Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 μm. This allowed extensive analyses revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control versus infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale.
Neuroeconomics has the potential to fundamentally change the way economics is done. This article identifies the ways in which this will occur, pitfalls of this approach, and areas where progress has already been made. The value of neuroeconomics studies for social policy lies in the quality, replicability, and relevance of the research produced. While most economists will not contribute to the neuroeconomics literature, we contend that most economists should be reading these studies.
This work introduces a low-cost open-source electrocardiography (ECG) simulator comprising both MATLAB software for signal generation and a dedicated circuit board for signal output via a commercial sound card. Synthetic, rate-dependent ECG simulation is based on third-order polynomials that are calculated in sections for the main waves and spikes, respectively. Besides the heart rate, the output profile is fully adjustable with respect to Einthoven lead signals I-III, the amplitudes of the individual ECG waves and spikes, as well as the constitution and intensity of common distortions. The underlying coefficients for the synthetic ECG profile are obtained experimentally by analysing recordings of 22 healthy individuals with heart rates in the range of 40-180 bpm. Eight of these recordings are selected to determine the coefficients for the polynomials (training set) while the remaining 14 serve as test set to evaluate their applicability and accuracy. Thereby, a mean correlation of 98.57% is found which is superior in comparison with a widely accepted rate-dependent ECG profile that is generated from square root and linear terms (correlation score: 91.46%). Although other use-cases are feasible, the focus of this work is the development of an ECG simulator for academic research and university education. Both the MATLAB source code and the circuit layout files are available in the online supplement stimulating further work on this topic.
SummaryCells residing in the cardiac niche are constantly experiencing physical stimuli, including electrical pulses and cyclic mechanical stretch. These physical signals are known to influence a variety of cellular functions, including the secretion of growth factors and extracellular matrix proteins in cardiac fibroblasts, calcium handling and contractility in cardiomyocytes, or stretch-activated ion channels in muscle and non-muscle cells of the cardiovascular system. Recent progress in cardiac tissue engineering suggests that controlled physical stimulation can lead to functional improvements in multicellular cardiac tissue constructs. To study these effects, aspects of the physical environment of the myocardium have to be mimicked in vitro. This protocol demonstrates how a specifically designed bioreactor system allows controlled exposure of cultured cells, during continuous live imaging, to cyclic stretch, rhythmic electrical stimulation, fluid perfusion, at user-defined temperatures.
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