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 working rat hearts were perfused with Krebs containing 1.2 mM palmitate and 100 microU/ml insulin. After 15 min of aerobic perfusion, hearts underwent either two cycles of 10 min of ischemia and 5 min of reperfusion (stressed) or 30 min of aerobic perfusion (control). After 45 min, hearts underwent either aerobic perfusion for 35 min (series A) or 30 min of ischemia and 30 min of reperfusion (series B). In series A, left ventricular minute work (LV work) was similar in control and stressed hearts and was not affected by Ado (500 microM) or N6-cyclohexyladenosine (CHA 0.5 microM). Ado reduced glycolysis by 49% in control hearts but increased glycolysis by 74% in stressed hearts. CHA inhibited glycolysis in both groups by 50 and 62%, respectively. In series B, LV work during reperfusion recovered to a similar extent in untreated control and stressed hearts. In control hearts, Ado reduced glycolysis by 50% while enhancing LV work to 81% of preischemic values. In stressed hearts, Ado increased glycolysis by 34% and depressed LV work to 9%, whereas CHA 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.
Finegan
B A
BA
Department of Anaesthesia, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Gandhi
M
M
Lopaschuk
G D
GD
Clanachan
A S
AS
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
D002317:Cardiovascular Agents; C027513:N(6)-cyclohexyladenosine; D006003:Glycogen; D000241:Adenosine