Transient Negative Dromotropic Effects of Catecholamines on Canine Purkinje Fibers Exposed to Halothane and Isoflurane

The time-dependent effects of catecholamines in combination with volatile anesthetics on conduction velocity of canine Purkinje fibers were investigated to evaluate a controversial older hypothesis that the arrhythmogenic interaction between epinephrine and halothane may involve abnormal conduction. Two groups of 12 in vitro preparations were stimulated at 150 beats/min. In the first group, 5 μM epinephrine by itself did not alter conduction velocity over a 10-min period from a control mean value of 1.97 ± 0.08 m/s. However, 5 μM epinephrine, in the presence of either 0.4 mM halothane or 0.4 mh4 isoflurane, reduced conduction velocity (P ≤0.01) by about 10--15% within 3--5 min, with recovery toward control by 10 min. The mean conduction velocity at the 4th minute of exposure, in the presence of halothane and epinephrine (1.65 ± 0.11 m/s), was lower (P ≤ 0.01) than that obtained in the presence of isoflurane and epinephrine (1.74 ± 0.07 m/s). In the second group, both 5 μM norepinephrine and 5 μM epinephrine, in the presence of either anesthetic, depressed conduction velocity (P ≤ 0.01) with a similar time course. The reduction of conduction velocity with norepinephrine was less (P ≤ 0.01) than that with epinephrine, and again the decreases of conduction velocity were larger (P ≤ 0.01) with 0.4 mM halothane than 0.4 mM isoflurane. The negative dromotropic interaction between epinephrine and halothane was not associated with reduction of the action potential amplitude or rate of phase 0 depolarization, which suggests that the catecholamine effect may involve modulation of passive membrane properties, such as cell-to-cell coupling, rather than changes of the peak inward current during the action potential upstroke. These results confirm an earlier report that epinephrine potentiates the modest slowing of conduction produced by halothane in Purkinje fibers and indicate that catecholamines' abnormally slow conduction with halothane is greater than with the “less sensitizing” anesthetic isoflurane.