The effects of ketamine on conduction velocity and maximum rate of rise of action potential upstroke in guinea pig papillary muscles: comparison with quinidine.
Using standard microelectrode techniques, the effects of ketamine on the maximum rate of rise of action potential upstroke (Vmax) and the conduction velocity were examined and compared with the effects of quinidine, a sodium channel blocker, in isolated guinea pig papillary muscles. Both ketamine and quinidine decreased Vmax and the square of the conduction velocity in a concentration-dependent manner. The conduction slowing paralleled the decreases in Vmax, suggesting that the sodium current inhibition produced by these drugs is responsible for the conduction slowing. In the presence of quinidine, a train of stimulation after a quiescent period produced an exponential decline in Vmax, and the decrease in Vmax was enhanced by increasing stimulation frequency (i.e., use-dependent block). Ketamine significantly depressed Vmax of the first action potential after a long quiescent period (tonic block), and failed to produce a further decrease in Vmax during the subsequent train of stimulation. The decrease in Vmax was enhanced by simultaneous administration of ketamine and quinidine. Thus, ketamine decreases conduction velocity by inhibiting the sodium current. The mode of action on cardiac conduction is similar to that of quinidine, but different from that of volatile anesthetics which produce conduction slowing by impairing cell-to-cell coupling. However, ketamine produces a tonic block of the sodium channel while quinidine produces a use-dependent block. We conclude that ketamine should be administered with caution to patients receiving Class I antiarrhythmic drugs.
Hara
Y
Y
Department of Pharmacology, School of Medicine, Chiba University, Japan.
Tamagawa
M
M
Nakaya
H
H
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects* / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009431:Neural Conduction; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011802:Quinidine / Q000494:pharmacology*
D007649:Ketamine; D011802:Quinidine