Pacemaker current inhibition in experimental human cardiac sympathetic activation: a double-blind, randomized, crossover study.
Clin Pharmacol Ther
; 95(6): 601-7, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24509430
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Marca-Passo Artificial
/
Sistema Nervoso Simpático
/
Coração
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2014
Tipo de documento:
Article