Cardiac microimpedance measurement in two-dimensional models using multisite interstitial stimulation (original) (raw)
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Feasibility of cardiac microimpedance measurement using multisite interstitial stimulation
AJP: Heart and Circulatory Physiology, 2004
This study was designed to test the hypothesis that analyses of central interstitial potential differences recorded during multisite stimulation with a set of interstitial electrodes provide sufficient data for accurate measurement of cardiac microimpedances. On theoretical grounds, interstitial current injected and removed using electrodes in close proximity does not cross the membrane, whereas equilibration of intracellular and interstitial potentials occurs distant from electrodes widely separated. Multisite interstitial stimulation should therefore give rise to interstitial potential differences recorded centrally that depend on intracellular and interstitial microimpedances, allowing independent measurement. Simulations of multisite stimulation with fine (25 μm) and wide (400 μm) spacing in one-dimensional models that included Luo-Rudy dynamic membrane equations were performed. Constant interstitial and intracellular microimpedances were prescribed for initial analyses. Discret...
A biophysical model for cardiac microimpedance measurements
AJP: Heart and Circulatory Physiology, 2010
Alterations to cell-to-cell electrical conductance and to the structural arrangement of the collagen network in cardiac tissue are recognized contributors to arrhythmia development, yet no present method allows direct in vivo measurements of these conductances at their true microscopic scale. The present report documents such a plan, which involves interstitial multisite stimulation at a subcellular to cellular size scale, and verifies the performance of the method through biophysical modeling. Although elements of the plan have been analyzed previously, their performance as a whole is considered here in a comprehensive way. Our analyses take advantage of a three-dimensional structural framework in which interstitial, intracellular, and membrane components are coupled to one another on the fine size scale, and electrodes are separated from one another as in arrays we fabricate routinely. With this arrangement, determination of passive tissue resistances can be made from measurements...
Quantification of Transmembrane Currents during Action Potential Propagation in the Heart
Biophysical Journal, 2013
The measurement, quantitative analysis, theory, and mathematical modeling of transmembrane potential and currents have been an integral part of the field of electrophysiology since its inception. Biophysical modeling of action potential propagation begins with detailed ionic current models for a patch of membrane within a distributed cable model. Voltage-clamp techniques have revolutionized clinical electrophysiology via the characterization of the transmembrane current gating variables; however, this kinetic information alone is insufficient to accurately represent propagation. Other factors, including channel density, membrane area, surface/volume ratio, axial conductivities, etc., are also crucial determinants of transmembrane currents in multicellular tissue but are extremely difficult to measure. Here, we provide, to our knowledge, a novel analytical approach to compute transmembrane currents directly from experimental data, which involves high-temporal (200 kHz) recordings of intra-and extracellular potential with glass microelectrodes from the epicardial surface of isolated rabbit hearts during propagation. We show for the first time, to our knowledge, that during stable planar propagation the biphasic total transmembrane current (I m) dipole density during depolarization was~0.25 ms in duration and asymmetric in amplitude (peak outward current was~95 mA/cm 2 and peak inward current was~140 mA/cm 2), and the peak inward ionic current (I ion) during depolarization was~260 mA/cm 2 with duration of~1.0 ms. Simulations of stable propagation using the ionic current versus transmembrane potential relationship fit from the experimental data reproduced these values better than traditional ionic models. During ventricular fibrillation, peak I m was decreased by 50% and peak I ion was decreased by 70%. Our results provide, to our knowledge, novel quantitative information that complements voltage-and patch-clamp data.
2007
To provide further insights into the impulse propagation between cardiac myocytes, we performed multiparametric studies of excitation spread with cellular resolution in confluent monolayers of cultured cardiomyocytes (CM). Simultaneous paired intracellular recordings of action potentials in two individual CM revealed slight periodic spontaneous advances/delays in the interspike time lag. Multisite field potential recordings performed with microelectrode arrays (MEA) confirmed random and iterative cycle-to-cycle changes in the direction of excitation spread. These local spontaneous variations in the cardiac impulse propagation pathways may be a safety process protecting against microscopically discontinuous conduction, and abnormality of this natural process could contribute to the genesis of some heart arrhythmias.
Preliminary Validation Using in vivo Measures of a Macroscopic Electrical Model of the Heart
Lecture Notes in Computer Science, 2003
This article describes an experimental protocol to obtain in vivo macroscopic measures of the cardiac electrical activity in a canine heart coupled with simulations done using macroscopic models of the canine myocardium. Electrical propagation simulations are conducted along with preliminary qualitative comparisons. Two different models are compared, one built from dissection and highly smoothed and one measured from Diffusion Tensor Imaging (DTI). We believe that validating a macroscopic model with in vivo measurements of the electrical activity should allow a future use of the model in a predictive way, for instance in radio-frequency ablation planning.
