抄録
To investigate the mechanism of chlorpromazine (CPZ)-induced ventricular arrhythmia, the changes in ventricular fibrillation threshold (VFT) were followed after intravenous injection of CPZ (1mg/Kg) in dogs. Following injection, VFT was decreased to 56.6±5.4% (mean±SE) of the initial level. Since flavin-adenine-dinucleotide (FAD) combines specifically with CPZ in vitro, we investigate whether or not prior treatment with FAD prevents the CPZ effect. With FAD (2mg/Kg), the CPZ-induced decrease in VFT was significantly cancelled (92.2±4.2% of the initial level). Mitochondria isolated from canine heart after CPZ injection showed a significant decrease in respiratory control index and ADP/O. Effects of CPZ on canine heart mitochondria were also well cancelled by prior administration of FAD. The findings suggest that the arrhythmogenic action of CPZ might be associated in part with impaired function of heart mitochondria. These results also suggest that FAD might be useful in the treatment of the cardiac disturbances associated with overdosage of CPZ
