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Pacemaker Current Inhibition in Experimental Human Cardiac Sympathetic Activation: A double-blind, Randomized, Crossover Study.
MedLine Citation:
PMID:  24509430     Owner:  NLM     Status:  Publisher    
Hyperpolarization-activated cyclic nucleotide-gated 4 channels (HCN4) comprise the final pathway for autonomic heart rate (HR) regulation. We hypothesized that HCN4 inhibition could reverse autonomic imbalance in a human model of cardiac sympathetic activation. Nineteen healthy men ingested oral metoprolol+reboxetine, ivabradine+reboxetine, or placebo+reboxetine in a double-blind, randomized, crossover fashion. We assessed HR, blood pressure (BP), stroke volume, and cardiac output during rest and profound orthostatic stress. HR variability, BP variability, and baroreflex sensitivity were analyzed. Metoprolol, but not ivabradine, decreased resting HR and BP. Ivabradine attenuated the HR increase to orthostatic stress, albeit to a lesser extent than metoprolol. Stroke volume and cardiac output at a given HR were significantly lower with metoprolol. Unlike metoprolol, ivabradine did not affect HR variability, BP variability, or baroreflex sensitivity. Ivabradine attenuates sympathetic influences on HR at the sinus node level, leaving myocardial sympathetic activation unopposed. Reversal of parasympathetic dysfunction by ivabradine appears limited.Clinical Pharmacology & Therapeutics (2014); accepted article preview online 7 February 2014 doi:10.1038/clpt.2014.25.
Christoph Schroeder; Karsten Heusser; Alexander A Zoerner; Anika Großhennig; Daniela Wenzel; Marcus May; Fred C G J Sweep; Heidrun Mehling; Friedrich C Luft; Jens Tank; Jens Jordan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-2-07
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  -     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2014 Feb 
Date Detail:
Created Date:  2014-2-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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