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Artificial intelligence algorithms are being adopted to analyze medical data, promising faster interpretation to support doctors' diagnostics. The next frontier is to bring these powerful algorithms to implantable medical devices. Herein, a closed-loop solution is proposed, where a cellular neural network is used to detect abnormal wavefronts and wavebrakes in cardiac signals recorded in human tissue is trained to achieve96% accuracy,92% precision,99% specificity, and93% sensitivity, when floating point precision weights are assumed. Unfortunately, the current hardware technologies for floating point precision are too bulky or energy intensive for compact standalone applications in medical implants. Emerging device technologies, such as memristors, can provide the compact and energy-efficient hardware fabric to support these efforts and can be reliably embedded with existing sensor and actuator platforms in implantable devices. A distributed design that considers the hardware limitations in terms of overhead and limited bit precision is also discussed. The proposed distributed solution can be easily adapted to other medical technologies that require compact and efficient computing, like wearable devices and lab-on-chip platforms.

Background: Epicardial adipose tissue (EAT) accumulation is associated with cardiac arrhythmias. The effect of EAT secretome (EATs) on cardiac electrophysiology remains largely unknown. Objective: The purpose of this study was to investigate the arrhythmogenicity of EATs and its underlying molecular and electrophysiological mechanisms. Methods: We collected atrial EAT and subcutaneous adipose tissue (SAT) from 30 patients with atrial fibrillation (AF), and EAT from 3 donors without AF. The secretome was collected after a 24-hour incubation of the adipose tissue explants. We cultured neonatal rat ventricular myocytes (NRVMs) with EATs, subcutaneous adipose tissue secretome (SATs), and cardiomyocytes conditioned medium (CCM) for 72 hours. We implemented the electrophysiological changes observed after EATs incubation into a model of human left atrium and tested arrhythmia inducibility. Results: Incubation of NRVMs with EATs decreased expression of the potassium channel subunit Kcnj2 by 26% and correspondingly reduced the inward rectifier K+ current IK1 by 35% compared to incubation with CCM, resulting in a depolarized resting membrane of cardiomyocytes. EATs decreased expression of connexin43 (29% mRNA, 46% protein) in comparison to CCM. Cells incubated with SATs showed no significant differences in Kcnj2 or Gja1 expression in comparison to CCM, and their resting potential was not depolarized. Cardiomyocytes incubated with EATs showed reduced conduction velocity and increased conduction heterogeneity compared to SATs and CCM. Computer modeling of human left atrium revealed that the electrophysiological changes induced by EATs promote sustained reentrant arrhythmias if EAT partially covers the myocardium. Conclusion: EAT slows conduction, depolarizes the resting potential, alters electrical cell–cell coupling, and facilitates reentrant arrhythmias.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic–tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans. A functional interfacial material has been developed for soft integration of bioelectronic devices with biological tissues. This has been applied in battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy as well as wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays.

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

Background: Right ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT’s unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT. Methods: We conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics. Results: We found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions ( P =0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions ( P =0.034) and partially reversed action potential duration at 80% repolarization shortening ( P =0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium ( P =0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT. Conclusions: Human RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.

The rigidity and relatively primitive modes of operation of catheters equipped with sensing or actuation elements impede their conformal contact with soft-tissue surfaces, limit the scope of their uses, lengthen surgical times and increase the need for advanced surgical skills. Here, we report materials, device designs and fabrication approaches for integrating advanced electronic functionality with catheters for minimally invasive forms of cardiac surgery. By using multiphysics modelling, plastic heart models and Langendorff animal and human hearts, we show that soft electronic arrays in multilayer configurations on endocardial balloon catheters can establish conformal contact with curved tissue surfaces, support high-density spatiotemporal mapping of temperature, pressure and electrophysiological parameters and allow for programmable electrical stimulation, radiofrequency ablation and irreversible electroporation. Integrating multimodal and multiplexing capabilities into minimally invasive surgical instruments may improve surgical performance and patient outcomes.

