In Vivo Telemetry Capabilities and Preclinical Drug Development

Optical AP measurements using voltage-sensitive dyes (i.e., ANEPPS dyes) are also commonly used (Herron et al., 2012 Leyton-Mange et al., 2014). Changes in optical measurement of AP duration closely reflect prolonged or shortened AP/FPD/QT interval (Fig. 9.5) (Ian Spencer et al., 2014). 

In many of the above assays, other parameters including heat rate, amplitude and slope of the upstroke, and incidence of arrhythmias could he also measured. However, the translational value of these parameters to in vivo or man still needs to be further investigated. 

Video microscopy image-based analysis (phase-contrast video microscopy) in combination with MEA or Ca transient measurements can also be used for drug safety screening (Hayakawa et al, 2014), although this assay is still under early investigation. 

FIGURE 9.5 Schematic drawing of the relationship between cardiac action potential duration (APD) and the duration of the QT interval on the surface electrocardiogram (ECG) or the field potential duration from multielectrode array (MEA) recordings (top three parts of the figure) lower panel shows a schematic of the relationship between the calcium transient, APD, and contraction on hiPSC-CMs. 

5 IN VIVO TELEMETRY CAPABILITIES AND PRECLINICAL DRUG DEVELOPMENT 

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