Effects of ropivacaine on action potential configuration and ion currents in isolated canine ventricular cardiomyocytes.
BACKGROUND
Despite the widespread clinical application of ropivacaine, there is little information on the cellular cardiac effects of the drug. In the current study, therefore, the concentration-dependent effects of ropivacaine on action potential morphology and the underlying ion currents were studied and compared with those of bupivacaine in isolated canine ventricular cardiomyocytes.


METHODS
Action potentials were recorded from the enzymatically dispersed cells using sharp microelectrodes. Conventional patch clamp and action potential voltage clamp arrangements were used to study the effects of ropivacaine on transmembrane ion currents.


RESULTS
Ropivacaine induced concentration- and frequency-dependent changes in action potential configuration, including shortening of the action potentials, reduction of their amplitude and maximum velocity of depolarization, suppression of early repolarization, and depression of plateau. Reduction in maximum velocity of depolarization was characterized with an EC50 value of 81 +/- 7 microm at 1 Hz. Qualitatively similar results were obtained with bupivacaine (EC50 = 47 +/- 3 microm). Under voltage clamp conditions, a variety of ion currents were blocked by ropivacaine: L-type calcium current (EC50 = 263 +/- 67 microm), transient outward current (EC50 = 384 +/- 75 microm), inward rectifier potassium current (EC50 = 372 +/- 35 microm), rapid delayed rectifier potassium current (EC50 = 303 +/- 47 microm), and slow delayed rectifier potassium current (EC50 = 106 +/- 18 microm).


CONCLUSIONS
Ropivacaine, similarly to bupivacaine, can modify cardiac action potentials and the underlying ion currents at concentrations higher than the usual therapeutic range. However, in cases of overdose, cardiac complications may be anticipated both during and after anesthesia due to the blockade of various ion currents.
Szabó
Adrienn
A
Department of Dentistry, University of Debrecen, Debrecen, Hungary.
Szentandrássy
Norbert
N
Birinyi
Péter
P
Horváth
Balázs
B
Szabó
Gergely
G
Bányász
Tamás
T
Márton
Ildikó
I
Magyar
János
J
Nánási
Péter P
PP
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D000077212:Ropivacaine; D016276:Ventricular Function
D000577:Amides; D007473:Ion Channels; D000077212:Ropivacaine