Cardiac Action Potential Kinetics (APD)

Purpose

By analyzing changes in the morphology of the ventricular action potential, this assay verifies the direct interaction of a test article with all the channels involved in AP generation, and can point to the to the population of channels affected in the characteristics such as rate-dependence and pathological effects such as hypokalemia, hypothermia, etc.

Method

– Number of tissues exposed to the test article: 5 tissues (screens 3 )
– Number of concentrations of test article tested: 4 (screens 3 )
– The model is easily adapted to reproduce disease characteristics of interest
– Stimulation pattern: Electric field stimulation, variable frequencies of stimulation
– A study includes positive, negative, and vehicle controls

Study Outcome

– A quantitative assessment of multiple-channel interactions (MICE) with the test article
– Analytical dissection of the AP in pharmacologically relevant segments :VRest, VMax,  dV/dt, APD30, APD60 and APD90, APD90-30
– Analysis of the incidence of triangulation, reverse-rate dependence, early-afterdepolarization events
– FDA-ready hard copy  and e-report for electronic IND submission
– Holistic interpretation of a positive signal, considering all other data generated

Compliance

Pre-IND (GLP-compliant ) or exploratory designs (non-GLP compliant)

Species

Rat, guinea-pig, rabbit, dog hearts