Effects of High Potassium and the Bradycardic Agents ZD7288 and Cesium on Heart Rate of Rabbits and Guinea Pigs

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Abstract
Summary The effects of 2 mM cesium (Cs+ ) and a novel selective bradycardic agent ZD7288 (0.64 μM) on sino-atrial Node (SAN) pacing rate were investigated in an isolated guinea pig SAN/atrial preparation, rabbit SAN preparation, and isolated working rabbit heart preparation. The effect of Cs+ and ZD7288 on the response of the preparations to increased extracellular potassium concentration ([K+]0) was also studied. Cs+ reduced 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 three preparations, increased [K+]0 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 guinea pigs, possibly through modulation of the hyperpolarization-activated current (If). ZD7288 is a more effective bradycardic agent than Cs+.

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