Defibrillation remains the only effective therapy against sudden cardiac death. However, the current coil-based lead ICD devices are limited by high defibrillation threshold (DFT) and low arrhythmia sensing resolution, which can result in inappropriate and painful shocks adversely affecting the quality of life. Emerging classes of materials and mechanics concepts in the field of flexible and stretchable electronics have created new opportunities for integrating high-performance electronics with the human body and its organs and various tissues. These conformal electronics devices offer a platform for high-definition arrhythmia sensing to minimize inappropriate shocks and improve therapy and high-definition therapy delivery circuit to reduce DFT.

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

We present a novel modification of genetic algorithm (GA) which determines personalized parameters of cardiomyocyte electrophysiology model based on set of experimental human action potential (AP) recorded at different heart rates. In order to find the steady state solution, the optimized algorithm performs simultaneous search in the parametric and slow variables spaces. We demonstrate that several GA modifications are required for effective convergence. Firstly, we used Cauchy mutation along a random direction in the parametric space. Secondly, relatively large number of elite organisms (6-10% of the population passed on to new generation) was required for effective convergence. Test runs with synthetic AP as input data indicate that algorithm error is low for high amplitude ionic currents (1.6±1.6% for IKr, 3.2±3.5% for IK1, 3.9±3.5% for INa, 8.2±6.3% for ICaL). Experimental signal-to-noise ratio above 28 dB was required for high quality GA performance. GA was validated against optical mapping recordings of human ventricular AP and mRNA expression profile of donor hearts. In particular, GA output parameters were rescaled proportionally to mRNA levels ratio between patients. We have demonstrated that mRNA-based models predict the AP waveform dependence on heart rate with high precision. The latter also provides a novel technique of model personalization that makes it possible to map gene expression profile to cardiac function.

Supplemental Digital Content is available in the text., Background: The mechanisms sustaining myocardial fibrillation remain disputed, partly due to a lack of mapping tools that can accurately identify the mechanism with low spatial resolution clinical recordings. Granger causality (GC) analysis, an econometric tool for quantifying causal relationships between complex time-series, was developed as a novel fibrillation mapping tool and adapted to low spatial resolution sequentially acquired data. Methods: Ventricular fibrillation (VF) optical mapping was performed in Langendorff-perfused Sprague-Dawley rat hearts (n=18), where novel algorithms were developed using GC-based analysis to (1) quantify causal dependence of neighboring signals and plot GC vectors, (2) quantify global organization with the causality pairing index, a measure of neighboring causal signal pairs, and (3) localize rotational drivers (RDs) by quantifying the circular interdependence of neighboring signals with the circular interdependence value. GC-based mapping tools were optimized for low spatial resolution from downsampled optical mapping data, validated against high-resolution phase analysis and further tested in previous VF optical mapping recordings of coronary perfused donor heart left ventricular wedge preparations (n=12), and adapted for sequentially acquired intracardiac electrograms during human persistent atrial fibrillation mapping (n=16). Results: Global VF organization quantified by causality pairing index showed a negative correlation at progressively lower resolutions (50% resolution: P=0.006, R2=0.38, 12.5% resolution, P=0.004, R2=0.41) with a phase analysis derived measure of disorganization, locations occupied by phase singularities. In organized VF with high causality pairing index values, GC vector mapping characterized dominant propagating patterns and localized stable RDs, with the circular interdependence value showing a significant difference in driver versus nondriver regions (0.91±0.05 versus 0.35±0.06, P=0.0002). These findings were further confirmed in human VF. In persistent atrial fibrillation, a positive correlation was found between the causality pairing index and presence of stable RDs (P=0.0005,R2=0.56). Fifty percent of patients had RDs, with a low incidence of 0.9±0.3 RDs per patient. Conclusions: GC-based fibrillation analysis can measure global fibrillation organization, characterize dominant propagating patterns, and map RDs using low spatial resolution sequentially acquired data.

