Abstract

The effects of lidocaine (25,50 and 100 μg/ml) and bupivacaine (5,10, and 20 μg/ml) on amplitude, velocity, and contraction frequency were studied in monolayer cultures of spontaneously beating chick embryo ventricular cells. The physiologic parameters of contraction frequency, amplitude, and velocity of shortening were measured with an optical-video system. Studies were also carried out in the presence of 1μM tetrodotoxin (TTX) to isolate effects caused by TTX-sensitive ion channel blockade from other possible mechanisms of action of local anesthetics. Lidocaine and bupivacaine produced concentration-dependent, reversible decrements in contraction frequency, amplitude, and velocity of contraction. Bupivacaine demonstrated a 5-fold higher potency for depression of contractile properties than lidocaine. At a high concentration, bupivacaine (20 μg/ml) produced significantly more depression in all three measured parameters than did lidocaine (100 μg/ml). In the presence of predominantly Na⁺ channel blockade by TTX, bupivacaine (10 μg/ml) produced further decreases in amplitude and velocity of shortening. In the presence of TTX, lidocaine (50 μg/ml) produced a further decrease in amplitude of contraction, but no significant change in contraction frequency or velocity of contraction. It is well known that local anesthetics block Na⁺ channels of excitable membranes. The authors observations suggest that both lidocaine and bupivacaine have at least one locus of action at a site other than a TTX blockade site.