Mitochondrial Dysfunction: A New Frontier in the Search for Elusive Arrhythmia Mechanisms

A commentary on The role of mitochondria for the regulation of cardiac alternans. by Florea, S. M., and Blatter, L. A. (2010). Front. Physio. 1:141. doi:10.3389/fphys.2010.00141. Mitochondria have long been recognized for their importance in energy production and apoptosis. More recently, seminal work in various laboratories has extended the role of cardiac mitochondria from relatively static arbitrators of cell death and survival pathways to highly dynamic organelles that formed interactive networks across cardiomyocytes. These coupled networks were shown to strongly affect cardiomyocyte responses to oxidative stress by modulating key cell signaling pathways that strongly impacted physiological propertie

Cardiac I-1c Overexpression With Reengineered AAV Improves Cardiac Function in Swine Ischemic Heart Failure

Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 1013 vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 1012 vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure–volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF

Additional file 2 of Quantitative CT screening improved lumbar BMD evaluation in older patients compared to dual-energy X-ray absorptiometry

Additional file 2: Supplementary Table 2. Distribution of diagnostic category for lumbar BMD in male

Additional file 6 of Quantitative CT screening improved lumbar BMD evaluation in older patients compared to dual-energy X-ray absorptiometry

Additional file 6: Supplementary Figure 3. The residual-versus-fitted plot shows that fitted values do not have an obvious trend of failure

Additional file 1 of Quantitative CT screening improved lumbar BMD evaluation in older patients compared to dual-energy X-ray absorptiometry

Additional file 1: Supplementary Table 1. Distribution of diagnostic category for lumbar BMD in female