chapter  4
18 Pages

Chapter 4

ByEnrique Chacon, Joseph W. Starnes, Vivek Kadambi

The ever-increasing number of chemical compounds synthesized by chemical

and pharmaceutical industries has prompted the development of innovative in

vitro research methods for optimizing potential drug candidates. Many of these

new approaches show promise for effective and inexpensive toxicity assessment.

In addition to providing potential toxicity assessments, in vitro methods serve as

ideal models to investigate and understand mechanisms of action. In the previous

edition (1), we discussed in vitro cytotoxicity modeling and the credence of in

vitro models. Three important criteria need to be considered in the selection of

an in vitro method are (i) the assay must correlate well with the in vivo biological

response being modeled; (ii) the assay must have a biological basis that links it to

the cell injury or pharmacological process; and (iii) the assay should be tech-

nically reliable and reasonably easy to conduct if used for screening purposes. In

this chapter, we present a summary of the use of cardiac myocytes and two

newer approaches being used to assess cardiotoxicity. Specifically, the two new

models presented are the working heart model to evaluate cardiovascular toxicity

and hERG channel assessment to evaluate QT interval prolongation.