3.2 Effects of testosterone on the QT interval of animals
Testosterone has been shown to be a major factor contributing to the
shortening of the QTc interval and lowering the risk of TdP in a variety
of animal models (3). Similarly, to humans QTc shortening can occur
through the upregulation and downregulation of ion channel expression
and function in the presence of testosterone (Table 2 ). Several
animal models were considered for this study and showed a trend in
concordance with human studies. In adult male and female rabbits,
testosterone shortens the length of the APD as well as decreases the
susceptibility to arrhythmogenesis and triggered activity (43–45).
Following this trend, rat models in a testosterone deficient state
presented with QT prolongation, which could be restored to normal by
testosterone administration (1). For instance, Lujan et al (46),
showed that ORCX rats have longer QT intervals than normal rats.Table 2 presents an extensive list of animal models and results
further supporting the inverse relation between testosterone and the QT
interval.
Table 2. Biochemical effect of testosterone on animals
(43,44,47–71)