EFFECTS OF HIGH POTASSIUM AND THE BRADYCARDIAC AGENTS ZD7288 AND CESIUM ON HEART-RATE OF RABBITS AND GUINEA-PIGS

The effects of 2 mM cesium (Cs+) and a novel selective bradycardic age nt ZD7288 (0.64 mu M) on sinoatrial Node (SAN) pacing rate were invest igated in an isolated guinea pig SAN/atrial preparation, rabbit SAN pr eparation, and isolated working rabbit heart preparation. The effect o f Cs+ and ZD7288 on the response of the preparations to increased extr acellular potassium concentration ([K+](o)) was also studied. Cs+ redu ced beating frequency by 24% in isolated rabbit SAN (n = 16, p < 0.01) and by 21% in isolated working rabbit heart(n = 9, p < 0.01). ZD7288 decreased beating rate by 53% in guinea pig SAN (n = 7, p < 0.01) and by 38% in isolated working rabbit heart (n = 6, p < 0.01). In all thre e preparations, increased [K+](o) significantly decreased the rate (p < 0.01) in normal Tyrode's solution but had no effect in the presence of Cs+ and caused tachycardia (p < 0.01) in the presence of ZD7288. We conclude that Cs+ and ZD7288 decrease pacing rate in rabbits and guin ea pigs, possibly through modulation of the hyperpolarization-activate d current (I-f). ZD7288 is a more effective bradycardic agent than Cs.