Spread Of Electrical Activity Research Articles

Effect of Carvacrol, TRP Channels Modulator, on Cardiac Electrical Activity.

Despite the wide application of carvacrol (CAR) in medicines, dietary supplements, and foods, there is still insufficient electrophysiological data on the mechanisms of action of CAR, particularly with regard to heart function. Therefore, in this study, we attempted to elucidate whether CAR, whose inhibitory effect on both cardiac and vascular TRPM7 and L-type Ca2+ currents has been demonstrated previously, could modify cardiac electrical activity. We used a combination of optical mapping and microelectrode techniques to track the action potentials (APs) and the spread of electrical activity in a Langendorff-perfused rabbit heart model during atrial/endo/epicardial pacing. Simultaneously, ECG recordings were acquired. Because human trials on CAR are still lacking, we tested the action of CAR on human ventricular preparations obtained from explanted hearts. Activation time (AT), AP duration (APD), and conduction velocity maps were constructed. We demonstrated that at a low concentration (10 μM) of CAR, only marginal changes in the AP parameters were observed. At higher concentrations (≥100 μM), a decrease in AP upstroke velocity (dV/dtmax), suggesting inhibition of Na+ current, and APD (at 50 and 90% repolarization) was detected; also slowing in the spread of electrical signals via the atrioventricular node was observed, suggesting impaired functioning of Ca2+ channels. In addition, a decrease in the T-wave amplitude was seen on the ECG, suggesting an impaired repolarization process. Nevertheless, those changes occurred without a significant impact on the resting membrane potential and were reversible. We suggest that CAR might play a role in modulating cardiac electrical activity at high concentrations.

Double challenge: cochlear implantation in the only hearing ear with progressive hearing loss following meningitis and vestibular dysfunction after implantation

ObjectiveVestibular dysfunction associated with cochlear implantation is rare. It is usually seen in patients with otosclerosis due to spread of electrical activity throughout the demineralized bone. A 17-year old female with progressive hearing loss 2 years after meningitis and vestibular dysfunction in the implanted ear is presented in this study. FindingsThe patient had mild hearing loss in the right ear and total hearing loss on the left side because of complete ossification of the cochlea following meningitis. She had to have cochlear implantation in the right ear because of progression of hearing loss. She had successful implantation but she experienced vestibular dysfunction following activation of cochlear electrodes. Closure of two electrodes caused disruption of auditory programming. Then the patient was subjected to long term vestibular rehabilitation program. ConclusionTiming for implantation before the completion of cochlear ossification is crucial not to miss the chance for hearing restoration. However, difficulties in hearing rehabilitation due to extensive ossification can be doubled by vestibular problems triggered by stimulation of the vestibular nerve by cochlear electrodes. Attempts to reduce the balance problem will complicate auditory programming. Vestibular rehabilitation for long term helps to carry on hearing progress.

Cardiac intramural electrical mapping reveals focal delays but no conduction velocity slowing in the peri-infarct region.

