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Updated: May 3, 2026
Electromechanical Assessment of Optogenetically Modulated Cardiomyocyte Activity
Published on: March 5, 2020
Pacemaker current inhibition in experimental human cardiac sympathetic activation: a double-blind, randomized,
C Schroeder1, K Heusser2, A A Zoerner2
11] Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany [2] Experimental Clinical Research Center, Charité Medical Faculty and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Abstract:
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.
