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 t he maximum rate of rise of action potential upstroke (V-max) and the c onduction velocity were examined and compared with the effects of quin idine, a sodium channel blocker, in isolated guinea pig papillary musc les. Both ketamine and quinidine decreased V-max and the square of the conduction velocity in a concentration-dependent manner. The conducti on slowing paralleled the decreases in V-max, suggesting that the sodi um current inhibition produced by these drugs is responsible for the c onduction slowing. In the presence of quinidine, a train of stimulatio n after a quiescent period produced an exponential decline in V-max an d the decrease in V-max was enhanced by increasing stimulation frequen cy (i.e., use-dependent block). Ketamine significantly depressed V-max of the first action potential after a long quiescent period (tonic bl ock), and failed to produce a further decrease in V-max during the sub sequent train of stimulation. The decrease in V-max was enhanced by si multaneous administration of ketamine and quinidine. Thus, ketamine de creases 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 s lowing by impairing cell-to-cell coupling. However, ketamine produces a tonic block of the sodium channel while quinidine produces a use-dep endent block. We conclude that ketamine should be administered with ca ution to patients receiving Class I antiarrhythmic drugs.