Altered electrical behavior alongside healed myocardial infarcts (MIs) is associated with increased risk of sudden cardiac death. However, the multidimensional mechanisms are poorly understood and described. This study characterizes, for the first time, the intramural spread of electrical activation in the peri-infarct region of chronic reperfusion MIs. Four sheep were studied 13 wk after antero-apical reperfusion infarction. Extracellular potentials (ECPs) were recorded in a ~20 × 20-mm2 region adjacent to the infarct boundary (25 plunge needles <0.5-mm diameter with 15 electrodes at 1-mm centers) during multisite stimulation. Infarct geometry and electrode locations were reconstructed from magnetic resonance images. Three-dimensional activation spread was characterized by local activation times and interpolated ECP fields (n = 191 records). Control data were acquired in 4 non-infarcted sheep (n = 96 records). Electrodes were distributed uniformly around 15 ± 5% of the intramural infarct boundary. There were marked changes in pacing success and ECP morphology across a functional border zone (BZ) ±2 mm from the boundary. Stimulation adjacent to the infarct boundary was associated with low-amplitude electrical activity within the BZ and delayed activation of surrounding myocardium. Bulk tissue depolarization occurred 3.5-14.6 mm from the pacing site for 39% of stimuli with delays of 4-37 ms, both significantly greater than control (P < 0.0001). Conduction velocity (CV) adjacent to the infarct was not reduced compared with control, consistent with structure-only computer model results. Insignificant CV slowing, irregular stimulus-site specific activation delays, and obvious indirect activation pathways strongly suggest that the substrate for conduction abnormalities in chronic MI is predominantly structural in nature.NEW & NOTEWORTHY Intramural in vivo measurements of peri-infarct electrical activity were not available before this study. We use pace-mapping in a three-dimensional electrode array to show that a subset of stimuli in the peri-infarct region initiates coordinated myocardial activation some distance from the stimulus site with substantial associated time delays. This is site dependent and heterogeneous and occurs for <50% of ectopic stimuli in the border zone. Furthermore, once coordinated activation is initiated, conduction velocity adjacent to the infarct boundary is not significantly different from control. These results give new insights to peri-infarct electrical activity and do not support the widespread view of uniform electrical remodeling in the border zone of chronic myocardial infarcts, with depressed conduction velocity throughout.

The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse Retina

Background/Aims: Retinal prostheses use electrical stimulation to restore functional vision to patients blinded by retinitis pigmentosa. A key detail is the spatial pattern of ganglion cells activated by stimulation. Therefore, we characterized the spatial extent of network-mediated electrical activation of retinal ganglion cells (RGCs) in the epiretinal monopolar electrode configuration. Methods: Healthy mouse RGC activities were recorded with a micro-electrode array (MEA). The stimuli consisted of monophasic rectangular cathodic voltage pulses and cycling full-field light flashes. Results: Voltage tuning curves exhibited significant hysteresis, reflecting adaptation to electrical stimulation on the time scale of seconds. Responses decreased from 0 to 300 µm, and were also dependent on the strength of stimulation. Applying the Rayleigh criterion to the half-width at half-maximum of the electrical point spread function suggests a visual acuity limit of no better than 20/946. Threshold voltage showed only a modest increase across these distances. Conclusion: The existence of significant hysteresis requires that future investigations of electrical retinal stimulation control for such long-memory adaptation. The spread of electrical activation beyond 200 µm suggests that neighbouring electrodes in epiretinal implants based on indirect stimulation of RGCs may be indiscriminable at interelectrode spacings as large as 400 µm.

GELASTIC SEIZURES: NO LAUGHING MATTER

Introduction Gelastic seizures are usually the first manifestation of hypothalamic hamartomas. Progression to intractable epilepsy with multiple seizure types occurs. Typical temporal lobe seizures with corresponding temporal lobe electrographic changes occur and represent spread of electrical activity from the hypothalamic hamartoma to the cortex. Such patients have undergone temporal lobectomy with no clinical improvement. The only curative management is removal of the hamartoma. Case A 30 year old lady with gelastic seizures since age 12 progressed to have simple and complex partial seizures that were drug refractory. She had multiple MRIs reported as normal and underwent vagal nerve stimulator insertion in 2007 with limited benefit. Video telemetry, positron emission tomography-computed tomography (PET-CT) and subdural electrode recording were supportive of the right temporal lobe being the source. She underwent right temporal lobectomy with hippocampectomy with hippocampal sclerosis on histology. She re-attended six weeks post-operatively with seizure recurrence. Repeat MRI revealed a right hypothalamic hamartoma, which on re-review was present on her 2010 MRI. Her seizure frequency continues to increase and she is awaiting consideration of further surgical intervention. Conclusion Gelastic seizures although rare should prompt investigation for a hypothalamic hamartoma. Surgical intervention is the key to curative management.

Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

Initiation of Ventricular Fibrillation by a Single Ectopic Beat in Three Dimensional Numerical Models of Ischemic Heart Disease: Abrupt Transition to Chaos

Background: To explore the conditions most dangerous for the emergence of sustained Ventricular Tachycardia or Ventricular Fibrillation (VT/VF) a new computational model of ventricular myocardium including 2592 finite elements in three dimensions was created. Methods: The fully three dimensional model of right and left ventricular muscle was used to simulate the spread of electrical activation and the resulting electrocardiogram. Localized zones of ischemic muscle tissue were characterized by reduced conduction velocity and reduced refractory period, and VT/VF was initiated by single ectopic beats. The simulated body surface Electrocardiogram (ECG) was also computed. Results: In this system clinically realistic VT/VF is readily produced by single stimuli. Reduced conduction velocity and reduced effective refractory period in localized abnormal muscle predispose to VT/VF. Transition to chaos was abrupt. No one specific pattern of re-entry, spiral waves, or vortices could be identified that later decomposed into VT/VF. Instead, there was a wide variety of activation patterns leading to chaos, depending sensitively on initial conditions. Nonetheless, a clear border between stable vs. chaotic behavior was defined by a critical threshold impulse wavelength, the product of conduction velocity and refractory period, γ*, in local ischemic tissue. This threshold, separating stable and chaotic regimes, can be specified precisely as γ*=FV1/3 , where V is the local volume of diseased tissue and 0 γ F γ 1 is a shape factor, near 1 for compact volumes and progressively smaller for flattened volumes. When the impulse wavelength is ≤γ*, VT/VF happens. Typical values for γ* range from 1 to 3 cm. Such behavior is characteristic of classical chaotic systems. Conclusions: The patterns of muscle activation leading to self-sustaining VT/VF observed in three dimensional diseased hearts are much more complex and variable than traditional re-entry in two dimensions. Instead a model of abrupt transition to chaos emerges from the application of first-principles cardiac electrophysiology, realistic ventricular anatomy, and the pathophysiology of ischemic cardiac muscle. This phenomenon may represent a higher order form of mathematical chaos than has been previously studied.

Introduction to the Series on Computational Approaches to Cardiac Arrhythmias

Of all the cardiac arrhythmias seen in clinical practice, atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are among the leading causes of morbidity and mortality in the developed world. AF is the most common sustained arrhythmia and is associated with an increased risk of stroke, heart failure, dementia, and death.1–3 In developed nations overall prevalence of AF is 0.9% and the number of people affected is projected to more than double over the next 2 decades.3,4 VT/VF is the most important immediate cause of sudden cardiac death (SCD). Incidence of SCD is estimated to be 4 to 5 million cases per year worldwide.5,6 Thus arrhythmias and SCD are among the most significant manifestations of cardiovascular diseases worldwide, but their underlying mechanisms remain elusive. Arrhythmogenic substrates may be established by ischemia, infarction, heart failure and genetic mutations, all of which may cause inflammation, extracellular matrix remodeling, interstitial fibrosis, fatty infiltration, and changes in the 3-dimensional cellular architecture of the working myocardium.7,8 Over the last 17 years, the study of the molecular genetic basis of monogenic cardiac rhythm disorders, together with characterization of functional expression and biophysical properties of mutant channels from patients with inheritable ion channel diseases, has significantly advanced our understanding of the molecular basis of cardiac arrhythmias.9 Yet, this clearly has not been sufficient. Despite such advances, predictable prevention of AF or VF is currently not possible and the development of effective antiarrhythmic pharmacological agents has been extremely difficult. Not all questions related to arrhythmia mechanisms are directly answerable by reductionist experiments such as DNA sequencing or patch clamping. There is a hierarchy of questions whose levels are determined by the generality of the answers sought. Thus the question of what a mutation in an ion …

Optimizing Electrode Placement for Hemodynamic Benefit in Cardiac Resynchronization Therapy

