Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine.
The effects of local anesthetics in depressing myocardial contractility were studied in isolated guinea pig right ventricular papillary muscles. Bupivacaine and etidocaine, 4 and 10 microM, showed reverse frequency-dependent depression of contractility, that is, less significant depression of contractility at higher stimulation frequencies (2-3 Hz) than at lesser frequencies (less than 1 Hz). Lidocaine, 40 microM, demonstrated a similar trend. In contrast, the normal action potential maximum rate of depolarization (Vmax), a measure of sodium channel conductance, was significantly more depressed at 2-3 Hz by bupivacaine and etidocaine than by lidocaine. Consequently, contractile depression could be overcome only at higher stimulation frequencies, at which conduction was depressed. To explore the mechanism of the contractile depression, local anesthetic effects were studied on slow (calcium channel-mediated) action potentials in partially depolarized papillary muscles. Etidocaine and bupivacaine, 4 and 10 microM, and lidocaine, 40 and 100 microM, caused a marked depression of the late-peaking contractile responses, attributed to Ca2+ release from the sarcoplasmic reticulum. In contrast, only 10 microM bupivacaine caused any significant depression of the slow action potential rate of depolarization (to 89% of control), consistent with a possible small depression of Ca2+ entry.
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D000083:Acetanilides / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D003864:Depression, Chemical; D004558:Electric Stimulation; D005041:Etidocaine / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*
D000083:Acetanilides; D007473:Ion Channels; D008012:Lidocaine; D005041:Etidocaine; D002045:Bupivacaine