Publications
346 results found
Cooper PJ, Epstein A, MacLeod IA, et al., 2006, Soft tissue impact characterisation kit (STICK) for ex situ investigation of heart rhythm responses to acute mechanical stimulation, Vol: 90, Pages: 444-468, ISSN: 0079-6107
Both mechanical induction and mechanical termination of arrhythmias have been reported in man. Examples include pre-cordial impacts by sports implements (baseballs, pucks) that can trigger arrhythmias, including ventricular fibrillation, or via the so-called pre-cordial thump, used as an emergency resuscitation measure to convert arrhythmias to normal sinus node rhythm. These interventions have been partially reproduced in experimental studies on whole animals. Relating observations at the system's level to underlying mechanisms has been difficult, however, largely because of. (i) a deficit in efficient and affordable pharmacological agents to selectively target (sub-)cellular responses in whole animal studies, and (ii) the lack of suitable experimental models to study the above responses at intermediate levels of functional and structural integration, such as the isolated heart or cardiac tissue. This paper presents a soft tissue impact characterisation. kit (STICK), suitable for quantitative investigations into the effects of acute mechanical stimulation on cardiac electro-mechanical function in rodent isolated heart or tissue preparations. The STICK offers independent control over a range of relevant biophysical parameters, such as impact location and energy, pre-impact projectile speed and contact area, as well as over the timing of a mechanical stimulus relative to the cardiac cycle (monitored via electrocardiogram, ECG, here recorded directly from the cardiac surface). Projectile deceleration upon interaction with the tissue is monitored, contact-free, with a resolution of 175 mu m, providing information on tissue deformation dynamics, force, pressure and work of the mechanical intervention. In order to study functional effects of cardiac mechanical stimulation in the absence of tissue damage, impacts must be limited (for juvenile Guinea pig heart) to 2-2.5 mJ in the slack left ventricle (diastolic impact) and 5-10 mJ in contracture (systolic impact), as confi
Gavaghan D, Garny A, Maini PK, et al., 2006, Mathematical models in physiology, Vol: 364, Pages: 1099-1106, ISSN: 1364-503X
Computational modelling of biological processes and systems has witnessed a remarkable development in recent years. The search-term (modelling OR modeling) yields over 58 000 entries in PubMed. with more than 34 000 since the year 2000: thus, almost two-thirds of papers appeared in the last 5-6 years, compared to only about one-third in the preceding 5-6 decades. The development is fuelled both by the continuously improving tools and techniques available for bio-mathematical modelling and by the increasing demand in quantitative assessment of element inter-relations in complex biological systems. This has given rise to a worldwide public domain effort to build a computational framework that provides a comprehensive theoretical representation of integrated biological function-the Physiome. The current and next issues of this journal are devoted to a small sub-set of this initiative and address biocomputation and modelling in physiology, illustrating the breadth and depth of experimental data-based model development in biological research from sub-cellular events to whole organ simulations.
Iribe G, Kohl P, Noble D, 2006, Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic reticulum Ca2+ handling and interval-force relations: a modelling study, Vol: 364, Pages: 1107-1133, ISSN: 1364-503X
We hypothesize that slow inactivation of Ca2+/calmodulin-dependent kinase II (CaMKII) and its modulatory effect on sarcoplasmic reticulum (SR) Ca2+ handling are important for various interval-force (I-F) relations, in particular for the beat interval dependency in transient alternans during the decay of post-extrasystolic potentiation. We have developed a mathematical model of a single cardiomyocyte to integrate various I-F relations, including alternans, by incorporating a conceptual CaMKII kinetics model into the SR Ca2+ handling model. Our model integrates I-F relations, such as the beat interval-dependent twitch force duration, restitution and potentiation, positive staircase phenomenon and alternans. We found that CaMKII affects more or less all I-F relations, and it is a key factor for integration of the various I-F relations in our model. Alternans arises, in the model, out of a steep relation between SR Ca2+ load and release, owing to SR, load-dependent changes in the releasability of Ca2+ via the ryanodine receptor. Beat interval-dependent CaMKII activity, owing to its kinetic properties and amplifying effect on SR. Ca2+ load dependency of Ca2+ release, replicated the beat interval dependency of alternans, as observed experimentally. Additionally, our model enabled reproduction of the effects of various interventions on alternans, such as the slowing or accelerating of Ca2+ release and/or uptake. We conclude that a slow time-dependent factor, represented in the model by CaMKII, is important for the integration of I-F relations, including alternans, and that our model offers a useful tool for further analysis of the roles of integrative Ca2+ handling in myocardial I-F relation.
