Stereoselective effects of the enantiomers of bupivacaine on the electrophysiological properties of the guinea‐pig papillary muscle

Abstract

1 Direct myocardial effects of the S(-)-and R(+)-enantiomers of bupivacaine were compared in the guinea-pig isolated papillary muscle by recording transmembrane action potentials with the standard microelectrode technique. 2 In 5.4 mm K+, at a stimulation rate of 1 Hz, the maximal rate of depolarization ( was reduced to 59.9 + 1.4% (n = 10) of control (mean+ s.e.mean) in the presence of 10puM R(+)-bupivacaine, and to 76.7 + 1.2% (n = 14) in the presence of the same concentration of S(-)-bupivacaine. This was mainly due to a difference in time constant at which block dissipated during the diastolic period. Recovery was slower in the presence of R(+)-bupivacaine. The slower recovery in the presence of R(+)-bupivacaine resulted also in a more pronounced frequency-dependent block of f,,,X.3 Time constants for recovery from use-dependent block became significantly faster for both enantiomers on hyperpolarization, while no significant change was observed at depolarization. At all membrane potentials recovery was slower in the presence of R( + )-bupivacaine. 4 The action potential duration (APD) was shortened to a greater extent in the presence of R(+)-bupivacaine over a large range of stimulation frequencies.5 We conclude that S(-)-bupivacaine affects VP"X and APD in the guinea-pig papillary muscle less than the R( + )-enantiomer at different rates of stimulation and resting membrane potentials.

Comparison of 0.75% levobupivacaine with 0.75% racemic bupivacaine for peribulbar anaesthesia

“…Laboratory animal and isolated heart preparations have demonstrated reduced cardiotoxicity of the S-isomer. It has a lower affinity for the cardiac sodium channels and dissociates more quickly, thereby reducing the potential for development of re-entrant arrhythmias particularly ventricular fibrillation [9,14,15]. Gristwood et al demonstrated the reduced toxicity of levobupivacaine compared to the proprietary racemate in a double-blind, crossover study [16].…”

The efficacy and safety of 0.75% levobupivacaine vs 0.75% bupivacaine for peribulbar anaesthesia

“…Further animal studies comparing the isomers of bupivacaine indicate a higher affinity and, therefore, a greater inhibition of the n-max with dextrobupivacaine than with levobupivacaine. 20 The dextro-enantiomer's greater affinity for myocardial potassium channels is even more marked, 21 and this may also be partially responsible for its cardiotoxicity. Furthermore, there is evidence that the local anaesthetic action on the cardiovascular centre of the brain may make an indirect contribution to the cardiovascular collapse.…”

Levobupivacaine for epidural anaesthesia and postoperative analgesia in hip surgery

“…In addition, Lprilocaine is more rapidly metabolized than its R enantiomer [5]. Electrophysiologic stu dies suggest that the cardiotoxicity of bu pivacaine is mainly due to the Risomer [6]. Central nervous system (CNS) and cardiac toxicity are common to all local anesthetic agents but are of greatest con cern with bupivacaine which shows a long lasting high potency and lipid affinity.…”