Mechanism of the inhibitory action of NaF and Na-fluoroacetate on the cardiac function and the carbohydrate metabolism of the isolated bullfrog's heart.

Abstract

The effects of inhibition of the aerobic glycolysis by sodium fluoride and inhibition of respiration by sodium fluoroacetate on the carbohydrate metabolism and cardiac function were investigated on the isolated bullfrog's heart perfused with the heparinized blood.0.005 M. fluoride did not show any inhibitory effect but an inotropic effect. 0.01-0.02 M. fluoride induced the inhibition of aerobic glycolysis, i. e., the definite elevation of the blood pyruvate level at the end of 2 hours perfusion, the increase of oxygen consumption and the decrease of glucose uptake, and simultaneously the decrease of cardiac output due to the restriction of diastolic relaxation. The same mechanism is suggested on the inhibition of glycolysis and the restriction of diastolic relaxation as Mg-fluoro-phosphate formation inside the cell, while the inotropic effect in the lower concentration may be due to the effect of calcium fixation on the cell membrane in the form of calcium fluoride as Loewi expected.0.001-0.01 M. fluoroacetate diminished significantly the oxygen consumption with the elevation of blood lactate and pyruvate level at the end of 2 hours perfusion and the augmentation of glucose uptake, while no diminution of the cardiac output. However, when the initial oxygen consumption is close to the level of the warm blooded animal by elevation of the environmental temperature and the heart rate, the cardiac output falls down simultaneously with the depression of the oxygen consumption. It is concluded that the glycolysis is sufficient enough for supplying the energy for the ordinary cardiac function but not enough for the excessive energy demand.