Roles of Electric Field and Fiber Structure in Cardiac Electric Stimulation (original) (raw)
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Biophysical Journal, 1995
Recent theoretical models of cardiac electrical stimulation or defibrillation predict a complex spatial pattern of transmembrane potential (vm) around a stimulating electrode, resulting from the formation of virtual electrodes of reversed polarity. The pattern of membrane polarization has been attributed to the anisotropic structure of the tissue. To verify such model predictions experimentally, an optical technique using a fluorescent voltage-sensitive dye was used to map the spatial distribution of vm around a 1 50-pm-radius extracellular unipolar electrode. An S1 -S2 stimulation protocol was used, and vm was measured during an S2 pulse having an intensity equal to 1 Ox the cathodal diastolic threshold of excitation. The recordings were obtained on the endocardial surface of bullfrog atrium in directions parallel and perpendicular to the cardiac fibers. In the longitudinal fiber direction, the membrane depolarized for cathodal pulses (and hyperpolarized for anodal pulses) but only in a region within 445 + 1 12 pm (and 616 ± 78 pm for anodal pulses) from the center of the electrode (n = 9). Outside this region, Vm reversed polarity and reached a local maximum at 922 ± 136 pm (and 988 ± 117 pm for anodal pulses) (n = 9). Beyond this point vm decayed to zero over a distance of 1.5-2 mm. In the transverse fiber direction, the membrane depolarized for cathodal pulses (and hyperpolarized for anodal pulses) at all distances from the electrode. The amplitude of the response decreased with distance from the electrode with an exponential decay constant of 343 ± 1 10 pm for cathodal pulses and 253 ± 91 pm for anodal pulses (n = 7). The results were qualitatively similar in both fiber directions when the atrium was bathed in a solution containing ionic channel blockers. A two-dimensional computer model was formulated for the case of highly anisotropic cardiac tissue and qualitatively accounts for nearly all the observed spatial and temporal behavior of vm in the two fiber directions. The relationships between vm and both the "activating function" and extracellular potential gradient are discussed.
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.
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.
Intramural Virtual Electrodes in Ventricular Wall: Effects on Epicardial Polarizations
Circulation, 2004
Background— Intramural virtual electrodes (IVEs) are believed to play an important role in defibrillation, but their existence in intact myocardium remains unproven. Here, IVEs were detected by use of optical recordings of shock-induced transmembrane potential (V m ) changes (ΔV m ) measured from the intact epicardial heart surface. Methods and Results— To detect IVEs, isolated porcine left ventricles were sequentially stained with a V m -sensitive dye by 2 methods: (1) surface staining (SS) and (2) global staining (GS) via coronary perfusion. Shocks (2 to 50 V/cm) were applied across the ventricular wall in an epicardial-to-endocardial direction during the action potential plateau via transparent mesh electrodes, and shock-induced ΔV m were measured optically from the same epicardial locations after SS and GS. Optical recordings revealed significant differences between ΔV m of 2 types that became more prominent with increasing shock strength: (1) for weak shocks, SS-ΔV m were large...
Biophysical Journal, 2005
Transmembrane potential responses of single cardiac cells stimulated at rest were studied with uniform rectangular field pulses having durations of 0.5-10 ms. Cells were enzymatically isolated from guinea pig ventricles, stained with voltage sensitive dye di-8-ANEPPS, and stimulated along their long axes. Fluorescence signals were recorded with spatial resolution of 17 mm for up to 11 sites along the cell. With 5 and 10 ms pulses, all cells (n ¼ 10) fired an action potential over a broad range of field amplitudes (;3-65 V/cm). With 0.5 and 1 ms pulses, all cells (n ¼ 7) fired an action potential for field amplitudes ranging from the threshold value (;4-8 V/cm) to 50-60 V/cm. However, when the field amplitude was further increased, five of seven cells failed to fire an action potential. We postulated that this paradoxical loss of excitation for higher amplitude field pulses is the result of nonuniform polarization of the cell membrane under conditions of electric field stimulation, and a counterbalancing interplay between sodium current and inwardly rectifying potassium current with increasing field strength. This hypothesis was verified using computer simulations of a field-stimulated guinea pig ventricular cell. In conclusion, we show that for stimulation with short-duration pulses, cells can be excited for fields ranging between a low amplitude excitation threshold and a high amplitude threshold above which the excitation is suppressed. These results can have implications for the mechanistic understanding of defibrillation outcome, especially in the setting of diseased myocardium.
