THE CARDIAC EFFECTS OF BUPIVACAINE AND RO PIVACAINE ON CONTRACTILITY AND ACTION-POTENTIALS OF ISOLATED GUINEA-PIG ATRIA - INFLUENCE OF DIFFERENT EXTRACELLULAR POTASSIUM CONCENTRATIONS
H. Wulf et al., THE CARDIAC EFFECTS OF BUPIVACAINE AND RO PIVACAINE ON CONTRACTILITY AND ACTION-POTENTIALS OF ISOLATED GUINEA-PIG ATRIA - INFLUENCE OF DIFFERENT EXTRACELLULAR POTASSIUM CONCENTRATIONS, Anasthesist, 42(8), 1993, pp. 516-520
The cardiotoxicity of long acting local anaesthetics is still a matter
of controversy. Therefore, the effects of bupivacaine and ropivacaine
on cardiac contractility and electrophysiologic parameters were evalu
ated in the presence of different extracellular potassium concentratio
ns. Methods. In strips from left atria of guinea pigs action potential
s were induced to obtain cumulative dose response curves for bupivacai
ne (racemic mixture) and ropivacaine (S-enantiomere). Effects on force
of contraction and parameters of the action potential (especially max
imum upstroke velocity, dV/dt(max), as an indirect measure of fast sod
ium channel function) were compared for low (2.7 mM) and high (8.7 mM)
extracellular K+ concentrations (n = 7-8). Results. At low K+ concent
ration, bupivacaine and ropivacaine depressed force of contraction and
dV/dt(max) in a dose-dependent manner. At higher local anaesthetic co
ncentrations, action potential amplitude decreased and action potentia
l duration was prolonged. There was no influence on the resting membra
ne potential (Tables 2, 3). At high K+ concentration, both local anaes
thetics induced effects similar to those observed with low K+, but the
dose-response curves for contractility and dV/dt(max) were shifted le
ftward. The EC50 of bupivacaine for the negative inotropic effect and,
analogously, for dV/dt(max) was approximately 10 times lower. Similar
results were observed for ropivacaine (Figs. 1, 2). Conclusion. This
study confirms the dependence of the cardiodepressive effects of bupiv
acaine on the extracellular K+ concentration (i.e. membrane potential)
. The present investigation shows a similar dependence for the effects
of ropivacaine, a new long-lasting local anaesthetic. Our results con
cerning the potential dependency of dV/dt(max) depression are compatib
le with the binding of bupivacaine to the inactivated state of the sod
ium channel protein preferentially (modulated receptor hypothesis). Th
us accumulation of block will occur if stimulation frequency is in an
appropriate range. Though we found striking analogies between potentia
l dependency of dV/dt(max) depression and negative inotropic effect, t
here is no firm evidence that the sodium channel block by bupivacaine
or ropivacaine substantially participates in the latter effect. An inf
luence on other ionic channels such as the calcium channel remains to
be evaluated.