TRANSIENT NEGATIVE DROMOTROPIC EFFECTS OF CATECHOLAMINES ON CANINE PURKINJE-FIBERS EXPOSED TO HALOTHANE AND ISOFLURANE

The time-dependent effects of catecholamines in combination with volat ile anesthetics on conduction velocity of canine Purkinje fibers were investigated to evaluate a controversial older hypothesis that the arr hythmogenic interaction between epinephrine and halothane may involve abnormal conduction. Two groups of 12 in vitro preparations were stimu lated at 150 beats/min. In the first group, 5 muM epinephrine by itsel f did not alter conduction velocity over a 10-min period from a contro l mean value of 1.97 +/- 0.08 m/s. However, 5 muM epinephrine, in the presence of either 0.4 mM halothane or 0.4 mM isoflurane, reduced cond uction velocity (P less-than-or-equal-to 0.01) by about 10-15% within 3-5 min, with recovery toward control by 10 min. The mean conduction v elocity at the 4th minute of exposure, in the presence of halothane an d epinephrine (1.65 +/- 0.11 m/s), was lower (P less-than-or-equal-to 0.01) than that obtained in the presence of isoflurane and epinephrine (1.74 +/- 0.07 m/s). In the second group, both 5 muM norepinephrine a nd 5 muM epinephrine, in the presence of either anesthetic, depressed conduction velocity (P less-than-or-equal-to 0.01) with a similar time course. The reduction of conduction velocity with norepinephrine was less (P less-than-or-equal-to 0.01) than that with epinephrine, and ag ain the decreases of conduction velocity were larger (P less-than-or-e qual-to 0.01) with 0.4 mM halothane than 0.4 mM isoflurane. The negati ve dromotropic interaction between epinephrine and halothane was not a ssociated with reduction of the action potential amplitude or rate of phase 0 depolarization, which suggests that the catecholamine effect m ay involve modulation of passive membrane properties, such as cell-to- cell coupling, rather than changes of the peak inward current during t he 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' abn ormally slow conduction with halothane is greater than with the ''less sensitizing'' anesthetic isoflurane.