Modelling the Effects of Hypertension on Ventricle Cells of Human Heart

Abstract

Systemic hypertension (HP) is one of the key risk factors for evolving cardiac hypertrophy and heart failure (HF). Previous studies have shown that cardiac hypertrophy is associated with altered excitation-contraction (E-C) coupling and enhanced myocardial contraction, whilst HF is associated with diminished contractility.This study aimed to investigate the functional impact of hypertension on the cardiac mechanical dynamics and the contracting mechanisms of the left ventricular myocytes of human heart. An electromechanical model of human ventricular cell model developed by Adeniran et al. has been modified by incorporating available experimental data from rat ventricular cells under Sham (control) and HP conditions. Hypertrophy was modeled by incorporating experimental data of changes in I Na , I to , I NaCa , cell size and myofilament responses to Ca 2+ in the cardiac cell.Simulations showed that HP produced:1) prolongation of the action potential duration at 90% repolarization (APD 90 ) by approximately 4.7%; 2) an increase of the intracellular calcium concentration ([Ca 2+ ] i ) by 36%; 3) no marked change in the sarcomere length or the contractile force. Simulation results were consistent with experimental data, validating the HP model development and indicated the pro-arrhythmic effects of HP.