ADENOSINE ATTENUATION OF THE ELECTROPHYSIOLOGICAL EFFECTS OF ISOPROTERENOL ON CANINE CARDIAC PURKINJE-FIBERS

Abstract

Adenosine has effects on electrophysiologic parameters of the sinus node, AV node and atrium and antagonizes isoproterenol-induced increased inotropy in the ventricle. The effects on cardiac Purkinje fibers are not well established. The effects of adenosine alone and adenosine on isoproterenol-treated canine cardiac Purkinje fibers were examined. Microelectrode techniques were used to record transmembrane action potentials. Adenosine alone (10-7-10-4 M) produced no effects on action potential characteristics of paced fibers. Adenosine in concentrations of 10-7, 10-6, 10-5 and 10-4 M produced a 15, 24, 44 and 72% attenuation of isoproterenol (10-6 M)-induced action potential duration shortening, respectively (P < 0.001). In 7 of 7 fibers depolarized with 22 mM K+, adenosine (10-4 M) ablated Ca-dependent action potentials restored with isoproterenol (10-6 M). These effects were antagonized by theophylline (5 .times. 10-5 M) and adenosine deaminase (1 U/ml). Action potential shortening due to superfusion of high Ca Tyrode''s solution and Ca-dependent action potentials generated in Na+ free-high Ca2+ Tyrode''s solution were not antagonized by adenosine. Adenosine (10-5 M) produced a negative chronotropic effect, increasing escape intervals from 2669 .+-. 647 to 3702 .+-. 717 ms in control fibers and from 1864 .+-. 329 to 2658 .+-. 399 ms in tyramine (10-4 M)-treated fibers (P < 0.05), but failed to produce a negative chronotropic response in fibers pretreated with propranolol (10-7 M). The following is concluded: adenosine alone does not alter action potential characteristics in paced canine cardiac Purkinje fibers; adenosine antagonizes isoproterenol-induced action potential shortening; adenosine ablates isoproterenol restored Ca-dependent action potentials; and adenosine increases catecholamine-shortened escape intervals in canine cardiac Purkinje fibers. Adenosine antagonizes catecholamine-induced electrophysiologic effects possibly via interaction with an extracellular adenosine Ri receptor.