Positive chronotropic effect, of ouabain in the excised and blood-perfused canine SA node preparation of the dog

Summary

The effect of ouabain on the sinus rate was investigated in excised and blood-perfused canine SA node preparations which had 101±3 regular beats/min (mean±S.E., N=46) and 3.2±0.3 ml/min of blood flow through the sinus node artery. When ouabain was rapidly injected in a wide range of doses from 0.3 to 30 μg into the sinus node artery, it caused a dose-dependent acceleration of the regular sinus rate without any latency. The positive chronotropic response to ouabain was not blocked by tetrodotoxin, β-adrenoceptor blocking agents such as propranolol and alprenolol, or pretreatment with reserpine. These observations suggest that the ouabain-induced acceleration is not mediated through adrenergic mechanism. Although a decrease of sinus rate by 7.3±2.3% (mean±S.E., N=6) of the control level was induced by MnCl₂ infusion at a rate of 30 or 60 μg/min, the acceleration response to ouabain was selectively blocked by MnCl₂ while that to noradrenaline was not modified. These results suggest that ouabain causes an increase of influx of Ca ions across the membrane of the SA nodal pacemaker cell, resulting in the acceleration response, and that this increase of Ca ion influx is probably linked with potassium and/or sodium permeability in the slow diastolic depolarization.