AJP - Heart and Circulatory Physiology, Vol 244, Issue 1 80-H88, Copyright © 1983 by American Physiological Society
Differential effect of verapamil isomers on sinus node and AV junctional region
H. O. Gloor and F. Urthaler
The l- and d-isomers of verapamil were selectively perfused into the sinus
node artery and atrioventricular (AV) node artery of 48 dogs. Injection of
l-verapamil into the sinus node artery during sinus rhythm and into the AV
node artery during AV junctional rhythm depresses both sinus rhythm and AV
junctional rhythm significantly more than does the d-isomer. l-Verapamil is
three to four times more powerful than d-verapamil. Injection of the
isomers into the AV node artery during sinus rhythm rapidly impairs AV
conduction. Increments in conduction time are measured exclusively at the
level of the A-H interval of the His bundle electrogram, and l-verapamil is
six times more powerful than d-verapamil. Neither d- nor l-verapamil in
concentrations that exert a profound negative chronotropic effect or cause
AV block, has any significant effect on transatrial or His bundle
conduction. Thus these concentrations of d-verapamil have little or no
significant effect on the fast sodium channel, but both verapamil isomers
affect the slow channel. The main difference in action between l- and
d-verapamil appears to be only quantitative in nature. The sinus node is
significantly more sensitive to the negative chronotropic action of
verapamil than is the AV junctional pacemaker, and this differential
responsiveness appears to be related to the different intrinsic rates of
the two pacemakers. During sinus rhythm (either in the presence or absence
of atropine) sinus node automaticity is less affected than AV conduction
when verapamil is given parenterally. We propose that this greater negative
dromotropic effect of verapamil is also in part due to a rate-dependent
process, since during sinus rhythm AV junctional cells have to be
depolarized at frequencies significantly higher than their intrinsic rates.
