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 dose-dependent 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 measurements 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.