The positive inotropic action of sodium fluoroacetate on guinea-pig ventricular myocardium.

Abstract

1. In the isolated papillary muscle of the guinea pig sodium fluoroacetate (FAc) produced, after an initial decrease in force of concentration, a transient positive inotropic effect which was due to an increase in the rate of force development. Time to peak force was shortened and relaxation time was prolonged whereas total contraction time was barely affected. Threshold and maximally effective concentrations for the positive inotropic effect were 1×10−5 and 5×10−3 M, respec tively. 2. Noradrenaline depletion by pretreatment of the animals with reserpine or β-adrenoceptor blockade with 5×10−6 M (±)-propranolol did not prevent the positive inotropic effect of 1×10−3 M FAc. 3. Reduction of [Na]0 from 140 to 70 mM (sucrose for osmotic adjustment) resulted in a decrease of the positive inotropic effect of 1×10−3 M FAc to about 54% of control, whereas a diminution of [K]0 from 9.6 to 2 mM caused a 4-fold increase. 4. The positive inotropic effect of 1×10−3 M FAc progressively increased when the stimulation frequency was increased from 0.064 to 0.5 Hz; rested-state contractions (0.004 Hz) were not increased by FAc. At a stimulation frequency of 2 Hz, FAc developed exclusively a negative inotropic effect which resulted in a contracture. 5. In the presence of ceveratrum alkaloids (0.8 μM veratridine or 30 nM germitrine), the positive inotropic effect of 1×10−3 M FAc was markedly augmented (about 5-fold). Tetrodotoxin (10 μM) prevented the enhancing effect of 0.8 μM veratridine on the positive inotropic effect of FAc. 6. At a low stimulation frequency (0.064 Hz), 1×10−3 M FAc prolonged the action potential duration of a guinea-pig papillary muscle within 2 h by 30%. At a stimulation rate of 1 Hz, a shortening of the action potential duration by 35% and a depolarization of the membrane resting potential by 4.3 mV occurred. 7. It is tentatively concluded that FAc like cardioactive steroids exerts its positive inotropic effect by an interference with the Na-extrusion mechanism thereby facilitating the Ca-uptake by an Na−Ca exchange.