We tested the hypothesis that improved
ischemia tolerance in an isolated working rat heart preparation can be achieved by interventions other than ischemic preconditioning. Hearts were perfused at near-physiological workload with
bicarbonate buffer containing
glucose (10 mM). A preischemic period of 25 min was followed by 15 min of global
ischemia and 30 min of reperfusion under preischemic conditions. Hearts came from either fed or fasted animals (groups 1 and 2). In group 3
lactate (10 mM) and
insulin (10 mU/ml) were added to the perfusate of fasted animals. In group 4 hearts from fed animals were perfused with
glucose (10 mM) and were ischemically preconditioned by one cycle of
ischemia between 10 and 15 min of the preischemic perfusion. Cardiac power and
glucose uptake were measured continuously to assess functional and metabolic recovery. In addition, we measured the time to return of aortic flow.
Glucose metabolites and the ratio of latent of free
citrate synthase activity (
citrate synthase ratio, a marker for the structural integrity of mitochondria) were determined at selected time points. Groups 2, 3, and 4 recovered significantly faster than group 1, whereas recovery of power showed an improvement in groups 3 and 4 only. In addition, there was an early increase in
glucose uptake during reperfusion in these two groups, suggesting an early need for
glucose substrate.
Glycogen levels decreased with
ischemia in all groups and returned to preischemic levels in groups 2, 3, and 4. The
citrate synthase ratio was low in the control group and preserved in the groups showing improved functional recovery. We conclude that metabolic interventions may be as effective as ischemic preconditioning in protecting the heart from ischemic injury.