title: Three different bradycardic agents, zatebradine, diltiazem and propranolol, distinctly modify heart rate variability and QT-interval variability.
abstract: 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.
authors: Department of Cardiovascular Science, Oita University School of Medicine, Oita, Japan.
authors: Motoko
authors: M
authors: Yamabe
authors: Shamarendra N
authors: SN
authors: Sanyal
authors: Shinji
authors: S
authors: Miyamoto
authors: Tetsuo
authors: T
authors: Hadama
authors: Shojirou
authors: S
authors: Isomoto
authors: Katsushige
authors: K
authors: Ono
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011433:Propranolol / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002121:Calcium Channel Blockers; D011433:Propranolol; D004110:Diltiazem; C043636:zatebradine