Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans.
J Mol Cell Cardiol
; 97: 93-105, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27178727
ABSTRACT
Ventricular repolarization dynamics are crucial to arrhythmogenesis. Low-frequency oscillations of repolarization have recently been reported in humans and the magnitude of these oscillations proposed to be a strong predictor of sudden cardiac death. Available evidence suggests a role of the sympathetic nervous system. We have used biophysically detailed models integrating ventricular electrophysiology, calcium dynamics, mechanics and ß-adrenergic signaling to investigate the underlying mechanisms. The main results were (1) Phasic beta-adrenergic stimulation (ß-AS) at a Mayer wave frequency between 0.03 and 0.15Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3-4minutes of phasic ß-AS, the mean APD adapted and oscillations of APD became apparent. (3) Phasic changes in haemodynamic loading at the same Mayer wave frequency (a known accompaniment of enhanced sympathetic nerve activity), simulated as variations in the sarcomere length, also induced APD oscillations. (4) The effect of phasic ß-AS and haemodynamic loading on the magnitude of APD oscillations was synergistic. (5) The presence of calcium overload and reduced repolarization reserve further enhanced the magnitude of APD oscillations and was accompanied by afterdepolarizations and/or spontaneous APs. In conclusion, low-frequency oscillations of repolarization recently reported in humans were induced by phasic ß-AS and phasic mechanical loading, which acted synergistically, and were greatly enhanced by disease-associated conditions, leading to arrhythmogenic events.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Mecânico
/
Potenciais de Ação
/
Função Ventricular
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Agonistas Adrenérgicos beta
/
Ventrículos do Coração
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Mol Cell Cardiol
Ano de publicação:
2016
Tipo de documento:
Article