Research is needed to explore the relative benefits of alternative electrode placements in biventricular and left ventricular (LV) pacing for heart failure with left bundle branch block (LBBB). A fast computational model of the left ventricle, running on an ordinary laptop computer, was created to simulate the spread of electrical activation over the myocardial surface, together with the resulting electrocardiogram, segmental wall motion, stroke volume, and ejection fraction in the presence of varying degrees of mitral regurgitation. Arbitrary zones of scar and blocked electrical conduction could be modeled. Simulations showed there are both sweet spots and poor spots for LV electrode placement, sometimes separated by only a few centimeters. In heart failure with LBBB, pacing at poor spots can produce little benefit or even reduce pumping effectiveness. Pacing at sweet spots can produce up to 35% improvement in ejection fraction. Relatively larger benefit occurs in dilated hearts, in keeping with the greater disparity between early and late activated muscle. Sweet spots are typically located on the basal to midlevel, inferolateral wall. Poor spots are located on or near the interventricular septum. Anteroapical scar with conduction block causes little shift in locations for optimal pacing. Hearts with increased passive ventricular compliance and absence of preejection mitral regurgitation exhibit greater therapeutic gain. The durations and wave shapes of QRS complexes in the electrocardiogram can help predict optimum electrode placement in real time. Differences between poor responders and hyperresponders to cardiac resynchronization therapy can be understood in terms of basic anatomy, physiology, and pathophysiology. Computational modeling suggests general strategies for optimal electrode placement. In a given patient heart size, regional pathology and regional dynamics allow individual pretreatment planning to target optimal electrode placement.

Use of endogenous NADH fluorescence for real-time in situ visualization of epicardial radiofrequency ablation lesions and gaps

Radiofrequency ablation (RFA) aims to produce lesions that interrupt reentrant circuits or block the spread of electrical activation from sites of abnormal activity. Today, there are limited means for real-time visualization of cardiac muscle tissue injury during RFA procedures. We hypothesized that the fluorescence of endogenous NADH could be used as a marker of cardiac muscle injury during epicardial RFA procedures. Studies were conducted in blood-free and blood-perfused hearts from healthy adult Sprague-Dawley rats and New Zealand rabbits. Radiofrequency was applied to the epicardial surface of the heart using a 4-mm standard blazer ablation catheter. A dual camera optical mapping system was used to monitor NADH fluorescence upon ultraviolet illumination of the epicardial surface and to record optical action potentials using the voltage-sensitive probe RH237. Epicardial lesions were seen as areas of low NADH fluorescence. The lesions appeared immediately after ablation and remained stable for several hours. Real-time monitoring of NADH fluorescence allowed visualization of viable tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical activity linked the gaps between lesions to postablation reentries. We found that the fluorescence of endogenous NADH aids the visualization of injured epicardial tissue caused by RFA. This was true for both blood-free and blood-perfused preparations. Gaps between NADH-negative regions revealed unablated tissue, which may promote postablation reentry or provide pathways for the conduction of abnormal electrical activity.

Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI

It has been shown by histology that cardiac myocytes are organized into laminae and this structure is important in function, both influencing the spread of electrical activation and enabling myocardial thickening in systole by laminar sliding. We have carried out high-spatial resolution three-dimensional MRI of the ventricular myolaminae of the entire volume of the isolated rat heart after contrast perfusion [dimeglumine gadopentate (Gd-DTPA)]. Four ex vivo rat hearts were perfused with Gd-DTPA and fixative and high-spatial resolution MRI was performed on a 9.4T MRI system. After MRI, cryosectioning followed by histology was performed. Images from MRI and histology were aligned, described, and quantitatively compared. In the three-dimensional MR images we directly show the presence of laminae and demonstrate that these are highly branching and are absent from much of the subepicardium. We visualized these MRI volumes to demonstrate laminar architecture and quantitatively demonstrated that the structural features observed are similar to those imaged in histology. We showed qualitatively and quantitatively that laminar architecture is similar in the four hearts. MRI can be used to image the laminar architecture of ex vivo hearts in three dimensions, and the images produced are qualitatively and quantitatively comparable with histology. We have demonstrated in the rat that: 1) laminar architecture is consistent between hearts; 2) myolaminae are absent from much of the subepicardium; and 3) although localized orthotropy is present throughout the myocardium, tracked myolaminae are branching structures and do not have a discrete identity.

