000005430 001__ 5430
000005430 005__ 20170831220334.0
000005430 037__ $$aTAZ-TFM-2010-089
000005430 041__ $$aeng
000005430 1001_ $$aCarro Fernández, Jesús
000005430 24500 $$aAn improved human ventricular cell model for investigation of cardiac arrhythmias under hyperkalemic conditions
000005430 260__ $$aZaragoza$$bUniversidad de Zaragoza$$c2010
000005430 506__ $$aby-nc-sa$$bCreative Commons$$c3.0$$uhttp://creativecommons.org/licenses/by-nc-sa/3.0/
000005430 500__ $$aResumen disponible también en español
000005430 520__ $$aThe use of experiments for studying cardiac arrhythmias or the effect of drugs on cardiac electrophysiology is mostly limited to measurements obtained from electrograms (EGMs, measured on the heart surface) or, more often, electrocardiograms (ECGs, measured on the body surface). Despite the fact that many diagnostic and therapeutical decisions rely only upon interpretation of ECG patterns, the cellular and subcellular mechanisms underlying pathophysiological ECG changes remain mostly unclear. Among the different approaches aimed to connect the ECG with its underlying basis, multi-scale computational modeling of the heart arises as a powerful tool to understand cardiac functioning from the ionic to the whole organ level. With the increase in computational resources available to the scientific community, mathematical modeling and simulation of heart's electrical activity is becoming a fundamental tool to understand cardiac behavior. In this study several modifications were introduced to a recently proposed action potential (AP) cell model so as to render it suitable for the study of ventricular arrhythmias. These modifications were based on new experimental data and in the results of several cellular arrhythmic risk biomarkers reported in the literature. Five stimulation protocols were applied to the original and improved models of isolated cell, and a number of cellular arrhythmic risk biomarkers were computed. The stimulation protocol included a steady-state protocol, abrupt changes in cycle length (CL) protocol, S1S2 and dynamic restitution protocols, and concentration rate dependence protocol. In addition, the behavior of the proposed model under hyperkalemic conditions was simulated in a one dimensional fiber by increasing the extracellular [K+], measuring the AP duration (APD), conduction velocity (CV) and effective refractory period (ERP) after steady-state conditions had been reached. Our modifications led to: a) further improved AP triangulation (78:1 ms); b) APD rate adaptation curves characterized by fast and slow time constants within physiological ranges (10:1 s and 105:9 s); c) maximum S1S2 restitution slope in accordance with experimental data (SS1S2 = 1:0). Under hyperkalemia, our results showed that APD progressively decreased with the level of hyperkalemia, while ERP increased after a threshold in the extracellular [K+] was reached ([K+]o = 6mM). Conduction velocity decreased with hyperkalemia and the conduction was blocked above [K+]o = 10:4 mM. Above [K+]o = 9:8mM, alternans appeared in the APD. These results suggest that the longer ERP values and the conduction block above [K+]o = 10:4mM found in the central zone of acutely ischemic tissue as compared to the normal zone could create areas of block that could set a substrate for reentrant arrhythmias.
000005430 521__ $$aMáster Universitario en Ingeniería Biomédica
000005430 540__ $$aDerechos regulados por licencia Creative Commons
000005430 6531_ $$aHyperkalemia
000005430 6531_ $$aHuman ventricular cell model
000005430 6531_ $$aCardia arrhythmias
000005430 700__ $$aPueyo Paules, Esther$$edir.
000005430 700__ $$aRodríguez Matas, José Félix$$edir.
000005430 7102_ $$aUniversidad de Zaragoza$$bIngeniería Electrónica y Comunicaciones$$cTeoría de la Señal y Comunicaciones
000005430 830__ $$aCPS
000005430 8560_ $$f615309@celes.unizar.es
000005430 8564_ $$s2386590$$uhttps://zaguan.unizar.es/record/5430/files/TAZ-TFM-2010-089.pdf$$yMemoria (eng)$$zMemoria (eng)
000005430 909CO $$ooai:zaguan.unizar.es:5430$$pdriver$$ptrabajos-fin-master
000005430 950__ $$a
000005430 980__ $$aTAZ$$bTFM$$cCPS