ISSN:
1432-1912
Keywords:
Lidocaine
;
Tocainide
;
Cardiac action potential
;
Reactivation of $$\dot V_{\max } $$
;
Computer simulation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Effects of lidocaine and tocainide on transmembrane potentials were studied in isolated guineapig papillary muscles, superfused with modified Tyrode's solution containing either 5.4, 2.7, 10.0 or 8.1 mmol/l potassium concentration, [K]0. The last solution applied contained either 1.8 (normal [Ca]0) or 7.2 mmol/l [Ca]0) (high [Ca]0). The concentrations of lidocaine and tocainide used were 18.5, 36.9 and 73.9 μmol/l and 43.7, 87.5 and 174.9 μmol/l in 5.4 mmol/l [K]0 solution and 36.9 and 87.5 μmol/l in the other solutions, respectively. At the driving rate of 1 Hz in 5.4 mmol/l [K]0 solution, both drugs produced dosedependently a reduction of maximum rate of rise of action potential ( $$\dot V_{\max } $$ ), together with a prolongation of the relative refractory period. $$\dot V_{\max } $$ decreased progressively as the driving rate was increased from 1 Hz (for lidocaine) and from 0.25 Hz (for tocainide) to 5 Hz. This action was accentuated dose-depently. A slow component (time constant τ=195–232 ms for lidocaine, 281–303 ms for tocainide) and slower component (τ=2.1–3.8 s for tocainide) of the recovery (reactivation) of $$\dot V_{\max } $$ were observed in premature responses at 0.25 Hz and in the first response after interruption of the basic driving rate at 1 Hz. All these effects were accentuated with rising [K]0 and attenuated in the high [Ca]0 solution. Both drugs abbreviated the action potential duration at 50% (APD50) and 90% (APD90) levels at 5.4, 8.1 and 10.0 mmol/l [K]0 but not at 2.7 mmol/l [K]0 nor a high [Ca]0 at 1 Hz. These [K]0-dependent effects of lidocaine on $$\dot V_{\max } $$ were successfully simulated by the model proposed by Hondeghem and Katzung (1977), with a slight change in parameter values. The mode of interaction of lidocaine with sodium channels in the open, closed and rested states was deduced from these results.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00498433
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