Metabolic disorders due to changes in cytosolic
glucose utilisation are suspected to be involved in the increased sensitivity of the aged myocardium to
ischemia. This study presents the first direct measurement of
glucose utilisation in hearts from senescent rats during low-flow
ischemia under different conditions of substrate delivery and
glycogen stores. Isolated hearts from young adult (4-months-old) and senescent (24-months-old) rats were subjected to 30 min coronary flow restriction (residual flow rate=2% of control flows). Experiments were performed using
glucose-free or
glucose-enriched (11 mmol/L) perfusion media. The effects of increased
glycogen stores were assessed after 24-h fasting in both age groups.
Ischemic contracture was measured via a left-ventricular balloon. Ageing increased
ischemic contracture under both conditions of substrate delivery in fed rat hearts. The increase in ischemic tolerance induced by fasting in senescent rat hearts was less than that seen in young rat hearts. Moreover, fasting decreased
glucose utilisation in hearts from young rats, an effect which was not found in hearts from old rats. Furthermore, myocardial
glycogen utilisation was increased in all groups of aged rats compared with that of young adults, particularly under fasting conditions. It is concluded that fasting is less detrimental to the aged myocardium during low-flow
ischemia than to the young myocardium because it does not further reduce exogenous
glucose utilisation, and it stimulates
glycogen consumption. Moreover, a reduction in exogenous
glucose utilisation, which is only partly compensated for by increased glycogenolytic flux could be, at least in part, responsible for the increased
ischemic contracture in hearts from old fed rats. Finally, our
glucose-free experiments suggest that residual oxidative phosphorylation during low-flow
ischemia might be less relevant in hearts from senescent rats than in those from young adults.