ADENOSINE RECEPTOR BLOCKADE ENHANCES GLYCOLYSIS IN HYPOPERFUSED GUINEA-PIG MYOCARDIUM

Objective: This study tested the hypothesis that endogenous adenosine depresses anaerobic glycolysis in preischaemic and moderately ischaemi c myocardium. Methods: Isolated, working guinea-pig hearts, perfused w ith glucose-fortified Krebs-Henseleit buffer, were subjected to 15 min mild hypoperfusion (coronary flow 60% of baseline) followed by 10 min ischaemia (coronary flow 20% of baseline). Adenosine A, receptors wer e blocked with 8-p-sulfophenyl theophylline (8-SPT; 20 mu M). Glucose oxidation and lactate production from exogenous glucose were assessed from (CO2)-C-14 and [C-14]lactate formation, respectively, from [U-C-1 4]glucose. Energy metabolites, glycolytic intermediates and glycogen w ere measured in extracts of stop-frozen preischaemic, mildly hypoperfu sed and ischaemic myocardium. Results: Adenosine receptor blockade did not affect left ventricular function assessed from heart rate X press ure product and pressure X volume work although coronary flow was slig htly reduced. Adenosine receptor blockade increased glucose uptake (P <0.05) by 100% during preischaemia and by 74% during mild hypoperfusio n, and increased lactate production from exogenous glucose (P <0.05) b y 89% during preischaemia and fourfold during mild hypoperfusion, but did not stimulate glucose oxidation under any condition. Glycogen degr adation was not increased by adenosine receptor blockade during ischae mia. Crossover plots of glycolytic intermediates revealed that phospho fructokinase was activated by adenosine receptor blockade at all three levels of perfusion. Conclusion: Endogenous adenosine attenuates anae robic glycolysis in normally perfused, hypoperfused and ischaemic myoc ardium by blunting phosphofructokinase activity; this effect is mediat ed by adenosine A(1) receptors.