Camelliti P, Green CR, Kohl P, 2006, Structural and functional coupling of cardiac myocytes and fibroblasts, Vol: 42, Pages: 132-149, ISSN: 0065-2326
Cardiac myocytes and fibroblasts form extensive networks in the heart, with numerous anatomical contacts between cells. Fibroblasts, obligatory components of the extracellular matrix, represent the majority of cells in the normal heart, and their number increases with aging and during disease. The myocyte network, coupled by gap junctions, is generally believed to be electrically isolated from fibroblasts in vivo. In culture, however, the heterogeneous cell types form functional gap junctions, which can provide a substrate for electrical coupling of distant myocytes, interconnected by fibroblasts only. Whether similar behavior occurs in vivo has been the subject of considerable debate. Recent electrophysiological, immunohistochemical, and dye-coupling data confirmed the presence of direct electrical coupling between the two cell types in normal cardiac tissue (sinoatrial node), and it has been suggested that similar interactions may occur in post-infarct scar tissue. Such heterogeneous cell coupling could have major implications on in vivo electrical impulse conduction and the transport of small molecules or ions in both the normal and pathological myocardium. This review illustrates that it would be wrong to adhere to a scenario of functional integration of the heart that does not allow for a potential active contribution of non-myocytes to cardiac electrophysiology, and proposes to focus further research on the relevance of non-myocytes for cardiac structure and function. Copyright (c) 2006 S. Karger AG, Basel.
, 2005, Electrical coupling of fibroblasts and myocytes: relevance for cardiac propagation, JOURNAL OF ELECTROCARDIOLOGY, Vol: 38, Pages: 45-50, ISSN: 0022-0736
Kohl P, 2005, Recognition and prevention of Commotio cordis., Heart Rhythm, Vol: 2, ISSN: 1547-5271
Solovyova O, Kohl P, Konovalov P, et al., 2005, Slow responses to the mechanical interaction between heterogeneous heart segments, Vol: 19, Pages: A556-A557, ISSN: 0892-6638
Iribe G, Kohl P, 2005, Dynamic force/length control of isolated cardiomyocytes, Vol: 88, Pages: 120A-120A, ISSN: 0006-3495
Camelliti P, Borg TK, Kohl P, 2005, Structural and functional characterisation of cardiac fibroblasts, Vol: 65, Pages: 40-51, ISSN: 0008-6363
Cardiac fibroblasts form one of the largest cell populations, in terms of cell numbers, in the heart. They contribute to structural, biochemical, mechanical and electrical properties of the myocardium. Nonetheless, they are often disregarded by in vivo and in vitro studies into cardiac function. This review summarizes our understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
Camelliti P, McCulloch AD, Kohl P, 2005, Microstructured cocultures of cardiac myocytes and fibroblasts: A two-dimensional in vitro model of cardiac tissue, Vol: 11, Pages: 249-259, ISSN: 1431-9276
Cardiac myocytes and fibroblasts are essential elements of myocardial tissue structure and function. In vivo, myocytes constitute the majority of cardiac tissue volume, whereas fibroblasts dominate in numbers. In vitro, cardiac cell cultures are usually designed to exclude fibroblasts, which, because of their maintained proliferative potential, tend to overgrow the myocytes. Recent advances in microstructuring of cultures and cell growth on elastic membranes have greatly enhanced in vitro preservation of tissue properties and offer a novel platform technology for producing more in vivo-like models of myocardium. We used microfluidic techniques to grow two-dimensional structured cardiac tissue models, containing both myocytes and fibroblasts, and characterized cell morphology, distribution, and coupling using immunohistochemical techniques. In vitro findings were compared with in vivo ventricular cyto-architecture. Cardiac myocytes and fibroblasts, cultured on intersecting 30-mu m-wide collagen tracks, acquire an in vivo-like phenotype. Their spatial arrangement closely resembles that observed in native tissue: Strands of highly aligned myocytes are surrounded by parallel threads of fibroblasts. In this in vitro system, fibroblasts form contacts with other fibroblasts and myocytes, which can support homogeneous and heterogeneous gap junctional coupling, as observed in vivo. We conclude that structured cocultures of cardiomyocytes and fibroblasts mimic in vivo ventricular tissue organization and provide a novel tool for in vitro research into cardiac electromechanical function.
