Modulation of cardiac impulse generation and conduction by nifedipine and verapamil analyzed by a refined surface ECG technique in Langendorff perfused guinea pig hearts

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Abstract
Using a modified Langendorff system, a special ECG recording technique and appropriate placement of two silver wire electrodes, early atrial and His bundle activity can be detected continuously from the surface of intact and spontaneously beating guinea pig hearts. This new method was applied to measure the direct and inhibitory effects of nifedipine and verapamil on impulse generation and conduction in isolated and perfused guinea pig hearts. Depression of sinoatrial conduction was the most prominent effect of nifedipine. In all concentrations applied (10−7 M, 10−6 M, 10−5 M) nifedipine predominantly led to sinoatrial blocks of different degrees. Heart rate decreased slightly in a dosedependent manner. PQ and HV duration remained essentially constant. In the highest concentration of nifedipine (10−5 M), sinus node activity was so depressed that AV dissociation or ventricular rhythm developed. Only in one out of eight experiments with cumulative increase of nifedipine concentrations to 10−5 M was the AV node affected by nifedipine and a second-degree AV block developed (10−6 M). Verapamil's inhibitory effects on the rate of impulse initiation in the sinus node were more pronounced than those of nifedipine, but the inhibition of sinoatrial conduction by verapamil was less marked. At 10−6 M verapamil, the incidence of sinoatrial blocks and of ventricular rhythm was similar to the incidence of first degree AV blocks. PQ time (+14%) but also HV time (+12%) were prolonged under the influence of this concentration of verapamil. At the highest concentration of verapamil (10−5 M) applied for 10 min, ventricular rhythm developed in five out of eight experiments, as well as one second and two third-degree AV blocks. The results confirm that the simultaneous measurement of sinus node activity of sinoatrial and atrioventricular conduction and of HV duration is feasible with this ECG technique, to evaluate the inhibitory effects of Ca-antagonists on sinus and AV node activity in the intact heart.