NADH as an Endogenous Marker of Cardiac Tissue Injury at the Site of Radiofrequency Ablation

Atrial fibrillation (AF) remains the most commonly occurring cardiac arrhythmia; its incidence is associated with a lower quality of life including a higher rate of morbidity & mortality. Percutaneous left atrial catheter ablation for the purpose of eliminating AF has become a common treatment option and is currently being investigated for superiority over medical therapy in a large clinical trial. RFA produces lesions that can block the spread of electrical activity from the sites of abnormal activity including pulmonary veins. Today, there are limited means for real time monitoring of tissue injury during the RFA procedure. To address this need, we explored the fluorescence of endogenous NADH as a possible live marker of tissue injury during the ablation procedure. Studies were conducted in blood-free and blood-perfused isolated rat hearts. Epicardial RFA lesions were seen as areas of low NADH fluorescence which encompassed both irreversible and reversibly damaged tissue. Their size significantly exceeded TTC negative staining (TTC - Triphenyl Tetrazolium Chloride, a redox indicator used to differentiate between metabolically active and inactive tissues). Real-time monitoring of NADH fluorescence allowed visualization of gaps of viable tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical activity linked these gaps to the occurrence of post-ablation reentries. We conclude that fluorescence of endogenous NADH can assist visualization of injured epicardial tissue near the tip of the RFA catheter lesions.

Gastrointestinal system

The functions of the gastrointestinal (GI) tract include digestion, absorption, excretion, and protection. In this review, we focus on the electrical activity of the stomach and small intestine, which underlies the motility of these organs, and where the most detailed systems descriptions and computational models have been based to date. Much of this discussion is also applicable to the rest of the GI tract. This review covers four major spatial scales: cell, tissue, organ, and torso, and discusses the methods of investigation and the challenges associated with each. We begin by describing the origin of the electrical activity in the interstitial cells of Cajal, and its spread to smooth muscle cells. The spread of electrical activity through the stomach and small intestine is then described, followed by the resultant electrical and magnetic activity that may be recorded on the body surface. A number of common and highly symptomatic GI conditions involve abnormal electrical and/or motor activity, which are often termed functional disorders. In the last section of this review we address approaches being used to characterize and diagnose abnormalities in the electrical activity and how these might be applied in the clinical setting. The understanding of electrophysiology and motility of the GI system remains a challenging field, and the review discusses how biophysically based mathematical models can help to bridge gaps in our current knowledge, through integration of otherwise separate concepts.

Uterine Magnetomyography

Event Abstract Back to Event Uterine Magnetomyography Hari Eswaran1* 1 University of Arkansas for Medical Sciences, Department of Obstetrics and Gynaecology, United States The SARA System can record the magnetic field corresponding to the electrical activity of uterine contraction and provide requisite spatial-temporal information. The spatial-temporal information provided by the 151 channels will provide much more information about the contractile nature of the uterus than has previously been possible to obtain. Our preliminary studies show that by recording uterine magnetomyographic (MMG) signals we can localize the area of activation over the uterus during a contraction. This allows us explore the origin and propagation of uterine contraction despite the shifting of the pacemaker site from one contraction to another. We can localize the pacemaker by mapping the magnetic field distribution and quantify the spread by obtaining the percent of sensors active during each contraction with sensors spread over the entire maternal abdomen. Using this information, it will be possible to test the hypothesis that during most of pregnancy uterus is spontaneously active but because of limited propagation of the action potentials only small areas of myometrium is activated. Whereas closer to active labor, gap junction appear and increased number of myometrial cells are activated resulting increase in the spread of electrical activity over the uterus. This confirms that the uterus goes through a preparatory phase before labor starts. Conference: Biomag 2010 - 17th International Conference on Biomagnetism , Dubrovnik, Croatia, 28 Mar - 1 Apr, 2010. Presentation Type: Oral Presentation Topic: Fetal and neonatal biomagnetism Citation: Eswaran H (2010). Uterine Magnetomyography. Front. Neurosci. Conference Abstract: Biomag 2010 - 17th International Conference on Biomagnetism . doi: 10.3389/conf.fnins.2010.06.00094 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Mar 2010; Published Online: 23 Mar 2010. * Correspondence: Hari Eswaran, University of Arkansas for Medical Sciences, Department of Obstetrics and Gynaecology, Little Rock, United States, eswaranhari@uams.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hari Eswaran Google Hari Eswaran Google Scholar Hari Eswaran PubMed Hari Eswaran Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Channeling a New Focus for Heart Failure: Insights Into Ion Channels

