The influence of a new cardiotonic drug, acrihellin, on sinus node and the current underlying pacemaker activity of cardiac Purkinje fibres.
The spontaneous beating frequency of guinea pig sino-atrial preparations was observed under the influence of 3 beta, 5, 14-trihydroxy-19-oxo-5 beta-bufa-20,22-dienolide-3-(3-methylcrotonate (D 12316, acrihellin), a new cardiotonic drug. There was a slight acceleration of spontaneous frequency after administering rather high doses (10(-6) mol/l) of the drug. Voltage clamp experiments were performed in sheep cardiac Purkinje fibres. AcriheLlin strongly affected the current underlying pacemaker activity, ik2. The kinetic parameter s infinity of this current system was shifted in the hyperpolarizing direction by 4-13 mV. The amplitude of the pacemaker current in Purkinje fibres was reduced by up to 25% in voltage clamp experiments, but the reversal potential and the inward going rectification were left unchanged. After exposure to adrenaline (epinephrine) the well-known depolarizing shift of s infinity was partially restored by acrihellin. This can be interpreted as an antiadrenergic effect of the drug similar to that of beta-adrenoceptor antagonists. However, beta-blockers do not affect the pacemaker kinetics of fibres untreated with adrenaline as does acrihellin. This suggests that the interplay of acrihellin and adrenaline is not that of an agonist and antagonist at a membrane receptor but rather the overlapping of two separate membrane effects.
D000818:Animals; D002018:Bufanolides / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D011690:Purkinje Fibers / Q000187:drug effects*; D012756:Sheep; D012849:Sinoatrial Node / Q000187:drug effects*
D002018:Bufanolides; D002316:Cardiotonic Agents; C039328:acrihellin; D004837:Epinephrine