NONSTEREOSPECIFIC ACTIONS OF KETAMINE ISOMERS ON THE FORCE OF CONTRACTION, SPONTANEOUS BEATING RATE, AND CA2-PIG HEART( CURRENT IN THE GUINEA)

Ketamine possesses stereospecific actions of anesthesia with the S(+)- isomer being three to four times as potent an anesthetic as the R(-)-i somer. We investigated the mechanical and electrophysiologic effects o f ketamine isomers in guinea pig cardiac preparations. Both isomers de creased the contractile force of electrically driven papillary muscles and the spontaneously beating rate of the right atria in a concentrat ion-dependent manner. There were no significant differences between th e S(+)- and R(-)-isomers for these measured variables. Consistent with the results from mechanical experiments, electrophysiologic experimen ts using whole cell voltage clamp techniques revealed that both isomer s suppressed identically the transsarcolemmal Ca2+ current (I-Ca), whi ch plays a role in the generation of the force of contraction and the spontaneous firing of sinoatrial node cells. In conclusion, the optica l isomers of ketamine have equipotent cardiodepressant effects in the guinea pig. Inasmuch as the S(+)-isomer is the more potent anesthetic, it could offer significant clinical advantage over the R(-)-isomer or the racemate, in terms of impairment of cardiac functions, if the pre sent results could be extrapolated to the clinical setting.