Cardiac pacemaker channel (HCN4) inhibition and atrial arrhythmogenesis after releasing cardiac sympathetic activation
| Autor: | Kristine, Chobanyan-Jürgens, Karsten, Heusser, David, Duncker, Christian, Veltmann, Marcus, May, Heidrun, Mehling, Friedrich C, Luft, Christoph, Schröder, Jens, Jordan, Jens, Tank |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Pacemaker Artificial Potassium Channels Adolescent Muscle Proteins lcsh:Medicine Blood Pressure Autonomic Nervous System Article Young Adult Double-Blind Method Heart Rate Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels Humans Ivabradine Prospective Studies cardiovascular diseases lcsh:Science Cross-Over Studies lcsh:R Arrhythmias Cardiac Cardiovascular Agents Kardiovaskuläre Luft- und Raumfahrtmedizin sympathetic and parasympathetic nervous System Cardiovascular and Metabolic Diseases tested cardiovascular system Clinical trials and studies lcsh:Q |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-7 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-26099-9 |
| Popis: | Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test influences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine. Subjects underwent combined head up tilt plus lower body negative pressure testing followed by rapid return to the supine position. In the current secondary analysis with predefined endpoints before data unblinding, continuous finger blood pressure and ECG recordings were analyzed by two experienced cardiac electrophysiologists and a physician, blinded for treatment assignment. The total atrial premature activity (referred to as atrial events) at baseline did not differ between treatments. After backwards tilting, atrial events were significantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. The model in addition to providing insight in the role of HCN4 in human atrial arrhythmogenesis may have utility in gauging potential atrial pro-arrhythmic drug properties. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |