000069649 001__ 69649
000069649 005__ 20200221144344.0
000069649 0247_ $$2doi$$a10.1016/j.yjmcc.2016.05.003
000069649 0248_ $$2sideral$$a95026
000069649 037__ $$aART-2016-95026
000069649 041__ $$aeng
000069649 100__ $$0(orcid)0000-0002-1960-407X$$aPueyo, E.$$uUniversidad de Zaragoza
000069649 245__ $$aInteractive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans
000069649 260__ $$c2016
000069649 5060_ $$aAccess copy available to the general public$$fUnrestricted
000069649 5203_ $$aVentricular 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 0.15 Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3-4 minutes 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.
000069649 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/TIN2012-37546-C03-03$$9info:eu-repo/grantAgreement/ES/MINECO/TIN2013-41998-R
000069649 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000069649 590__ $$a5.68$$b2016
000069649 591__ $$aCELL BIOLOGY$$b42 / 189 = 0.222$$c2016$$dQ1$$eT1
000069649 591__ $$aCARDIAC & CARDIOVASCULAR SYSTEMS$$b20 / 126 = 0.159$$c2016$$dQ1$$eT1
000069649 592__ $$a2.536$$b2016
000069649 593__ $$aMolecular Biology$$c2016$$dQ1
000069649 593__ $$aCardiology and Cardiovascular Medicine$$c2016$$dQ1
000069649 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000069649 700__ $$aOrini, M.
000069649 700__ $$aRodríguez, J.F.
000069649 700__ $$aTaggart, P.
000069649 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000069649 773__ $$g97 (2016), 93-105$$pJ. Mol. Cell. Cardiol.$$tJOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY$$x0022-2828
000069649 8564_ $$s257012$$uhttps://zaguan.unizar.es/record/69649/files/texto_completo.pdf$$yPostprint
000069649 8564_ $$s97245$$uhttps://zaguan.unizar.es/record/69649/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000069649 909CO $$ooai:zaguan.unizar.es:69649$$particulos$$pdriver
000069649 951__ $$a2020-02-21-13:51:52
000069649 980__ $$aARTICLE