Three Different Bradycardic Agents, Zatebradine, Diltiazem and Propranolol, Distinctly Modify Heart Rate Variability and QT-Interval Variability
| Autor: | Tetsuo Hadama, Motoko Yamabe, Shinji Miyamoto, Shamarendra Sanyal, Katsushige Ono, Shojirou Isomoto |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Bradycardia medicine.medical_specialty Adrenergic beta-Antagonists Guinea Pigs Propranolol Pharmacology QT interval Diltiazem Electrocardiography Heart Rate Internal medicine medicine Animals Heart rate variability Channel blocker business.industry General Medicine Benzazepines Calcium Channel Blockers Autonomic nervous system cardiovascular system Molecular mechanism Cardiology medicine.symptom business circulatory and respiratory physiology medicine.drug |
| Zdroj: | Pharmacology. 80:293-303 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | 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 (If ); diltiazem is a blocker of the L-type Ca2+ channel (ICaL), and propranolol is a β-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 If channel blocker, had no significant effect on HRV and QTV. Diltiazem, a non-dihydropyridine ICaL 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 β-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. |
| Databáze: | OpenAIRE |
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