ANTECEDENT ISCHEMIA REVERSES EFFECTS OF ADENOSINE ON GLYCOLYSIS AND MECHANICAL FUNCTION OF WORKING HEARTS

This study compared the effects of adenosine (Ado) on the coupling of glycolysis and glucose oxidation and on mechanical function in normal hearts and in hearts subjected to transient ischemia. Isolated wet-kin g rat hearts were perfused with Krebs containing 1.2 mM palmitate and 100 mu U/ml insulin. After 15 min of aerobic perfusion, hearts underwe nt either two cycles of 10 min of ischemia and 5 min of reperfusion (s tressed) or 30 min of aerobic perfusion (control), After 45 min, heart s underwent either aerobic perfusion for 35 min (series A) or 30 min o f ischemia and 30 min of reperfusion (series B), In series A, left ven tricular minute work (LV work) was similar in control and stressed hea rts and was not affected by Ado (500 mu M) or N-6-cyclohexyladenosine (CHA 0.5 mu M). Ado reduced glycolysis by 49% in control hearts but in creased glycolysis by 74% in stressed hearts. CHA inhibited glycolysis in both groups by 50 and 62%, respectively, In series B, LV work duri ng reperfusion recovered to a similar extent in untreated control and stressed hearts. In control hearts, Ado reduced glycolysis by 50% whil e enhancing LV work to 81% of preischemic values. In stressed hearts. Ado increased glycolysis by 34% and depressed LV work to 9%, whereas C HA inhibited glycolysis by 53% and LV work to 91%. These data indicate that coupling of glycolysis to glucose oxidation is a key determinant of mechanical function of the postischemic myocardium. They also show that the metabolic and protective effects of Ado depend on the status of the heart before sustained ischemia.