INHIBITION OF GLYCOGENOLYSIS BY A GLUCOSE ANALOG IN THE WORKING RAT-HEART

The effects of BAY o 1245, an inhibitor of alpha-amylo-1, 6-glucosidas e, on glycogenolysis and post-ischemic functional recovery were invest igated in isolated perfused rat hearts. Working rat hearts were perfus ed during 30 min with 11 mM glucose (controls) and, in some hearts, wi th 1 mu M insulin or 5 mM lactate to increase their glycogen concentra tion. The hearts were then submitted to 10 min of no-flow ischemia and reperfused during 15 min with 11 mM glucose alone. Glycogen content w as increased by 50% in hearts perfused with insulin or lactate, During ischemia, glycogen breakdown was similar in the control and lactate g roups, but was abolished in the insulin-group, At reperfusion, functio nal recovery was improved in glycogen-loaded hearts compared to contro ls, When hearts were perfused with 1 mM BAY o 1245, added before ische mia, glycogenolysis was inhibited in the three groups and functional r ecovery was hampered in both the control and lactate groups. In the in sulin group, however, the functional recovery was barely affected by B AY o 1248. We conclude that: (i) BAY o 1248 is an inhibitor of heart g lycogen breakdown; (ii) the consequences of inhibition of ischemic gly cogenolysis on post-ischemic functional recovery depend on the conditi ons; and (iii) the protective effect of insulin does not result from i schemic glycogenolysis. (C) 1997 Academic Press Limited.