Mitochondrial structure and function are not different between nonfailing donor and end-stage failing human hearts.

During human heart failure, the balance of cardiac energy use switches from predominantly fatty acids (FAs) to glucose. We hypothesized that this substrate shift was the result of mitochondrial degeneration; therefore, we examined mitochondrial oxidation and ultrastructure in the failing human heart by using respirometry, transmission electron microscopy, and gene expression studies of demographically matched donor and failing human heart left ventricular (LV) tissues. Surprisingly, respiratory capacities for failing LV isolated mitochondria (n = 9) were not significantly diminished compared with donor LV isolated mitochondria (n = 7) for glycolysis (pyruvate + malate)- or FA (palmitoylcarnitine)-derived substrates, and mitochondrial densities, assessed via citrate synthase activity, were consistent between groups.

Diet-induced obesity promotes altered remodeling and exacerbated cardiac hypertrophy following pressure overload.

Heart failure (HF) is the end stage of cardiovascular disease, in which hypertrophic remodeling no longer meets cardiac output demand. Established animal models of HF have provided insights into disease pathogenesis. However, these models are developed on dissimilar metabolic backgrounds from humans - patients with HF are frequently overweight or obese, whereas animal models of HF are typically lean.

Reduced response to IKr blockade and altered hERG1a/1b stoichiometry in human heart failure.

Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and action potential (AP) prolongation are hallmark proarrhythmic changes in the failing myocardium, which potentially result from alterations in repolarizing potassium currents. Thus, we aimed to examine whether decreased expression of the rapid delayed rectifier potassium current, IKr, contributes to repolarization abnormalities in human HF.

Human cardiac systems electrophysiology and arrhythmogenesis: iteration of experiment and computation.

Human cardiac electrophysiology (EP) is a unique system for computational modelling at multiple scales. Due to the complexity of the cardiac excitation sequence, coordinated activity must occur from the single channel to the entire myocardial syncytium. Thus, sophisticated computational algorithms have been developed to investigate cardiac EP at the level of ion channels, cardiomyocytes, multicellular tissues, and the whole heart.