The Mechanism of the Positive Inotropic Action of Ketamine on Isolated Atria of the Rat

Abstract

1 The effect of ketamine (10-7 M-5 x 10-4 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/dtm,, and by a prolongation in the time to peak tension and in the time for total contraction. 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 (4x 103 M).7 Ketamine, 5 x 10-5 M and 10-4 M, increased 45Ca uptake in electrically driven left atria. At 10-4 M and 5 x 10-4 M, 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 which leads to an increased Ca influx into atrial fibres; the other is probably related to the inhibition of Ca sequestration by the sarcoplasmic reticulum.

Tonic Block of the Sodium and Calcium Currents by Ketamine in Isolated Guinea Pig Ventricular Myocytes.

“…The tight-seal, whole cell voltage clamp technique was used. After the gigaohmseal between the tip of the electrode and the cell membrane was established, the membrane patch was disrupted by Ketamine affects the contractile tension and the action potential configuration in isolated mammalian myocardial preparations [1,2,24]. It has been demonstrated that ketamine inhibits several potassium currents and L-type calcium current (I Ca ) in isolated single cardiomyocytes of guinea pigs and rats [6].…”

The effect of oxytocin on contractile responses and 45Ca movements in rat isolated aortic strips

“…After 7 min, both control and experimental preparations were washed in 50 mM La3+-Ca-free solution for 5 min in order to remove extracellular bound calcium. Then the strips were removed and the radioactivity of the samples counted in a liquid scintillation counter as previously described (Barrig6n et al, 1982;. To determine 45Ca efflux, aortic strips were incubated in 45Ca-labelled Tris solution (specific activity 2 ptCi ml-') for 2 h. Tissues were then rinsed in non-radioactive Tris solution before being placed in successive tubes containing 2 ml of Ca-free Tris solution every minute for the duration ofthe washout (25 min).…”

Effects of Intravenous Anesthetics on Function and Metabolism in the Reperfused Working Rat Heart

“…Rusy et al (25) showed that ketamine inhibition of transsarcolemmal Ca2+ influx played a major role in the negative inotropic action and that ketamine had relatively little effect on the availability of Ca 2+ stored in and released from the sarcoplasmic reticulum. On the other hand, it is also suggested that ketamine produces positive inotropic effects by increasing Ca 2+ influx (23). Recently, Endou et al (26) have reported that these diverse effects could be explained by the consistent suppression of the transsarcolemmal ionic currents of ketamine and by the species and tissue differences in membrane ionic current systems.…”

“…The cardiovascular action of these agents remains controversial (18)(19)(20)(21)(22)(23). Ketamine produces sympathomimetic pressor effects mediated via an intact autonomic nervous system (11).…”