Conformal electronics are stretchable, flexible electronic devices that can diagnose and treat tissue functions with high spatiotemporal resolution. These devices are comprised of a network of sensors and actuators, which include electrodes, photodiodes, thermocouples, LEDs, pressure transducers, and photovoltaic devices. Conformal electronics can conform to the epicardium or endocardium to multiparametrically monitor and correct cardiac tissue function. Currently in the clinic, many catheter-based technologies and implantable mechanical and electrotherapeutic devices are employed for the diagnosis and treatment of cardiac arrhythmias and heart failure. Conformal electronics offers improved systems for the monitoring and delivery of therapy for cardiac diseases, including piezoelectric energy harvesting and storage systems, 3D multifunctional integumentary membranes, multifunctional balloon catheters, ultrathin injectable multimodal sensors, capacitively-coupled flexible sensing systems, and soft robotic sleeves for mechanical support. Conformal electronics will enable a new generation of devices to transform the current paradigm of cardiac diagnosis and therapy.

Background Computational models of myocardial ischemia often use oversimplified ischemic source representations to simulate epicardial potentials. The purpose of this study was to explore the influence of biophysically justified, subject-specific ischemic zone representations on epicardial potentials. Methods We developed and implemented an image-based simulation pipeline, using intramural recordings from a canine experimental model to define subject-specific ischemic regions within the heart. Static epicardial potential distributions, reflective of ST segment deviations, were simulated and validated against measured epicardial recordings. Results Simulated epicardial potential distributions showed strong statistical correlation and visual agreement with measured epicardial potentials. Additionally, we identified and described in what way border zone parameters influence epicardial potential distributions during the ST segment. Conclusion From image-based simulations of myocardial ischemia, we generated subject-specific ischemic sources that accurately replicated epicardial potential distributions. Such models are essential in understanding the underlying mechanisms of the bioelectric fields that arise during ischemia and are the basis for more sophisticated simulations of body surface ECGs.

We present a novel genetic algorithm-based solution to determine the set of cardiomyocyte model parameters based on experimental human action potential (AP) recordings. The novel approach is based on AP waveform dependence on the heart rate. In order to find the steady-state solution, optimized parameters include conductivities of ionic channels and exchangers augmented by slow variables, intracellular sodium concentration and sarcoplasmic reticulum calcium load. The algorithm is enhanced by a novel mutation operator, based on Cauchy distribution along a random direction in parameter space. We also demonstrate that increasing the number of elite organisms up to 7% results in faster convergence. Test runs indicate that algorithm error is below 5% for IKr, 7% for IK1 and INa and 13% for ICaL. Experimental signal-to-noise ratio above 28 dB was sufficient for high quality algorithm performance. The algorithm validation using optical mapping recordings of human ventricular AP demonstrated low error that was below 6 mV for AP waveform and less than 16 ms for AP duration. Further validation of the personalized models was done using mRNA expression profile of two donor hearts. The mRNA-based model reproduced AP waveform dependence on cycle length with 13 mV accuracy and AP duration with 20 ms accuracy.

Background We previously developed a computational model to aid clinicians in positioning implantable cardioverter-defibrillators (ICDs), especially in the case of abnormal anatomies that commonly arise in pediatric cases. We have validated the model clinically on the body surface; however, validation within the volume of the heart is required to establish complete confidence in the model and improve its use in clinical settings. Objective The goal of this study was to use an animal model and thoracic phantom to record the ICD potential field within the heart and on the torso to validate our defibrillation simulation system. Methods We recorded defibrillator shock potentials from an ICD suspended together with an animal heart in a human-shaped torso tank and compared them with simulated values. We also compared the scaled distribution threshold, an analog to the defibrillation threshold, calculated from the measured and simulated electric fields within the myocardium. Results ICD potentials recorded on the tank and cardiac surface and within the myocardium agreed well with those predicted by the simulation. A quantitative comparison of the recorded and simulated potentials yielded a mean correlation of 0.94 and a relative error of 19.1%. The simulation can also predict scaled distribution thresholds similar to those calculated from the measured potential fields. Conclusion We found that our simulation could predict potential fields with high correlation with the measured values within the heart and on the torso surface. These results support the use of this model for the optimization of ICD placements.

