Stereoselective effects of the enantiomers of bupivacaine on the electrophysiological properties of the guinea-pig papillary muscle.
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.
Vanhoutte
F
F
Laboratory of Clinical Pharmacy, University of Leuven, Belgium.
Vereecke
J
J
Verbeke
N
N
Carmeliet
E
E
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D010210:Papillary Muscles / Q000187:drug effects; D013237:Stereoisomerism
D002045:Bupivacaine