Cellular Physiology and Biochemistry, 2003
Background: Extracellular recordings of electrical activity with substrate-integrated microelectrode arrays (MEAs) enable non-invasive long-term monitoring of contracting multicellular cardiac preparations. However, to characterize not only the spread of excitation and the conduction velocity from field potential (FP) recordings, a more rigorous analysis of FPs is necessary. Therefore in this study we aim to characterize intrinsic action potential (AP) parameters by simultaneous recording of APs and FPs. Methods: A MEA consisting of 60 substrateintegrated electrodes is used to record the FPwaveform from multicellular preparations of isolated embryonic mouse cardiomyocytes. Simultaneous current clamp recordings in the vicinity of individual microelectrodes and pharmacological interventions allowed us to correlate FP and AP components and their time course. Results: The experiments revealed a linear relationship between AP rise time and FP rise time as well as a linear relationship between AP duration and FP duration. Furthermore a direct contribution of the voltage dependent Na +-and Ca 2+current to the FP could be identified. Conclusion: The characterization of the FP allows us for the first time to estimate AP changes and the contribution of individual current components to the AP by the help of non-invasive recording within a multicellular cardiac preparation during long-term culture.
The Journal of Physiology, 2002
Changes in transmembrane voltage (V m) of cardiac cells during electric field stimulation have a complex spatial-and time-dependent behaviour that differs significantly from electrical stimulation of space-clamped membranes by current pulses. A multisite optical mapping system was used to obtain 17 or 25 mm resolution maps of V m along the long axis of guinea-pig ventricular cells (n = 57) stained with voltage-sensitive dye (di-8-ANEPPS) and stimulated longitudinally with uniform electric field (2, 5 or 10 ms, 3-62 V cm _1) pulses (n = 201). The initial polarizations of V m responses (V mr) varied linearly along the cell length and reversed symmetrically upon field reversal. The remainder of the V m responses had parallel time courses among the recording sites, revealing a common time-varying signal component (V ms). V ms was depolarizing for pulses during rest and hyperpolarizing for pulses during the early plateau phase. V ms varied in amplitude and time course with increasing pulse amplitude. Four types of plateau response were observed, with transition points between the different responses occurring when the maximum polarization at the ends of the cell reached values estimated as 60, 110 and 220 mV. Among the cells that had a polarization change of > 200 mV at their ends (for fields > 45 V cm _1), some (n = 17/25) had non-parallel time courses among V m recordings of the various sites. This implied development of an intracellular field (E i) that was found to increase exponentially with time (t = 7.2 ± 3.2 ms). Theoretical considerations suggest that V ms represents the intracellular potential (f i) as well as the average polarization of the cell, and that V mr is the manifestation of the extracellular potential gradient resulting from the field stimulus. For cells undergoing field stimulation, f i acts as the cellular physiological state variable and substitutes for V m , which is the customary variable for space-clamped membranes.
Experimental Physiology, 2006
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.
Virtual electrode effects in myocardial fibers
Biophysical Journal, 1994
The changes in transmembrane potential during a stimulation pulse in the heart are not known. We have used transmembrane potential sensitive dye fluorescence to measure changes in transmembrane potential along fibers in an anisotropic arterially perfused rabbit epicardial layer. Cathodal or anodal extracellular point stimulation produced changes in transmembrane potential within 60 pm of the electrode that were positive or negative, respectively. The changes in transmembrane potential did not simply decrease to zero with increasing distance, as would occur with a theoretical fiber space constant, but instead became reversed beyond approximately 1 mm from the electrode consistent with a virtual electrode effect. Even stimulation from a line of terminals perpendicular to the fibers produced negative changes in transmembrane potential for cathodal stimulation with the largest negative changes during a 50-ms pulse at 3-4 mm from the electrode terminals. Negative changes as large as the amplitude of the action potential rising phase occurred during a 50-ms pulse for 20-volt cathodal stimulation. Switching to anodal stimulation reversed the directions of changes in transmembrane potential at most recording spots, however for stimulation during the refractory period negative changes in transmembrane potential were significantly larger than positive changes in transmembrane potential. Anodal stimulation during diastole with 3-ms pulses produced excitation in the region of depolarization that accelerated when the stimulation strength was increased to >3 times the anodal threshold strength. Thus, virtual electrode effects of unipolar stimulation occur in myocardial fibers, and for sufficiently strong stimuli the virtual electrode effects may influence electrical behavior of the myocardium.
A microdevice for studying intercellular electromechanical transduction in adult cardiac myocytes
2013
Intercellular electromechanical transduction in adult cardiac myocytes plays an important role in regulating heart function. The efficiency of intercellular electromechanical transduction has so far been investigated only to a limited extent, which is largely due to the lack of appropriate tools that can quantitatively assess the contractile performance of interconnected adult cardiac myocytes. In this paper we report a microengineered device that is capable of applying electrical stimulation to the selected adult cardiac myocyte in a longitudinally connected cell doublet and quantifying the intercellular electro-mechanical transduction by measuring the contractile performance of stimulated and un-stimulated cells in the same doublet. The capability of applying selective electrical stimulation on only one cell in the doublet is validated by examining cell contractile performance while blocking the intercellular communication. Quantitative assessment of cell contractile performance in isolated adult cardiac myocytes is performed by measuring the change in cell length. The proof-of-concept assessment of gap junction performance shows that the device is useful in studying the efficiency of gap junctions in adult cardiac myocytes, which is most relevant to the synchronized pumping performance of native myocardium. Collectively, this work provides a quantitative tool for studying intercellular electromechanical transduction and is expected to develop a comprehensive understanding of the role of intercellular communication in various heart diseases.