[18F]fluoro-2-deoxy-D-glucose (2-FDG) accurately reflects glucose utilization under varying nutritional states and ischemic conditions.

Main Methods:

• Isolated working rat hearts from fed and 16-hour fasted animals were perfused with glucose and 2-FDG.
• Mechanical performance and 2-FDG uptake were measured during and after 15 minutes of global ischemia.
• Glucose and lactate metabolic rates were calculated.

Main Results:

• Fasting increased cardiac glycogen and triglyceride content.
• Post-ischemic 2-FDG uptake was significantly depressed in fed hearts but unchanged in fasted hearts.
• Fasted hearts demonstrated higher post-ischemic glucose utilization compared to fed hearts.
• Lactate utilization increased in fed hearts during reperfusion, coinciding with suppressed glucose utilization.

Conclusions:

• 2-FDG is a reliable tracer for glucose utilization, irrespective of nutritional state or ischemia.
• Myocardial glucose utilization post-ischemia is highly dependent on the animal's pre-ischemic nutritional status.
• Lactate from glycolysis can inhibit exogenous glucose uptake during early reperfusion without impacting mechanical recovery.