FASTING, LACTATE, AND INSULIN IMPROVE ISCHEMIA TOLERANCE IN RAT-HEART- A COMPARISON WITH ISCHEMIC PRECONDITIONING

We tested the hypothesis that improved ischemia tolerance in an isolat ed working rat heart preparation can be achieved by interventions othe r than ischemic preconditioning. Hearts were perfused at near-physiolo gical workload with bicarbonate buffer containing glucose (10 mM). A p reischemic period of 25 min was followed by 15 min of global ischemia and 30 min of reperfusion under preischemic conditions. Hearts came fr om 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 an imals. In group 4 hearts from fed animals were perfused with glucose ( 10 mM) and were ischemically preconditioned by one cycle of ischemia b etween 10 and 15 min of the preischemic perfusion. Cardiac power and g lucose uptake were measured continuously to assess functional and meta bolic recovery. In addition, we measured the time to return of aortic flow. Glucose metabolites and the ratio of latent to free citrate synt hase activity (citrate synthase ratio, a marker for the structural int egrity of mitochondria) were determined at selected time points. Croup s 2, 3, and 4 recovered significantly faster than group 1, whereas rec overy of power showed an improvement in groups 3 and 4 only. In additi on, there was an early increase in glucose uptake during reperfusion i n these two groups, suggesting an early need for glucose substrate. Gl ycogen levels decreased with ischemia in all groups and returned to pr eischemic 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.