Background: Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death because of ventricular fibrillation (VF). Consequently, Food and Drug Administration recommends testing all pharmacological agents for QT toxicity as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in cardiac tissue conductivity. Mines demonstrated in 1913 that cardiac wavelength (λ) determines inducibility of reentrant arrhythmia, where both repolarization time or action potential duration and conduction velocity determine λ=action potential duration×conduction velocity. We aimed to determine the role of anisotropic wavelength in inducibility of VF in explanted human left ventricular preparations. We tested the hypothesis that 3-dimensional cardiac wavelength, which takes into account anisotropic cardiac tissue conductivity, can accurately predict VF sustainability. Methods: We conducted panoramic optical mapping of coronary perfused human left ventricular wedge preparations subjected to pharmacologically induced shortening and prolongation of action potential duration, by I K,ATP agonist pinacidil and antagonist glybenclamide, respectively. This measured action potential duration, conduction velocity, and thus determined pacing cycle length–dependent wavelengths in longitudinal (λ L ), transverse (λ TV ), and transmural (λ TM ) directions using S1S1 pacing protocol, from which wavelength volume (V λ ) was determined, as V λ =λ L ×λ TV ×λ TM , and compared with tissue volume . We tested a hypothesis that tissue volume/V λ ratio can predict VF sustainability. Results: At baseline, at pacing rate of 240 beats per minute, the wavelengths were λ L =9.6±0.6 cm, λ TV =4.2±0.3 cm, and λ TM =5.8±0.2 cm, respectively (n=7), and thus V λ =246.4±42.1 cm 3 . Administration of pinacidil at escalating concentrations progressively decreased V λ , and VF became sustained, when tissue volume/V λ was above safety factor κ=4.4±0.6 (n=9) during rapid pacing. Treatment with glybenclamide decreased V T /V λ below κ at any pacing rate and prevented VF sustainability. Conclusions: Sustained VF was only sustained in ventricular volume exceeding critical V λ =λ L ×λ TV ×λ TM .

[This corrects the article DOI: 10.1371/journal.pone.0231695.].

Heart failure (HF) is a major cause of morbidity and mortality worldwide. The global burden of HF continues to rise, with prevalence rates estimated at 1-2% and incidence approaching 5-10 per 1000 persons annually. The complex pathophysiology of HF impacts virtually all aspects of normal cardiac function - from structure and mechanics to metabolism and electrophysiology - leading to impaired mechanical contraction and sudden cardiac death. Pharmacotherapy and device therapy are the primary methods of treating HF, but neither is able to stop or reverse disease progression. Thus, there is an acute need to translate basic research into improved HF therapy. Animal model investigations are a critical component of HF research. However, the translation from cellular and animal models to the bedside is hampered by significant differences between species and among physiological scales. Our studies over the last 8 years show that hypotheses generated in animal models need to be validated in human in vitro models. Importantly, however, human heart investigations can establish translational platforms for safety and efficacy studies before embarking on costly and risky clinical trials. This review summarizes recent developments in human HF investigations of electrophysiology remodelling, metabolic remodelling, and β-adrenergic remodelling and discusses promising new technologies for HF research.

Fluorescence optical imaging techniques have revolutionized the field of cardiac electrophysiology and advanced our understanding of complex electrical activities such as arrhythmias. However, traditional monocular optical mapping systems, despite having high spatial resolution, are restricted to a two-dimensional (2D) field of view. Consequently, tracking complex three-dimensional (3D) electrical waves such as during ventricular fibrillation is challenging as the waves rapidly move in and out of the field of view. This problem has been solved by panoramic imaging which uses multiple cameras to measure the electrical activity from the entire epicardial surface. However, the diverse engineering skill set and substantial resource cost required to design and implement this solution have made it largely inaccessible to the biomedical research community at large. To address this barrier to entry, we present an open source toolkit for building panoramic optical mapping systems which includes the 3D printing of perfusion and imaging hardware, as well as software for data processing and analysis. In this paper, we describe the toolkit and demonstrate it on different mammalian hearts: mouse, rat, and rabbit.

