To discriminate between the electrophysiologic and arrhythmogenic effects of
lidocaine and those of
bupivacaine, isolated, perfused canine hearts were exposed to toxic concentrations of the drugs. The preparations included the sinus node and right atrium, and, in some cases, the AV node and interventricular septum as well. Action potentials were recorded from these areas, and right atrial twitch amplitude and spontaneous rate and rhythm were monitored. Heart rate was depressed in a dose-dependent manner by both drugs, as was atrial twitch amplitude. In the absence of arrhythmias, the spontaneous rate decreased less than 30% with
lidocaine up to 50 micrograms/ml, and with
bupivacaine up to 5 micrograms/ml. The twitch depression reflected a potency ratio for
bupivacaine (mol. wt. 288) to
lidocaine (mol. wt. 234) on a mass basis of 8.1:1. The most prominent
arrhythmia found was
sinoatrial block, which was caused by both drugs with a potency ratio for
bupivacaine to
lidocaine of 15.4:1 and was reversed by 0.02 microgram/ml
norepinephrine.
Sinus arrhythmias, block of retrograde conduction from AV node to atrium, and irregular rhythms originating within the AV node were observed with both drugs at concentrations similar to those which produced
sinoatrial block. The atrial action potential revealed decreased upstroke velocity, overshoot, and height with both
lidocaine and
bupivacaine, with potency ratios (
bupivacaine:
lidocaine) ranging from 15:1 to 26:1. In septal cells, both drugs depressed upstroke velocity, and
bupivacaine lengthened action potentials by up to 14%, but
lidocaine did not. The major difference between
bupivacaine and
lidocaine in this study was the higher potency of the former agent with respect to electrophysiologic end-points.