Author:

Keywords:

Action Potentials, Animals, Bupivacaine, Electric Stimulation, Electrophysiology, Female, Guinea Pigs, Heart, In Vitro, Male, Membrane Potentials, Microelectrodes, Papillary Muscles, Research Support, Non-U.S. Gov't, Stereoisomerism, Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, BUPIVACAINE, ENANTIOMERS, STEREOSELECTIVITY, HEART, GUINEA-PIG PAPILLARY MUSCLE, STANDARD MICROELECTRODE TECHNIQUE, MAXIMAL RATE OF DEPOLARIZATION, VMAX, LOCAL-ANESTHETICS, CARDIOVASCULAR TOXICITY, ANTIARRHYTHMIC DRUGS, SODIUM-CHANNELS, LIDOCAINE, SHEEP, DOG, CARDIOTOXICITY, DEPRESSION, CONDUCTION, In Vitro Techniques, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

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 (Vmax) was reduced to 59.9 +/- 1.4% (n = 10) of control (mean +/- s.e.mean) in the presence of 10 microM 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 Vmax. 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 Vmax and APD in the guinea-pig papillary muscle less than the R(+)-enantiomer at different rates of stimulation and resting membrane potentials.