Acta Pharm. 67 (2017) 293-307
Original research paper
excitability and conduction alterations caused by
levobupivacaine in rat
SEÇKİN TUNCER, TÜLAY TUNCER PEKER, İLKSEN BURAT, ERHAN KIZILTAN, BARKIN İLHAN and NİZAMETTİN DALKILIÇ
1 N.E. University, Meram Faculty of Medicine, Biophysics Department, Konya, Turkey
2 Ankara University, Faculty of Medicine, Anesthesiology Department, Ankara, Turkey
3 Başkent University, Faculty of Medicine, Physiology Department, Ankara, Turkey
Accepted May 10, 2017
Published online June 14, 2017
In this study, effects of the long-acting amide-type local anesthetic levobupivacaine on axonal conduction and excitability parameters of the rat sciatic nerve were thoroughly examined both in vitro and in vivo. In order to deduce its effects on isolated nerve conduction, compound nerve action potential (CNAP) recordings were performed using the suction method over sciatic nerves of Wistar rats before and after administration of 0.05 % (1.7 mmol L1) levobupivacaine. Levobupivacaine caused complete CNAP area and amplitude depression by blocking conduction in a time-dependent manner.
To assess the influence of levobupivacaine on in vivo excitability properties, threshold-tracking (TT) protocols were performed at sciatic nerves of rats injected with perineural 0.05 % (1.7 mmol L1) levobupivacaine or vehicle alone. Charge-duration TT results revealed that levobupivacaine increases the rheobase and decreases the strength-duration time constant, suggesting interference of the anesthetic with the opening of Na+ channels. Twenty and 40 % threshold electrotonus curves were found for both groups to follow the same paths, suggesting no significant effect of levobupivacaine on K+ channels for either the fastest or relatively slow conducting fibers. Current-threshold relationship results revealed no significant effect on axonal rectifying channels. However, according to the results of the recovery cycle protocol yielding the pattern of excitability changes following the impulse, potential deviation was found in the recovery characteristics of Na+ channels from the absolute refractory period. Consequently, conduction blockage caused by levobupivacaine may not be due to the passive (capacitive) properties of axon or the conductance of potassium channels but to the decrease in sodium channel conductance.
Keywords: levobupivacaine, nerve conduction, excitability, threshold electrotonus