The pH Dependence on the Electrophysiological Effect of Lidocaine in Ventricular Myocardium. a Computer Modelling Study

Lidocaine is a class I antiarrhytmic drug that blocks the sodium channels. This drug is a tertiary amine and exists as an uncharged free amine and cationic protonated form at physiologic pH. Experimental data have shown that the rate of development and recovery of block is slowed at low pH. In this work, a mathematical model of lidocaine effects has been developed. This model has been incorporated to the Luo Rudy model of guinea pig ventricular action potential and we studied the effect of lidocaine on maximum upstroke velocity (dV/dt), action potential duration (APD), conduction velocity (CV) and effective refractory period (ERP) for different values of pH and concentrations of lidocaine. This study demonstrates that 50 µmol/L of lidocaine reduces the dV/dt 36 % and 71 % as well as the CV a 8 % and 17 % for pH 7.4 and 6.4 respectively, while the ERP was increased 1.8 % and 0.6 % for pH of 7.4 and 6.4. The APD does not change when pH was modulated. 1