The Effects of Antiarrhythmic Drugs, Stimulation Frequency, and Potassium‐Induced Resting Membrane: Potential Changes on Conduction Velocity and dV/dtmax in Guinea Pig Myocardium

For one-dimensional propagation, a nonlinear relationship between Vmax and conduction velocity is predicted by cable theory, and, under experimental conditions, Vmax and conduction velocity may change in opposite directions. Using standard microelectrode techniques, we have measured Vmax and conduction velocity in guinea pig papillary muscles exposed to tetrodotoxin and low sodium (agents expected primarily to decrease, directly, the rapid inward current), increased extracellular potassium (an agent which decreases the rapid inward current at least partially by inactivation mediated by depolarization of the resting membrane potential), and, over a wide range of stimulation frequencies, the antiarrhythmic drugs, quinidine, lidocaine, and procainamide. In all cases, except for the region of potassium-induced “supernormal conduction” between 5.4 and 9 mM, Vmax and conduction velocity varied as predicted by one-dimensional cable theory; that is, changes in Vmax were always proportional to changes in the square of conduction velocity. We conclude that the relationship between Vmax and conduction velocity predicted by cable theory occurs experimentally in guinea pig papillary muscle subjected to commonly used antiarrhythmic drugs and other interventions expected to reduce the sodium inward current. This relationship may be useful in applying known effects of drugs on Vmax to action potential propagation.

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