Nonstereospecific actions of ketamine isomers on the force of contraction, spontaneous beating rate, and Ca2+ current in the guinea pig heart.
Ketamine possesses stereospecific actions of anesthesia with the S(+)-isomer being three to four times as potent an anesthetic as the R(-)-isomer. We investigated the mechanical and electrophysiologic effects of ketamine isomers in guinea pig cardiac preparations. Both isomers decreased the contractile force of electrically driven papillary muscles and the spontaneously beating rate of the right atria in a concentration-dependent manner. There were no significant differences between the S(+)- and R(-)-isomers for these measured variables. Consistent with the results from mechanical experiments, electrophysiologic experiments using whole cell voltage clamp techniques revealed that both isomers suppressed identically the transsarcolemmal Ca2+ current (ICa), which plays a role in the generation of the force of contraction and the spontaneous firing of sinoatrial node cells. In conclusion, the optical 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 present results could be extrapolated to the clinical setting.
Sekino
N
N
Department of Anesthesiology, Yokohama City University School of Medicine, Japan.
Endou
M
M
Hajiri
E
E
Okumura
F
F
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D000778:Anesthetics, Dissociative; D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine