The mechanism of the positive inotropic action of ketamine on isolated atria of the rat.

1 The effect of ketamine (10-7 M-5 X10-4 M) on electrical and mechanical properties of isolated atria of the rat was investigated. 2. On spontaneously beating right atria, ketamine produced a dose-dependent positive inotropic effect which was accompanied by a progressive reduction in atrial rate. 3 In electrically driven left atria, ketamine produced a dose-dependent positive inotropic effect which was accompanied by a parallel increase in df/dtmax and by a prolongation in the time to peak tension and in the time for total concentration. The positive inotropic effect occurred concomitantly with an increase in the height and duration of the plateau phase of the action potential of atrial fibres. 4 The positive inotropic effect of ketamine varied with the concentration of Ca and Na in the bathing media and the rate of stimulation. 5 Ketamine decreased post-extrasystolic potentiation and the amplitude-interval relationship. 6 The positive inotropic effect of ketamine was inhibited by verapamil (10-6 M) and by caffeine (4 X10-3 M). 7 Ketamine, 5 X10-5M and 10-4M, increased 45Ca uptake in electrically driven left atria. At 10-4M and 5 X10-4M, ketamine also increased 45Ca efflux. 8 These results suggest that ketamine produces its positive inotropic effect by two possible mechanisms. One of these is presumed to be an effect on the cell membrane with leads to an increased Ca influx into atrial fibres; the other is probably related to the inhibition of Ca sequestration by the sarcoplasmic reticulum.