See Article by Panitchob et al > As to the fundamental mechanisms of fibrillation we have plenty of theories, but none is universally accepted… we may note in passing that they all center around two ideas … (a) that the impulses arise from centers or pacemakers, or (b) that the condition is caused by re-entry of impulses and the formation of circles of excitation. Each of these views, again, has two groups of exponents … (a) those who believe that a single focus, or excitation ring, occurs, and (b) those who favor the idea that multiple foci, or numerous circus rings, are developed. > > —Carl J. Wiggers, 19401 Ventricular fibrillation (VF) was likely recognized as early as 3500 BCE when the Ebers Papyrus2 described key features of fibrillation as follows: > “If the heart trembles, has little power and sinks, the disease is advancing and death is near.” The modern scientific effort to understand fibrillation did not begin until 1543, when Vesalius3 described worm-like movements in animal hearts during dissection just before they died. Erichsen4 in 1842 documented tumultuous, tremulous, and irregular behavior of ventricles consequent to coronary ligation. Hoffa and Ludwig5 first recorded VF using a kymograph (mechanical wave recorder) in 1850 (Figure, left). Interestingly, Hoffa, who was Ludwig’s pupil at the time, meant to stimulate neurons but accidentally stimulated the myocardium. They showed that irregular contractions of the ventricles could be induced by faradization (electric stimulation) and resulted in cardiac arrest that could not be checked by vagal stimulation. These studies of autonomic control of the heart suggested a neurogenic VF mechanism. Figure. The first recordings of ventricular fibrillation were acquired by Hoffa and Ludwig using a …

Myocardial ischemia is the response of the heart to reduced coronary blood flow, leading to changes in ST segment potentials. ST segment depression is regarded as an indicator of nontransmural myocardial ischemia; however, not all nontransmural ischemia results in ST depression. This apparent discrepancy may be the result of many complex factors in cardiac response mechanisms to reduced blood flow. As a result, sophisticated computer models have emerged that have provided key insights into this complex phenomenon and the circumstances surrounding ST depression. Though these models have been able to produce ST depressions, many have neglected the effect of intracavitary blood volume, associated with different phases of the cardiac cycle. To explore the influence of the cardiac blood volume variability on epicardial potentials during nontransmural ischemia, we incorporated a thin, subendocardial ischemic zone geometry into an anatomically realistic, image-based ventricular model, and generated a finite element, static bidomain solution to determine the resulting epicardial surface potentials. It was first determined that, under baseline conditions (i.e., expanded left ventricular volumes corresponding to diastole), a predictable ST depression developed over the ischemic region. Left ventricular volume was then incrementally reduced, while maintaining the size and general shape of the is-chemic region, in order to reflect the systolic phase of the cardiac cycle. As blood volume geometries decreased, epicardial ST depression overlying the ischemic region first increased in surface area as blood volume was reduced and before dramatically reducing near 30% blood volume reduction — accentuating the role and importance of blood volume variation in computational models ofischemia.

Introduction Myocardial ischemia is a pathological condition initiated by supply and demand imbalance of the blood to the heart. Previous studies suggest that ischemia originates in the subendocardium, i.e., that nontransmural ischemia is limited to the subendocardium. By contrast, we hypothesized that acute myocardial ischemia is not limited to the subendocardium and sought to document its spatial distribution in an animal preparation. The goal of these experiments was to investigate the spatial organization of ischemia and its relationship to the resulting shifts in ST segment potentials during short episodes of acute ischemia. Methods We conducted acute ischemia studies in open-chest canines (N = 19) and swines (N = 10), which entailed creating carefully controlled ischemia using demand, supply or complete occlusion ischemia protocols and recording intramyocardial and epicardial potentials. Elevation of the potentials at 40% of the ST segment between the J-point and the peak of the T-wave (ST40%) provided the metric for local ischemia. The threshold for ischemic ST segment elevations was defined as two standard deviations away from the baseline values. Results The relative frequency of occurrence of acute ischemia was higher in the subendocardium (78% for canines and 94% for swines) and the mid-wall (87% for canines and 97% for swines) in comparison with the subepicardium (30% for canines and 22% for swines). In addition, acute ischemia was seen arising throughout the myocardium (distributed pattern) in 87% of the canine and 94% of the swine episodes. Alternately, acute ischemia was seen originating only in the subendocardium (subendocardial pattern) in 13% of the canine episodes and 6% of the swine episodes (p Conclusions Our findings suggest that the spatial distribution of acute ischemia is a complex phenomenon arising throughout the myocardial wall and is not limited to the subendocardium.

