| Effect of verapamil and bupivacaine alone or in combination of both on the nerve conduction in isolated rat sciatic verve preparation. |
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Byoung Sang Lee, Byung Jung Kim, Hyun Choi, Sung Woo Lee, Ho Yeong Kil, Young Joon Yoon |
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Department of Anesthesiology, Hallym University Medical School, Seoul, Korea. |
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| Abstract |
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Racemic verapamil has been shown to have local anesthetic activity, and fast sodium channel blockade is responsible for its inhibitory effect on nerve conduction. This study de- scribes the dose response inhibition of nerve conduction hy verapamil and bupivacaine alone as well as in combination of both on an isolated rat sciatic nerve preparation. In addition, it describes the effect of caleium ion concentration on this in vitro nerve preparation. Sciat- ic nerve preparation from rats were placed in mammarian ringer solution(MRS) adjusted to pH 7.4 at 22degrees C. Each nerve was mounted in a nerve conduction chamber containing MRS in the presence of verapamil(10-5M-2X10-3 M), bupivacaine(10-6M-10-3M) or a combination of both. Each nerve was stimulated with a square wave pulse at twice threshold potential(4 -7V), 0.02msec of duration, 10Hz of frequency. Compound action potentials(CAP) were photographed and measured on a Tektronix oscilloscope. The nerve was first equilibrated in the nerve conduction chamber in MRS, (pH 7.4, 22degrees C for 30min) and CAP was recorded for control(100% recovery). Then, the nerve was exposed to increasing concentrations of verapamil and bupivacaine for 12 minutes and a CAP was measured after each exposure. All CAP were compared to the control CAP and the results were expressed as a % of control CAP. We got dose response curve of verapamil, bupivacaine and combination of both. Also, we determined EC 25%, 50%, 75% from these data(EC % : Effective concentra- tions of drug for % CAP inhibition). Each of the experiments was performed on at least 4 nerves and differences between groups were analyzed using ANOVA test.
Verapamil is shown to inhibit nerve conduction with an EC 25% = 2.2X10-4M, EC 50%=3.8X10-4M, EC 75% =6.3X10-4M and EC 50% for bupivacaine was 5.0X10-5 M. When verapamil dose response curves were performed in the presence of a wide range of CaCl2 containing MRS solutions, there was no significant differences in the response curve(P>0.05). In conclusion, racemic verapamil was shown to have dose dependent local anesthetic activity with a relative potency of 1/8 of bupivacaine. When combined with bupivaeaine, local anesthetic activity inereased in an additive manner. This suggests that these two drugs act on the nerve membrane in a similar fashion. Various CaCl2 concentrations have no effect on nerve conduction inhibition of verapamil. This implicates sodium channel blockade as the mechanism of local anesthetic activity of verapamil. |
| Key Words:
Verapamil; Fast channel blockade; Local anesthetic activity |
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