RT Journal Article
SR Electronic
T1 THE CHRONOTROPIC EFFECT OF DIGITALIS STUDIED BY DIRECT PERFUSION OF THE SINUS NODE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 42
OP 52
VO 139
IS 1
A1 Thomas N. James
A1 Reginald A. Nadeau
YR 1963
UL http://jpet.aspetjournals.org/content/139/1/42.abstract
AB A new experimental model permitting direct perfusion of the sinus node was employed in a study of the chronotropic effect of digitalis in 35 dogs. The three digitalis preparations investigated were acetylstrophanthidin, digoxin and lanatoside C. Utilizing doses of approximately 1/1000th the systemic amount, it was possible to "digitalize" the sinus node by a 2-minute perfusion, this being followed by immediate and continued autoperfusion of the node by the animal with its own arterial blood. With a 2-minute perfusion of 0.5 to 1.0 µg/ml of acetylstrophanthidin definite chronotropic effects of digitalis were observed. Of these effects sinus bradycardia was the commonest, bradycardia followed by tachycardia (and the reverse) the next most common, and tachycardia (only) the least common. Sinus arrest with A-V nodal escape rhythm was observed the same number of times as tachycardia alone. Dividing these into negative and positive chronotropic responses, the negative responses were about half again as common as positive ones. Both types of response were not only observed in the same dog, but often in sequence during the same experiment. Prior administration of atropine or bilateral cervical vagotomy did not prevent the negative chronotropic effect of digitalis, nor did these procedures alter such a response once established. Appearance of a chronotropic effect from digitalis was often delayed in onset until several minutes after completion of the perfusion into the sinus node. Since autoperfusion with the animal's own blood continued in this period, the significance relative to time of fixation, lack of washout, and related questions have been considered. Except for duration of action, there was no remarkable difference in the types or frequency of various chronotropic effects from the three preparations studied. The duration of action from direct perfusion of the sinus node was comparable for each preparation to its duration of action when given systemically. Reversal of digitalis effect by both normal saline and epinephrine was observed. Possible mechanisms of this reversal are discussed.