LAUSR

Even though rodents are accessible model animals, their electrophysiological properties are deeply different from that of human, making the translation of rat studies to human rather difficult. We compared the mechanisms of ventricular repolarization in various animal models to those of human by measuring cardiac ventricular action potentials from ventricular papillary muscle preparations using conventional microelectrodes, and applying selective inhibitors of various potassium transmembrane ion currents. Inhibition of the IK1 current (10 µM barium chloride) significantly prolonged rat ventricular repolarization, but only slightly prolonged it in dog, and did not affect it in human. On the contrary, IKr inhibition (50 nM dofetilide) significantly prolonged repolarization in human, rabbit, and dog, but not in rat. Inhibition of the IKur current (1 µM XEN-D0101) only prolonged rat ventricular repolarization, and had no effect in human or dog. Inhibition of the IKs (500 nM HMR-1556) and Ito currents (100 µM chromanol-293B) elicited similar effects in all investigated species. We conclude that dog ventricular preparations have the strongest, and rat ventricular preparations have the weakest translational value in cardiac electrophysiological experiments.