Preclinical Research
The basic hemodynamic, electrophysiological, and pharmacological effects of EGIS‐7229 (E‐7229) were evaluated and compared with those of a pure “Class III“ antiarrhythmic drug (GLG‐V‐13) in conscious rabbits. Both compounds decreased heart rate dose‐dependently. Mean arterial blood pressure was not influenced by E‐7229; however, GLG‐V‐13 produced a significant elevation on this parameter. Left ventricular end‐diastolic pressure was gradually increased by E‐7229, while GLG‐V‐13 induced more considerable elevation on that at intermediate doses. QT and QTcb were lengthened by both compounds; however, higher doses of E‐7229 resulted in shortening of the prolonged QT and QTcb. Ventricular effective refractory period (VERP) was significantly prolonged by either drug studied. Threshold doses to produce QT50%, QTmax, VERP50%, and VERPmax were significantly higher for E‐7229 compared with GLG‐V‐13. Significantly higher doses were required for E‐7229 to induce arrhythmias. The safety ratio was comparable for both of the compounds. E‐7229 can exert multiple actions on cardiac ion channels with minimal influence on hemodynamic parameters and reduced proarrhytmic profile in our preclinical model.