Effect of alkalosis on glycolysis in the isolated rat heart

Abstract

Isolated rat hearts were perfused with glucose-containing buffer at pH of 7.4, 8.2, or 8.5. High pH perfusions caused a greater than threefold increase in myocardial lactate production and increased exogenous glucose and endogenous glycogen utilization. These effects were found whether alkalosis was produced by lowering the PCO2 [CO2 tension] or by increasing the bicarbonate content of the perfusion medium. When hearts were perfused with glucose-U-14C, 14CO2 production was similar in control and alkalotic experiments. The specific radioactivity of the lactate produced was the same with normal and high pH perfusions, indicating that a similar proportion of glucose utilization to glycogenoly-sis occurred in the 2 conditions. Analysis of myocardial glycolytic intermediate compounds demonstrated declines in glucose 6-phosphate and fructose 6-phosphate, and increases in fructose 1,6-diphosphate and dihydroxyacetone phosphate in alkalosis. Myocardial creatine phosphate increased in alkalosis, but there was no change in adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, or inorganic phosphate. These results indicate that alkalosis causes increased glycolysis by stimulating the phosphofructokinase reaction. This stimulation is not caused by changes in adenosine triphosphate or its breakdown products, but may be related to direct pH effects on the enzyme.