Heart Rhythm, 2006
BACKGROUND According to one hypothesized mechanism of defibrillation, shocks directly excite the bulk of ventricular myocardium in the excitable state due to intramural virtual electrodes; however, this hypothesis has not been examined in intact myocardium. OBJECTIVES The purpose of this study was examine the role of intramural virtual electrodes in shock-induced activation of intact left ventricular (LV) tissue. METHODS Twelve isolated porcine LV preparations were stained with a transmembrane potential (V m)-sensitive dye by two methods: (1) surface staining and (2) global staining via coronary perfusion. Shocks (E Ϸ0.8-48 V/cm, duration ϭ 10 ms) were applied across the wall from epicardium to endocardium during diastole via transparent electrodes. Shock-induced V m responses were measured optically from the intact epicardial surface after surface staining and global staining. RESULTS Surface-staining recordings demonstrated different V m responses to cathodal and anodal shocks. Whereas cathodal shocks caused depolarization and rapid activation of the epicardial surface, anodal shocks induced hyperpolarization and delayed surface activation. In contrast, global-staining V m responses to cathodal and anodal shocks were qualitatively similar. Both responses were characterized by activation with small latency and rapid propagation. Weak shocks of both polarities induced monotonic action potential upstrokes; stronger shocks induced nonmonotonic upstrokes with two rising phases at shock onset and end. Such features of global-staining V m responses as make activation of the epicardium by anodal shocks and the nonmonotonic action potential upstrokes can be explained by the presence of subepicardial intramural virtual electrodes. CONCLUSION These data suggest that shocks induce intramural virtual electrodes that directly excite LV tissue and account for the shape of optical V m responses recorded from the epicardial surface.
Transmembrane potentials during high voltage shocks in ischemic cardiac tissue
Pacing and clinical electrophysiology : PACE, 1997
Transmembrane, voltage sensitive fluorescent dye (TMF) recording techniques have shown that high voltage shocks (HVS), typically used in defibrillation, produce either hyper- or depolarization of the transmembrane potential (TMP) when delivered in the refractory period of an action potential (AP) in normal cardiac tissue (NT). Further, HVS produce an extension of the AP, which has been hypothesized as a potential mechanism for electrical defibrillation. We examined whether HVS modify TMP of ischemic tissue (IT) in a similar manner. In seven Langendorff rabbit hearts, recordings of APs were obtained in both NT and IT with TMF using di-4-ANEPPS, and diacetylmonoxime (23 microM) to avoid motion artifacts. Local ischemia was produced by occlusion of the LAD, HVS of either biphasic (5 + 5 ms) or (3 + 2 ms) or monophasic shapes (5 ms) were delivered at varying times (20%-90%) of the paced AP. Intracardiac ECG and TMF recordings of the TMP were each amplified, recorded, and digitized at a ...
Circulation, 2002
Background— It is believed that defibrillation is due to shock-induced changes of transmembrane potential (ΔV m ) in the bulk of ventricular myocardium (so-called virtual electrodes), but experimental proof of this hypothesis is absent. Here, intramural shock-induced ΔV m were measured for the first time in isolated preparations of left ventricle (LV) by an optical mapping technique. Methods and Results— LV preparations were excised from porcine hearts (n=9) and perfused through a coronary artery. Rectangular shocks (duration 10 ms, field strength E ≈2 to 50 V/cm) were applied across the wall during the action potential plateau by 2 large electrodes. Shock-induced ΔV m were measured on the transmural wall surface with a 16×16 photodiode array (resolution 1.2 mm/diode). Whereas weak shocks (E≈2 V/cm) induced negligible ΔV m in the wall middle, stronger shocks produced intramural ΔV m of 2 types. (1) Shocks with E>4 V/cm produced both positive and negative intramural ΔV m that chan...