Channeling a New Focus for Heart Failure: Insights Into Ion Channels

Embryogenesis of the Heart Muscle

This article concerns the development of myocardial architecture--crucial for contractile performance of the heart and its conduction system, essential for generation and coordinated spread of electrical activity. Topics discussed include molecular determination of cardiac phenotype (contractile and conducting), remodeling of ventricular wall architecture and its blood supply, and relation of trabecular compaction to noncompaction cardiomyopathy. Illustrated are the structure and function of the tubular heart, time course of trabecular compaction, and development of multilayered spiral systems of the compact layer.

Is There a Common Origin to Surround-Inhibition as Seen Through Electrical Activity Versus Hemodynamic Changes? Focus on “Duration-Dependent Response in SI to Vibrotactile Stimulation in Squirrel Monkey”

A common aspect of neocortical electrophysiology is that even a brief and spatially localized stimulus leads to activation that both outlives the stimulus and spreads well beyond the patch of cortex that receives direct afferent input. In this issue of the Journal of Neurophysiology , Simons et al

Modeling Cardiac Electrical Activity at the Cell and Tissue Levels

Significant tissue structures exist in cardiac ventricular tissue, which are of supracellular dimension. It is hypothesized that these tissue structures contribute to the discontinuous spread of electrical activation, may contribute to arrhythmogenesis, and also provide a substrate for effective cardioversion. However, the influences of these mesoscale tissue structures in intact ventricular tissue are difficult to understand solely on the basis of experimental measurement. Current measurement technology is able to record at both the macroscale tissue level and the microscale cellular or subcellular level, but to date it has not been possible to obtain large volume, direct measurements at the mesoscales. To bridge this scale gap in experimental measurements, we use tissue-specific structure and mathematical modeling. Our models, which can incorporate ion channel models at the cell level into the reaction-diffusion equations at the tissue level, have enabled us to consider key hypotheses regarding discontinuous activation.

‘The electrical spiral of the heart’: its role in the helical continuum.The hypothesis of the anisotropic conducting matrix

The study of the dissemination of the electrical impulse throughout the ventricular myocardium, which gave rise to the current theories, was carried out without taking into consideration the complex architecture of the cardiac muscle elucidated by more recent researchers. We propose a novel hypothesis based on the special macroscopic structure of the heart, the anisotropic electrical and mechanical behavior of the myocardium, the characteristics of the intercellular matrix and its very special collagen scaffolding, chemical composition, and biochemistry. The unique properties of the intercellular matrix would make it especially suited to function, in conjunction with the specialized conducting system (His-Purkinje system) as an efficient anisotropic conductor for the spread of electrical activation in the heart in order to allow an optimal sequence of excitation-contraction coupling that results in the coordination of effective myocardial contraction in birds and mammals of the most varied known heart rates. An analysis of certain clinical conditions that raise questions regarding current hypothesis and a review of novel techniques for recording transmembrane and extracellular potentials, which will provide a much firmer basis for the study of cardiac activation and the influence of myofiber architecture and which will allow in depth testing of hypotheses are presented.

Cardiac electrophysiology and tissue structure: bridging the scale gap with a joint measurement and modelling paradigm

Significant tissue structures exist in cardiac ventricular tissue that are of supracellular dimension. It is hypothesized that these tissue structures contribute to the discontinuous spread of electrical activation, may contribute to arrhymogenesis and also provide a substrate for effective cardioversion. However, the influences of these mesoscale tissue structures in intact ventricular tissue are difficult to understand solely on the basis of experimental measurement. Current measurement technology is able to record at both the macroscale tissue level and the microscale cellular or subcellular level, but to date it has not been possible to obtain large volume, direct measurements at the mesoscales. To bridge this scale gap in experimental measurements, we use tissue-specific structure and mathematical modelling. Our models have enabled us to consider key hypotheses regarding discontinuous activation. We also consider the future developments of our intact tissue experimental programme.