Unlabelled: Stroke is a leading cause of death and disability worldwide. Atrial myopathy, including fibrosis, is associated with an increased risk of ischemic stroke, but the mechanisms underlying this association are poorly understood. Fibrosis modifies myocardial structure, impairing electrical propagation and tissue biomechanics, and creating stagnant flow regions where clots could form.
View Article and Find Full Text PDFExpert Rev Cardiovasc Ther
December 2023
Introduction: Atrial fibrillation (AF) is an increasingly prevalent and significant worldwide health problem. Manifested as an irregular atrial electrophysiological activation, it is associated with many serious health complications. AF affects the biomechanical function of the heart as contraction follows the electrical activation, subsequently leading to reduced blood flow.
View Article and Find Full Text PDFCardiomyocytes are the functional building blocks of the heart-yet most models developed to simulate cardiac mechanics do not represent the individual cells and their surrounding matrix. Instead, they work on a homogenized tissue level, assuming that cellular and subcellular structures and processes scale uniformly. Here we present a mathematical and numerical framework for exploring tissue-level cardiac mechanics on a microscale given an explicit three-dimensional geometrical representation of cells embedded in a matrix.
View Article and Find Full Text PDFThe immature physiology of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) limits their utility for drug screening and disease modelling. Here we show that suitable combinations of mechanical stimuli and metabolic cues can enhance the maturation of hiPSC-derived cardiomyocytes, and that the maturation-inducing cues have phenotype-dependent effects on the cells' action-potential morphology and calcium handling. By using microfluidic chips that enhanced the alignment and extracellular-matrix production of cardiac microtissues derived from genetically distinct sources of hiPSC-derived cardiomyocytes, we identified fatty-acid-enriched maturation media that improved the cells' mitochondrial structure and calcium handling, and observed divergent cell-source-dependent effects on action-potential duration (APD).
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