DILTIAZEM INHIBITS THE LATE INCREASE IN EXTRACELLULAR POTASSIUM BY MAINTAINING GLYCOLYTIC ATP SYNTHESIS DURING MYOCARDIAL-ISCHEMIA

During myocardial ischemia, the extracellular potassium concentration increases in a triphasic pattern, an initial early increase, a constan t phase, and a late increasing phase. The aim of this study was to det ermine whether diltiazem inhibits the late increasing phase by maintai ning glycolytic adenosine triphosphate (ATP) synthesis in ischemic myo cardium. The extracellular potassium concentration and pH were measure d simultaneously with ion-sensitive electrodes during 30 min of global ischemia in isolated guinea-pig hearts. In the control hearts, the la te increasing phase occurred 13 min after the onset of ischemia when t he change in extracellular pH had reached a plateau. There was a sharp increase in the myocardial lactate level in the control hearts, which was maintained for similar to 8 min after the onset of ischemia. Iodo acetate (1 mM) led to a ATP depletion and rapid accumulation in extrac ellular potassium shortly after the onset of ischemia without a decrea se in extracellular pH. The preischemic treatment with diltiazem (3 mu M) reduced cardiac function both before ischemia and during the early period of ischemia. Diltiazem almost completely abolished the late in creasing phase with a continuous decrease in extracellular pH througho ut the ischemic period. The myocardial lactate level in the diltiazem- treated group increased sharply between 2 and 15 min after the onset o f ischemia. The myocardial ATP level was preserved throughout the isch emic period. This study shows that diltiazem inhibits the late increas ing phase in extracellular potassium by maintaining glycolytic ATP syn thesis during ischemia.