Mechanical and electrophysiological effects of mepivacaine on direct myocardial depression in vitro.
The effects of various concentrations (20, 50, and 100 mumol litre-1) of mepivacaine were studied in isolated guinea pig and rat right ventricular papillary muscles by measuring the effects on myocardial contractility and electrophysiological parameters. Mepivacaine produced dose-dependent depression of peak force during 0.5 to 3 Hz stimulation rates in guinea pig papillary muscles. Conduction block was frequently noted, especially at higher stimulation rates (2 and 3 Hz) with mepivacaine 50 and 100 mumol litre-1. In rat papillary muscle experiments, about 20% depression of peak force was shown at rested state contraction. Shortening of action potential (AP) duration (APD50: about 10%, APD90: about 10%) and rate-dependent depression of dV/dt max was observed with mepivacaine 100 mumol litre-1. In 26 mmol litre-1 K+ Tyrode's solution, mepivacaine 50 and 100 mumol litre-1 produced a dose-dependent depression of early (50 mumol litre-1: about 20%, 100 mumol litre-1: about 30%) and late (50 mumol litre-1: about 30%, 100 mumol litre-1: about 50%) force development. In slow APs, neither shortening of AP duration nor changes of dV/dt max were shown by mepivacaine 100 mumol litre-1. An approximate 30% depression of contracture induced by rapid cooling after 2 Hz stimulation rates was observed with mepivacaine 100 mumol litre-1. It may be concluded that the direct myocardial depressant effect of mepivacaine is likely to be caused by inhibition of Ca2+ release from the sarcoplasmic reticulum. The Na+ channel blocking action may contribute indirectly to the depression of contractility.
Park
W K
WK
Department of Anesthesiology, Yonsei University College of Medicine, Seoul, Korea.
Suh
C K
CK
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003470:Culture Media; D046508:Culture Techniques; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D007036:Hypothermia, Induced; D007552:Isotonic Solutions; D008619:Mepivacaine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000779:Anesthetics, Local; D003470:Culture Media; D007552:Isotonic Solutions; C037692:Tyrode's solution; D008619:Mepivacaine