Chronotropic effect of cardiac glycosides in cats, dogs, and rabbits.

We have tested the widely accepted hypothesis that digitalis, in nontoxic concentration, can act directly on cells of the sinoatrial pacemaker to cause slowing. The effect of autonomic nerves on sinoatrial cells was eliminated either by chronic cardiac denervation or by use of autonomic blocking agents such as atropine, 0.5 mg/kg, and propranolol, 2 mg/kg, or MJ-1999, 3 mg/kg. When the effects of autonomic nerves were eliminated, acetylstrophanthidin, 0.120 mg/kg, failed to cause slowing of sinus rate in the anesthetized cat and the anesthetized dog. Similarly, ouabain, 5 x 10-7M, and acetylstrophanthidin, 1.5 µg/ml, after prior administration of autonomic blocking agents failed to cause slowing of the isolated rabbit right atrium perfused with Tyrode's solution. These results indicate that the sinus slowing caused by cardiac glycosides may be mediated entirely by alteration of the neural control of the heart and that the drug, in nontoxic concentration, does not have a direct negative chronotropic action...