On the mechanism by which caffeine abolishes the fast rhythms induced by cardiotonic steroids.

The abolition by caffeine of the arrhythmias induced by cardiotonic steroids was studied in canine Purkinje and ventricular muscle fibers and in guinea pig ventricular muscle perfused in vitro. Both the electrical and mechanical activity were recorded. The following results were obtained: (1) Caffeine (9 mM) quickly abolished the arrhythmias induced by strophanthidin (10(-6)M) in Purkinje fibers by inducing quiescence at a depolarized level; (2) A lower concentration of caffeine (3 mM) hastened the appearance of the arrhythmias by favoring the onset of spontaneous activity at a depolarized level but abolished the oscillatory potential at lower strophanthidin concentrations (2-5 X 10(-7)M); (3) Caffeine (9-10 mM) abolished the oscillatory potentials and after-contractions induced by cardiotonic steroids in ventricular muscle fibers; (4) Caffeine prevented the induction of oscillatory potentials and of arrhythmias by cardiotonic steroids; (5) In the presence of cardiotonic steroids and norepinephrine, the oscillatory potentials can induce fast discharge in myocardial fibers which is eliminated by caffeine; (6) High calcium and norepinephrine (singly or together) induce oscillatory potentials and after-contractions which are abolished by caffeine; (7) The elimination of the oscillatory potentials by caffeine in myocardial fibers is associated with the development of contracture. It is concluded that caffeine eliminates cardiac steroid-induced arrhythmias by quickly depolarizing Purkinje fibers and by eliminating the oscillatory potentials in myocardial fibers and (at suitable concentrations) also in Purkinje fibers.