Details

Autor(en) / Beteiligte

• Schroeder, C
• Heusser, K
• Zoerner, A A
• Großhennig, A
• Wenzel, D
• May, M
• Sweep, F C G J
• Mehling, H
• Luft, F C
• Tank, J
• Jordan, J

Titel

Pacemaker Current Inhibition in Experimental Human Cardiac Sympathetic Activation: A Double-Blind, Randomized, Crossover Study

Ist Teil von

• Clinical pharmacology and therapeutics, 2014-06, Vol.95 (6), p.601-607

Ort / Verlag

Basingstoke: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Hyperpolarization‐activated, cyclic nucleotide–gated 4 (HCN4) channels 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); 95 6, 601–607. doi:10.1038/clpt.2014.25