Altogether, this study has important impacts on AIP care underlying that hemin needs to be restricted to severe neurovisceral crisis and suggests that alternative treatment targeting the liver such as ALAS1 and HO1 inhibitors, and anti-inflammatory therapies should be considered in patients with recurrent AIP.

Pasqualin C, Gannier F, Yu A, Malécot CO, Bredeloux P, Maupoil V. SarcOptiM for ImageJ: high-frequency online sarcomere length computing on stimulated cardiomyocytes. Am J Physiol Cell Physiol 311: C277-C283, 2016. First published June 22, 2016; doi:10.1152/ajpcell.00094.2016.-Accurate measurement of cardiomyocyte contraction is a critical issue for scientists working on cardiac physiology and physiopathology of diseases implying contraction impairment. Cardiomyocytes contraction can be quantified by measuring sarcomere length, but few tools are available for this, and none is freely distributed. We developed a plug-in (SarcOptiM) for the ImageJ/Fiji image analysis platform developed by the National Institutes of Health. SarcOptiM computes sarcomere length via fast Fourier transform analysis of video frames captured or displayed in ImageJ and thus is not tied to a dedicated video camera. It can work in real time or offline, the latter overcoming rotating motion or displacement-related artifacts. SarcOptiM includes a simulator and video generator of cardiomyocyte contraction. Acquisition parameters, such as pixel size and camera frame rate, were tested with both experimental recordings of rat ventricular cardiomyocytes and synthetic videos. It is freely distributed, and its source code is available. It works under Windows, Mac, or Linux operating systems. The camera speed is the limiting factor, since the algorithm can compute online sarcomere shortening at frame rates Ͼ10 kHz. In conclusion, SarcOptiM is a free and validated user-friendly tool for studying cardiomyocyte contraction in all species, including human. cardiomyocyte contractility; sarcomere dynamic; video analysis; ImageJ plug-in; fast Fourier transform ISOLATED CARDIOMYOCYTE (CM) contractions can be recorded and measured with two main methods: cell shortening and sarcomere shortening. The latter is probably the most common and reliable technique used to characterize isolated CM contractile performance, because it does not depend on cell shape and size (4). Sarcomere shortening technique has applications in different research fields, including cardiovascular physiology, pathophysiology such as heart failure, pharmacology, and toxicology (2, 3, 6 -8, 11).Under transmission light microscopy, striated muscle cell sarcomeres show a transverse pattern due to the alternation of light (isotropic; I) and dark (anisotropic; A) bands, corresponding to the very regular organization of thin filaments of actin associated with regulatory proteins, such as tropomyosin and troponin (I band) and thick filaments of myosin (A band). These bands have a profile that can be assimilated to a sinusoidal curve. The frequency of this sinusoid, which represents the distance between the dark bands of the myosin filaments and, therefore, the sarcomere length (SL), can be extracted from Fourier spectrum analysis of the CM image.

Mechanisms underlying ectopic activity in the pulmonary vein (PV) which triggers paroxysmal atrial fibrillation are unknown. Although several studies have suggested that calcium signalling might be involved in these arrhythmias, little is known about calcium cycling in PV cardiomyocytes (CM). We found that individual PV CM showed a wide range of transverse tubular incidence and organization, going from their virtual absence, as described in atrial CM, to well transversally organised tubular systems, like in ventricular CM. These different types of CM were found in groups scattered throughout the tissue. The variability of the tubular system was associated with cell to cell heterogeneity of calcium channel (Cav1.2) localisation and, thereby, of Cav1.2-Ryanodine receptor coupling. This was responsible for multiple forms of PV CM calcium transient. Spontaneous calcium sparks and waves were not only more abundant in PV CM than in LA CM but also associated with a higher depolarising current. In conclusion, compared with either the atrium or the ventricle, PV myocardium presents marked structural and functional heterogeneity.

Introduction and objective: Nowadays, investigations of heart physiology and pathophysiology rely more and more upon image analysis, whether for the detection and characterization of events in single cells or for the mapping of events and their characteristics across an entire tissue. These investigations require extensive skills in image analysis and/or expensive software, and their reproducibility may be a concern. Our objective was to build a robust, reliable and open-source software tool to quantify excitation–contraction related experimental data at multiple scales, from single isolated cells to the whole heart. Methods and results: A free and open-source ImageJ plugin, Spiky, was developed to detect and analyze peaks in experimental data streams. It allows rapid and easy analysis of action potentials, intracellular calcium transient and contraction data from cardiac research experiments. As shown in the provided examples, both classical bi-dimensional data (XT signals) and video data obtained from confocal microscopy and optical mapping experiments (XYT signals) can be analyzed. Spiky was written in ImageJ Macro Language and JAVA, and works under Windows, Mac and Linux operating systems. Conclusion: Spiky provides a complete working interface to process and analyze cardiac physiology research data.

Supplementary data are available at Bioinformatics online.