Jichu yixue yu linchuang (Jan 2020)
Pantoprazole induces bradyarrhythmia in mice with hypokalemia
Abstract
Objective To investigate the mechanism of arrhythmia induced by pantoprazole (PPZ) in mice with hypokalemia. Methods Mice were randomly divided into control group, PPZ group [20 mg/(kg·d), intraperitoneal injection for 5 weeks], furosemide (FS) group and FS+PPZ group. After 5 weeks, the ECG parameters (heart rate, PR interval, QRS interval, QTc interval) and spontaneous arrhythmia were monitored. The changes of the mRNA and protein expression of hyperpolarization-activated and cyclic nucleotide-cation channels 2 and 4 (HCN2 and HCN4), cardiac voltage-gated sodium channel alpha subunit (SCN5A), L-type calcium channel alpha subunit (CACNA1C) and T-type calcium channel alpha subunit (CACNA1G) were analysed by real-time fluorescence quantitative PCR and Western blot technology. Results Compared with control group, the HR was significantly decreased and PR interval was prolonged in PPZ group (P＜0.01, P＜0.05). Compared with FS group,the HR and PR interval in FS+PPZ group were further decreased and prolonged (P＜0.01, P＜0.05), and 4 mice developed sinus arrest (SA) (P＜0.05). The expressions of HCN4 mRNA and protein in PPZ group were lower than those in control group (P＜0.01), respectively, and the expression in FS+PPZ group was lower than those in FS group (P＜0.01). The expression of HCN2 mRNA in PPZ group was lower than that in control group(P＜0.05), which was further decreased in FS+PPZ group compared with FS group (P＜0.01). Conclusions It is found that pantoprazole may lead to bradyarrhythmia in mice under hypokalemia, which may be related to abnormal expression of HCN2 and HCN4.