Cooper PJ, Kohl P, 2005, Species- and preparation-dependence of stretch effects on sino-atrial node pacemaking, Communicative Cardiac Cell, Editors: Sideman, Beyar, Landesberg, Pages: 324-335, ISBN: 1-57331-547-8
Acute dilation of the right atrium (e.g., via increased venous return) raises spontaneous beating rate (BR) of the heart in many species. Neural mechanisms contribute to this behavior in vivo, but a positive chronotropic response to stretch can also be observed in isolated right atrial tissue preparations and even at the level of single sino-atrial node (SAN) cells. The underlying mechanism has previously been reported to be compatible with stretch-activation of cation nonselective ion channels (SAC). This review reports species peculiarities in the chronotropic response of isolated SAN tissue strips to stretch: in contrast to guinea pig, murine SAN preparations respond to distension with a reduction in spontaneous BR. This differential response need not necessarily involve disparate (sub-)cellular mechanisms, as SAC activation would occur against the background of very different SAN electrophysiology in the two species. On the basis of single SAN cell action potential recordings, this review illustrates how this may give rise to potentially opposing effects on spontaneous BR. Interestingly, streptomycin (a useful SAC blocker in isolated cells) has no effect on stretch-induced chronotropy in situ, and this is interpreted as an indication of protection of SAC, in native tissue, from interaction with the drug.
Cooper PJ, Solovyova OE, Kohl P, 2005, Differential effects of stretch on spontaneous sino-atrial node beating rate: mouse vs Guinea pig, Vol: 88, Pages: 291A-291A, ISSN: 0006-3495
Garny A, Noble D, Kohl P, 2005, Dimensionality in cardiac modelling, Vol: 87, Pages: 47-66, ISSN: 0079-6107
The development of mathematical models of the heart has been an ongoing concern for many decades. The initial focus of this work was on single cell models that incorporate varyingly detailed descriptions of the mechanisms that give rise to experimentally observed action potential shapes. Clinically relevant heart rhythm disturbances, however, are multicellular phenomena, and there have been many initiatives to develop multidimensional representations of cardiac electromechanical activity. Here, we discuss the merits of dimensionality, from 0D single cell models, to 1D cell strands, 2D planes and 3D volumes, for the simulation of normal and disturbed rhythmicity. We specifically look at models of: (i) the origin and spread of cardiac excitation from the sino-atrial node into atrial tissue, and (ii) stretch-activated channel effects on ventricular cell and tissue activity. Simulation of the spread of normal and disturbed cardiac excitation requires multicellular models. 1D architectures suffer from limitations in neighbouring tissue effects on individual cells, but they can (with some modification) be applied to the simulation of normal spread of excitation or, in ring-like structures, re-entry simulation (colliding wave fronts, tachycardia). 2D models overcome many of the limitations imposed by models of lower dimensionality, and can be applied to the study of complex co-existing re-entry patterns or even fibrillation. 3D implementations are closest to reality, as they allow investigation of scroll waves. Our results suggest that 2D models offer a good compromise between computational resources, complexity of electrophysiological models, and applicability to basic research, and that they should be considered as an important stepping-stone towards anatomically detailed simulations. This highlights the need to identify and use the most appropriate model for any given task. The notion of a single and ultimate model is as useful as the idea of a universal mechanical tool
Protsenko YL, Routkevitch SM, Gur'ev VY, et al., 2005, Hybrid duplex: a novel method to study the contractile function of heterogeneous myocardium, Vol: 289, Pages: H2733-H2746, ISSN: 0363-6135
Hybrid duplex: a novel method to study the contractile function of heterogeneous myocardium. Am J Physiol Heart Circ Physiol 289: H2733-H2746, 2005. First published July 22, 2005; doi:10.1152/ajpheart. 00306.2005. -In an earlier study, we experimentally mimicked the effects of mechanical interaction between different regions of the ventricular wall by allowing pairs of independently maintained cardiac muscle fibers to interact mechanically in series or in parallel. This simple physiological model of heterogeneous myocardium, which has been termed "duplex," has provided new insight into basic effects of cardiac electromechanical heterogeneity. Here, we present a novel " hybrid duplex," where one of the elements is an isolated cardiac muscle and the other a " virtual cardiac muscle." The virtual muscle is represented by a computational model of cardiomyocyte electromechanical activity. We present in detail the computer-based digital control system that governs the mechanical interaction between virtual and biological muscle, the software used for data analysis, and working implementations of the model. Advantages of the hybrid duplex method are discussed, and experimental recordings are presented for illustration and as proof of the principle.
