LAUSR

24hr recording with RE. We observed expected drug-related changes in QTcF and JTpc intervals in L2 and VM. We did not observe shortening of JTpc relative to QTcF for Verapamil and Mexiletine, but we did see over 2x the percentage increase in TpTe vs JTpc for Verapamil and nearly 2x percentage increase with Mexiletine. High doses of Dofetilide are associated with arrhythmias typical of hERG channel blockade, consistent with our arrhythmia observations. High doses of Verapamil are known to be associated with PR prolongation and AV block. Our high doses of Verapamil produced varying degrees of AV block and related arrhythmias with no obvious PR prolongation (PR interval not shown). Brockway et. al. previously found that the VM lead provided more consistent results in canine model5. In this study of an NHP model, VM and L2 provide similar results. The superiority of VM vs. L2 in the prior study on a canine model may have been due to changes in electrical axis during respiration and changes in posture. Superiority was especially prominent in the canine model when T-waves were biphasic. VM has the effect of mitigating changes in QRS and T-wave morphology observed due to the change in electrical axis, effectively computing a global lead that provides a composite of all dipolar electrical activity of the heart. We hypothesize that if the test article induced biphasic Twaves in NHP, VM may prove superior in that model as well. The RE software facilitated effective ECG baseline correction, which is critical to derivation of a VM lead and accurate measurements of JTp and TpTe intervals. Use of multiple ECG leads facilitates improved detection accuracy for Ventricular Ectopic (VE) beats where differences between Normal and VE beats are subtle as seen with Dofetilide. Ongoing studies with Dofetilide+Verapamil and Dofetilide+Mexiletine will provide further insights into the ability to differentiate multi-channel block.