Item does not contain fulltext INTRODUCTION: The "Experimental Data and Geometric Analysis Repository", or EDGAR is an Internet-based archive of curated data that are freely distributed to the international research community for the application and validation of electrocardiographic imaging (ECGI) techniques. The EDGAR project is a collaborative effort by the Consortium for ECG Imaging (CEI, ecg-imaging.org), and focused on two specific aims. One aim is to host an online repository that provides access to a wide spectrum of data, and the second aim is to provide a standard information format for the exchange of these diverse datasets. METHODS: The EDGAR system is composed of two interrelated components: 1) a metadata model, which includes a set of descriptive parameters and information, time signals from both the cardiac source and body-surface, and extensive geometric information, including images, geometric models, and measure locations used during the data acquisition/generation; and 2) a web interface. This web interface provides efficient, search, browsing, and retrieval of data from the repository. RESULTS: An aggregation of experimental, clinical and simulation data from various centers is being made available through the EDGAR project including experimental data from animal studies provided by the University of Utah (USA), clinical data from multiple human subjects provided by the Charles University Hospital (Czech Republic), and computer simulation data provided by the Karlsruhe Institute of Technology (Germany). CONCLUSIONS: It is our hope that EDGAR will serve as a communal forum for sharing and distribution of cardiac electrophysiology data and geometric models for use in ECGI research.

Introduction We hypothesize that electrocardiographic measurements from the intramyocardial space contain more sensitive markers of ischemia than those detectable on the epicardium. The goal of this study was to evaluate different electrical markers for their potential to detect the earliest phases of acute myocardial ischemia. Methods We conducted acute ischemia studies in open chest animal, by creating finely controlled demand or supply ischemic episodes and recording intramyocardial and epicardial potentials. Results Under the conditions of mild perfusion deficit, acute ischemia induced changes in the T wave that were larger and could be detected earlier on the epicardial surface than ST-segment changes. Conclusions Our findings indicate that in the setting of very acute ischemia, epicardial T waves have higher sensitivity to mild degrees of acute ischemia than epicardial ST potentials. These results suggest that changes in the T wave shape may augment shifts in ST segments to improve ECG based localization of ischemia.

Current computational models of acute ischemia are deficient because of their inability to be validated against experimental data and their lack of geometric realism. Past models of ischemia have been based on geometric primitives or hearts for which no electrical measurements exist. One consequence is that it is necessary to make modeling assumptions that are not supported by measurements or direct validation with experiments. Based on our subject specific simulations and measurements, we hypothesize that assumptions about the nature and scale of the border zone play a significant role in determining the cardiac potential distributions from ischemic sources of injury current. Geometrically accurate models were created from Magnetic Resonance Imaging (MRI) and Diffuser Tensor Imaging (DTI) after an in situ canine ischemia experiment. The ischemic zone was defined based on transmural electrode readings and was used in a static bidomain simulation representing a time point during the ST segment. Varying the width of the border zone in the simulations changed the magnitude and distribution of epicardial depressions and elevations. We also found that a border zone with linear variation of potential from healthy to ischemic regions was not adequate to simulate measured potentials. A more sophisticated border zone that included an explicit region of partial ischemia was necessary to simulate the field gradients seen in experimental data.

Introduction: Myocardial ischemia is a pathological condition initiated by supply and demand imbalance of the blood to the heart. Electrocardiographic ST-segment shifts are often used as markers for ischemia. Literature suggests that the progression of ischemia occurs from the endocardium, which has the highest metabolic demand, and spreads toward the epicardium, eventually becoming transmural. Our study with animal models has found the progression of ischemia to be more complex and heterogeneous in its distribution. Methods: We used in situ canine preparation, wherein the animals were subjected to demand ischemia by reducing coronary flow and increasing the heart rate through atrial pacing. Epicardial and transmural electrograms were recorded using a 247-electrode sock and up to 400 transmural needle electrodes. Results: At reduced coronary flow, increasing heart rates caused pockets of ischemic regions, characterized by ST-potential elevations to appear variously distributed in the epicardial, midmyocardial, and subendocardial regions. Further reduction in coronary flow and simultaneously increasing the heart rates increased the extent and the magnitude of the ischemic regions that eventually became transmural. Conclusion: The electrographic response of the heart to myocardial ischemia, contrary to earlier belief, is a much more complex phenomenon characterized by heterogeneous distribution and progression of ischemic regions.