Moskvin A, Philipiev M, Solovyova O, et al., 2005, Electron-conformational model of cooperative cardiac ryanodine receptors gating, Vol: 19, Pages: A560-A560, ISSN: 0892-6638
Kohl P, Camelliti P, Burton FL, et al., 2005, Electrical coupling of fibroblasts and myocytes: relevance for cardiac propagation, Vol: 38, Pages: 45-50, ISSN: 0022-0736
Myocytes, while giving rise to the bulk volume of normal cardiac muscle, form a "minority cell population" in the heart compared with nonmyocytes, chiefly fibroblasts. The heterogeneous cell types show very intimate spatial interrelation in situ, with virtually every myocyte in the mammalian heart bordering to 1 or more fibroblasts. Nonetheless, gap junction coupling in the heart is traditionally assumed to occur exclusively between myocytes. Yet, both freshly isolated cells and cell cultures have unambiguously shown functional heterogeneous myocyte-fibroblast coupling (mainly via connexin 43). Such coupling is sufficient, in vitro, to synchronize spontaneous beating in distant myocytes, connected over distances of up to 300 mu m by Fibroblasts only. More recently, functional myocyte-fibroblast coupling (via connexin 45) has been demonstrated in situ for sinoatrial node Pacemaker tissue, and preliminary immunohistochemical data suggest that myocyte-fibroblast coupling may be present in postinfarct scar tissue. The functional relevance of such heterogeneous coupling for cardiac electrophysiology is only starting to emerge and has thus far mainly been assessed in theoretical studies. According to this research, fibroblasts may affect the origin and spread of excitation in several ways above and beyond formation of "passive" barriers that obstruct electrical conduction. Thus, fibroblasts may act as Current sinks, contributing to the formation of unidirectional block or to the delay in atrioventricular conduction. Via short-range interaction, fibroblasts may help to smooth out propagating wave fronts, in particular in the sinoatrial node and in the cross-sheet direction of healthy ventricular myocardium, 2 tissues that might otherwise be expected to show fragmented conduction patterns. As long-distance communication lines, fibroblasts may bridge posttransplantation or ischemic scar tissue, with beneficial or detrimental effects on organ function (dep
Camelliti P, Kohl P, 2004, Interrelation of cardiac fibroblasts and myocytes: New tools and insights, Pages: 1398-1399, ISSN: 1431-9276
Kohl P, Garny A, Trayanova N, 2004, (How) do computer models help us to understand arrhythmias?, Vol: 36, Pages: 740-740, ISSN: 0022-2828
Trayanova N, Li WH, Eason J, et al., 2004, Effect of stretch-activated channels on defibrillation efficacy, Vol: 1, Pages: 67-77, ISSN: 1547-5271
OBJECTIVES This study aims to explore whether defibrillation threshold elevation could be caused by sustained recruitment of stretch-activated channels (SACs) and, if so, what are the underlying mechanisms. BACKGROUND Clinical studies have demonstrated that patients with dilated and overloaded ventricles have elevated defibrillation threshold. Prolonged ventricular stretch has been suggested as a possible factor in defibrillation threshold elevation; however, its role remains unclear. METHODS A two-dimensional finite-element bidomain model of ventricular defibrillation was used in the study. Retaining the geometrical parameters in the model, defibrillation dose-response curves were constructed with and without SACs to isolate the effect of stretch on shock outcome. RESULTS Simulations demonstrate that SAC activation leads to flattening of dose-responise curve and increases in defibrillation threshold and effective dose for defibrillation by 31.4% and 18.8%, respectively. Examination of the electrophysiologic properties associated with sustained SAC recruitment pinpointed the main mechanisms responsible for the decrease in defibrillation efficacy. The lower conduction velocity of the shock-induced break excitations and the more positive transmembrane potential at the end of the effective refractory period in the tissue with SACs are proposed as main reasons for defibrillation threshold elevation. CONCLUSIONS Demonstrating the contribution of SACs to defibrillation threshold elevation identifies SACs as an attractive pharmaceutical target to reduce defibrillation threshold in patients with dilated cardiomyopathy. (C) 2004 Elsevier Inc. All rights reserved.
