Chronotropic action of alinidine on the isolated sinus node of the rabbit heart.

The main action of alinidine, proposed for the treatment of angina pectoris, is a reduction of heart rate. To evaluate this negative chronotropic action, we studied the effect of the drug (concentrations ranging from 0.57 to 29 X 10(-6) M) on sinus rate and pacemaker location by multiple intracellular impalements in 31 isolated rabbit right atria. Alinidine caused a dose-dependent prolongation of the spontaneous cycle length which amounted to 58 ms +/- 28 (13% +/- 7) (+/- 1 SD) compared with control at 2.9 microM. Corrected sinus node recovery time increased from 83 ms +/- 47 to 126 ms +/- 80. Higher concentrations did not further increase the cycle length. The bradycardiac action was due to a selective slowing of phase 4-depolarization of pacemaker fibres. Amplitude and duration of the transmembrane potential of dominant fibres remained unchanged. However, repolarization of latent and atrial fibres was prolonged. Atrial effective refractory period increased by about 10%. The electrophysiologic effects of clonidine in equimolar concentrations were similar to alinidine. This study identifies slowing of phase 4-depolarization of dominant fibres as cause of the negative chronotropic action of alinidine. Pacemaker location and sinoatrial conduction time were unaffected.