三種治療心律不整的藥(Zatebradine, Diltiazem, Propranolol)都會降低心跳,但對HRV及心電圖QT間距變化(QTV)截然不同; Zatebradine為極化電流阻斷劑,對HRV及QTV沒有影響; Diltiazem為鈣離子阻斷劑,它會增加HF(副交感)及QT間距,且降低LF/HF; Propranolol為Beta阻斷劑,它會降低LF(交感),LF/HF,及QT間距

Three different bradycardic agents, zatebradine, diltiazem and propranolol, distinctly modify heart rate variability and QT-interval variability.

Pharmacology. 2007; 80(4):293-303 (ISSN: 1423-0313)

Yamabe M; Sanyal SN; Miyamoto S; Hadama T; Isomoto S; Ono K
Department of Cardiovascular Science, Oita University School of Medicine, Oita, Japan.

Zatebradine, diltiazem and propranolol are all antiarrhythmic agents, and all induce bradycardia, but each is known to have a different initial molecular mechanism: zatebradine is a channel blocker of the hyperpolarization-activated inward current (I(f)); diltiazem is a blocker of the L-type Ca(2+) channel (I(CaL)), and propranolol is a beta-blocker. To further investigate the mechanisms underlying their clinical effects, we studied their effects on heart rate variability (HRV) and QT-interval variability (QTV). To this end, guinea pigs were treated with either zatebradine (1.5 mg/kg, i.p.), diltiazem (40 mg/kg, i.p.) or propranolol (20 mg/kg, i.p.). A dose of each agent that decreased HR by 20-22% was used in this study. HRV and QTV were analyzed by a fast Fourier and/or a wavelet transform algorithm. Zatebradine, an I(f) channel blocker, had no significant effect on HRV and QTV. Diltiazem, a non-dihydropyridine I(CaL) blocker, increased high frequency (HF) power and decreased the power ratio of the low frequency (LF) range to the HF range (L/H) in HRV, and increased QTV. Propranolol, a non-selective beta-antagonist, decreased LF power and L/H ratios in HRV, and appreciably reduced QTV. These differences in pharmacological action may help us better understand the antiarrhythmic and/or proarrhythmic actions of these agents when they are used clinically for reducing HR.