Camelliti P, Devlin GP, Matthews KG, et al., 2004, Spatially and temporally distinct expression of fibroblast connexins after sheep ventricular infarction, Vol: 62, Pages: 415-425, ISSN: 0008-6363
Objectives: Myocardial infarction leads to extensive changes in the organization of cardiac myocytes and fibroblasts, and changes in gap junction protein expression. In the immediate period following ischemia, reperfusion causes hypercontraction, spreading the necrotic lesion. Further progressive infarction continues over several weeks. In reperfusion injury, the nonspecific gap junction channel uncoupler heptanol limits necrosis. We hypothesize that gap junction coupling and fibroblast invasion provide a substrate for progressive infarction via a gap junction mediated bystander effect. Methods: A sheep coronary occlusion infarct model was used with samples collected at 12, 24 and 48 h, and 6, 12 and 30 d (days) post-infarction. lmmunohistochemical labelling of gap junction connexins Cx40, Cx43, and Cx45 was combined with cell-specific markers for fibroblasts (anti-vimentin) and myocytes (anti-myomesin). Double and triple immunolabelling and confocal microscopy were used to follow changes in cardiac myocyte morphology, fibroblast content and gap junction expression after myocardial infarction. Gap junction protein levels and fibroblast numbers were quantified. Results: Within 12 h of ischemia, myocyte viability is impaired within small islands in the ischemic region. These islands spread and fuse into larger infarct zones until 12 d post-infarction. Thereafter, surviving myocytes within the infarct and in the border-zone appear to become stabilized. Distant from the infarct, continuing myocyte disruption is regularly observed, even after 30 d. Cx43 becomes redistributed from intercalated discs to the lateral surface of structurally compromised myocytes within 12 d. Cx45 expressing fibroblasts infiltrate the damaged region within 24 h, becoming most numerous at 6-12 d post-infarction, with peak Cx45 levels at 6 d. Later, Cx43 expressing fibroblasts are observed, and the related Cx43 label increases over the 30 d observation period, even though fibroblast numbers decl
Camelliti P, Green CR, LeGrice I, et al., 2004, Fibroblast network in rabbit sinoatrial node - Structural and functional identification of homogeneous and heterogeneous cell coupling, Vol: 94, Pages: 828-835, ISSN: 0009-7330
Cardiomyocytes form a conducting network that is assumed to be electrically isolated from nonmyocytes in vivo. In cell culture, however, cardiac fibroblasts can contribute to the spread of excitation via functional gap junctions with cardiomyocytes. To assess the ability of fibroblasts to form gap junctions in vivo, we combine in situ detection of connexins in rabbit sinoatrial node ( a tissue that is particularly rich in fibroblasts) with identification of myocytes and fibroblasts using immunohistochemical labeling and confocal microscopy. We distinguish two spatially distinct fibroblast populations expressing different connexins: fibroblasts surrounded by other fibroblasts preferentially express connexin40, whereas fibroblasts that are intermingled with myocytes largely express connexin45. Functionality of homogeneous and heterogeneous cell coupling was investigated by dye transfer in sinoatrial node tissue explants. These studies reveal spread of Lucifer yellow, predominantly along extended threads of interconnected fibroblasts ( probably via connexin40), and occasionally between neighboring fibroblasts and myocytes ( probably via connexin45). Our findings show that cardiac fibroblasts form a coupled network of cells, which may be functionally linked to myocytes in rabbit SAN.
Boulin C, Epstein A, Dilling W, et al., 2004, Impactor design for Commotio cordis studies in isolated heart, Vol: 86, Pages: 297A-297A, ISSN: 0006-3495
Cooper PJ, Kohl P, 2004, Stretch-induced acceleration of sino-atrial node pacemaker rate: species and temperature-dependence, Vol: 86, Pages: 297A-297A, ISSN: 0006-3495
Garny A, Kohl P, 2004, For rat's sake: building an artificial heart, Pages: 31-32, ISSN: 0302-0797
Garny A, Kohl P, 2004, Mechanical induction of arrhythmias during ventricular repolarization - Modeling cellular mechanisms and their interaction in two dimensions, Cardiac Engineering: From Genes and Cells to Structure and Function, Editors: Sideman, Beyar, Pages: 133-143, ISBN: 1-57331-480-3
Nonpenetrating mechanical stimulation of the precordial chest is particularly likely to instantaneously induce sustained rhythm disturbances if timed to coincide with ventricular repolarization. A number of possible mechanisms have been proposed, including mechanoelectric feedback acting via stretch-activated ion channels. The cellular effects of such channel activation have been studied and mathematically modeled in great detail. In this study, we investigate their dynamic interaction with the trailing wave of action potential repolarization in a two-dimensional model of ventricular tissue. The model identifies how stretch activation of cation-non selective ion channels causes ectopic excitation in fully repolarized tissue and functional block of conduction at the intersection of the mechanical stimulus and the repolarization wave end, which may give rise to both trigger and sustaining mechanisms of ventricular arrhythmia. Simulation of stretch activation of K+-selective ion channels alone is insufficient in causing instantaneous arrhythmia, although it may, via action potential shortening, contribute to its sustenance.
