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)