Reduced Myofilament Contraction in Human Heart Failure. Insights From Electromechanical Simulations

摘要

Intracellular Ca₂₊ is the main activator of myofilament contraction and the altered Ca₂₊ handling observed in failing cells has been established as the leading cause of reduced inotropy in heart failure. Electrophysiological studies usually quantify Ca₂₊ transients to estimate contractile effects. However, heart failure remodeling of myofilaments also occurs, modifying the correlation between Ca₂+ and force. The aim of this study was to analyze myofilament tension generated by action potentials in human heart failure. In a ventricular electromechanical we investigated cellular contraction force associated with intracellular Ca₂₊ in heart failure by implementing the characteristic electrophysiological,β-adrenergic, and mechanical changes. Despite the inotropic myofilament remodeling induced by heart failure, the maximal active tension in failing cells was one third of the force generated in normal cells. With isoproterenol,β-adrenergic stimulation increased systolic Ca₂₊, which enhanced myofilament tension by up to 150%, but failing cells also showed a smaller contraction force compared to normal. We observed that contractility was very sensitive to changes in intracellular Ca₂₊, confirming that increasing Ca₂₊ peak would improve contraction in heart failure.