Iribe G, Cooper PJ, Kohl P, 2004, Diastolic stretch causes transient increase in sarcoplasmic reticulum Ca2+ content without concurrent rise in resting Ca2+ (i) in isolated guinea-pig ventricular myocytes, Vol: 86, Pages: 136A-136A, ISSN: 0006-3495
Iribe G, Cooper PJ, Kohl P, 2004, Diastolic stretch causes transient increase in sarcoplasmic reticulum Ca2+ content without concurrent rise in resting Ca2+ (i) in isolated guinea-pig ventricular myocytes, Vol: 86, Pages: 136A-136A, ISSN: 0006-3495
King AM, Loiselle DS, Kohl P, 2004, Force generation for locomotion of vertebrates: Skeletal muscle overview, Vol: 29, Pages: 684-691, ISSN: 0364-9059
Locomotion is essential for vertebrate survival. Forces required for movement are generated by skeletal muscle. Skeletal muscle shortening and/or force generation occur via parallel sliding of two protein filaments: actin and myosin. This is driven by the cycling of cross-bridges, whose unitary nanometer length change and picoNewton force output are fueled by conversion of chemical energy, stored in the form of adenosine triphosphate, into a change in myosin protein configuration. The range of force and length changes of a muscle is determined by factors such as muscle cross section, fiber angle, tendon attachment, and lever geometry, but also by the metabolic pathways available for adenosine triphosphate synthesis and by enzymes involved in cross-bridge cycling. In addition, muscle mechanical activity is affected by the extent of actin and myosin filament overlap. Force output can be graded by selective recruitment of motor units and/or by variation of force output from individual units. The cost of locomotion is subject to species differences and is affected by the environment and form of movement, with an energy efficiency of up to 0.4. Overall, design principles of vertebrate skeletal muscle may serve as an interesting reference point for novel actuator technologies.
Kohl P, 2004, Cardiac cellular heterogeneity and remodelling, Vol: 64, Pages: 195-197, ISSN: 0008-6363
Li WH, Kohl P, Trayanova N, 2004, Induction of ventricular arrhythmias following mechanical impact: A simulation study in 3D, Vol: 35, Pages: 679-686, ISSN: 1567-2379
Commotio cordis, mechanical induction of heart rhythm disturbances, including sudden cardiac death, in the absence of corresponding structural damage, has been reported with increasing frequency in young individuals participating in sporting activities. Recently, the electrophysiological changes during c. cordis have been attributed to mechano-electric feedback, and particularly, to the recruitment of stretch-activated ion channels. The underlying mechanisms, however, by which a mechanical impact results in ventricular fibrillation, remain unknown. This study employs a 3D realistic model of rabbit ventricular geometry and fiber orientation to elucidate the electrophysiological mechanisms involved in arrhythmia induction following acute mechanical stimulation of the heart. Impact effects are modeled through stretch-activated ion channel activation in a 3D region of the ventricles representing the impact pro le. Both cation-nonselective and potassium-selective stretch-activated ion channels are recruited upon mechanical impact. The impact is administered at various coupling intervals following pacing at the apex. To aid in the interpretation of results, the effect of mechanical stimulation on single cell action potentials is also examined. The results demonstrate that the region of impact is characterized by different types of cellular responses, including generation of a new action potential, shortening, or lengthening of action potential duration. The impact induces sustained reentry only when (1) a new activation is elicited by mechanical stimulation ( caused by activation of cation-nonselective stretch-activated ion channels), and (2) upon return to the original region of impact, this activation does not encounter an extension of action potential duration (prevented by activation of potassium-selective stretch-activated ion channels).
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.