Mechanism of caffeine-induced arrhythmias in canine cardiac Purkinje fibers.
The effects of caffeine were studied in canine cardiac Purkinje fibers perfused in vitro. The study revealed that (1) caffeine induces an oscillatory potential (Vos) superimposed on early diastolic depolarization in driven fibers; (2) Vos magnitude increases (within limits) with the concentration of caffeine (0.5 to 3 mM) and as a function of time of exposure; (3) if the drive is interrupted, Vos may attain the threshold and initiate spontaneous repetitive activity; (4) caffeine increases the rate of discharge in spontaneously active fibers, also through a Vos; (5) Vos shows the same characteristics as under other conditions of calcium overload; that is, it disappears after a long pause, increases after a shorter pause, can be suppressed by overdrive and can initiate spontaneous discharge at normal or depolarized levels; (7) Vos is dependent on cellular calcium as it appears at lower caffeine concentrations in fibers that are loaded with calcium by increasing extracellular calcium concentration [Ca]o, by decreasing extracellular sodium concentration [Na]o or by administering strophanthidin; (8) caffeine-induced Vos is made to peak sooner and to initiate fast spontaneous rhythms by norepinephrine; (9) Vos is reduced by low [Ca]o but not by propranolol. It is concluded that caffeine causes an oscillatory potential that is modulated by cellular calcium, and this Vos can induce arrhythmias.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D002110:Caffeine / Q000009:adverse effects*; D002118:Calcium / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects / Q000503:physiopathology*
D002110:Caffeine; D002118:Calcium; D009638:Norepinephrine