Illustrative brain karyopyknotic cell microscopic presentation (HE staining; magnification 400× (a–d), scale bar 100 μm; magnification 600× (e–p), scale bar 50 μm) in the sotalol control rats assessed following application of sotalol, given therapy application at 15 min (a,e,i,m) (period 0–15 min), at 90 min (b,f,j,n) (period 0–90 min) and at 180 min (c,g,k,o) (period 0–180 min) or at 180 min (d,h,l,p) (period 90–180 min). Saline medication was given as an early application immediately after sotalol (a,b,d,e,g,h), or as delayed post-treatment (at 90 min and assessment at 180 min sotalol-time) (d,h,l,p). An increased number of karyopyknotic cells was found in all four areas of the brain (cerebrum, hippocampus, hypothalamus, cerebellum) (black arrows and marked areas). An increased number of karyopyknotic cells was shown in the cerebrum and cerebellum with an early regimen at the end period of 15, 90, and 180 min (a–d) sotalol-time. In the hippocampus and hypothalamus, no karyopyknotic cells were observed with an early regimen at the end period of 30 min sotalol-time. An increased number of karyopyknotic cells was found in these two areas of the brain at the end period of 90 and 180 min sotalol-time.