| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
SPECIAL COMMUNICATIONS
Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland 21205
Submitted 15 October 2002 ; accepted in final form 24 February 2003
 |
ABSTRACT |
|---|
 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
arrhythmia; cardiac electrophysiology; voltage-sensitive dye; optical mapping
The use of cultured monolayers of cardiac cells as a simplified model for the study of functional cardiac electrophysiology offers many advantages, including: 1) control of the cell microenvironment, 2) elimination of excitation-contraction decouplers that are used for optical mapping but may alter the electrophysiological properties of the cells (17, 18), 3) removal of large scale tissue heterogeneities such as blood vessels, connective tissue, or rotational anisotropy, and 4) the certainty that the electrophysiological signals are produced from a known layer of cells, thus enabling a one-to-one correspondence with two-dimensional computer simulations and nonlinear dynamic theory. Currently, there is a gap between the computer simulations, which assume an ideal homogeneous excitable media, and tissue experiments, where local tissue heterogeneity (e.g., anatomic obstacles, anisotropy, and heterogeneous electrophysiological characteristics) affects the global behavior of the reentry. The cell monolayer is a cellular network model that bridges the gap between computer models, single cells, and intact tissue, and provides the opportunity to characterize functional tissue electrophysiology in a controlled in vitro setting. The uniform isotropic cell monolayers presented in this study provide a relatively homogeneous and featureless medium that can act as a basis for the controlled manipulation of heterogeneity, including but not limited to addition of anisotropy (8) and well-defined anatomic obstacles (20).
Optical mapping has been performed on cultured monolayers of cardiac cells, but has relied mainly on microscope systems to record from a small region with high spatial resolution (25). The intense illumination required to achieve a good signal causes bleaching of the voltage-sensitive dye and phototoxic effects and limits the total recording time to a few hundred milliseconds. In a previous study (10), we introduced the technique of contact fluorescence imaging to record transmembrane potentials and electrical propagation at a macroscopic scale in confluent monolayers of neonatal rat ventricular myocytes, in which anatomic reentry could be observed.
The goal of the current study was to utilize optical mapping to characterize functional reentry that was induced and terminated by electrical pulses in this cultured cell model. We find that stable functional reentries can be generated with single-loop or figure-of-eight patterns. The reentries can be sustained and periodically observed over an extended period of time (>30 min), which allows accurate measurement of the reentry characteristics. Our model system represents a promising tool for studying cardiac reentry dynamics, antiarrhythmic drug screening, and the design of novel electrical, pharmacological, and molecular strategies for the treatment of cardiac arrhythmias. Portions of this study have been presented previously in abstract form (15, 16).
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
Electrophysiological recording. Coverslips were visually inspected under a microscope. Monolayers with obvious gaps in coverage were rejected. The coverslips were placed in a custom-designed chamber, stained with 8 µM RH-237 voltage-sensitive dye (Molecular Probes; Eugene, OR) for 5 min and continuously superfused with warmed (33 ± 1.5°C) oxygenated Tyrode solution consisting of (in mM) 135 NaCl, 5.4 KCl, 1.8 CaCl2, 1 MgCl2, 0.33 NaH2PO4, 5 HEPES, and 5 glucose. Field stimulation was applied with two parallel platinum plates placed 3.2 cm apart on either side of the coverslip. Unipolar point stimulation was applied with the use of a platinum electrode positioned just above the monolayer and a return line electrode at the side of the chamber.
Action potentials were recorded from 61 sites with the use of a modification of the contact fluorescence imaging method that was previously published (10). The recording chamber was placed directly above a fiber optic bundle, with fibers arranged in a 17-mm-diameter hexagonal array (Fig. 1). A 250-W quartz tungsten halogen lamp with an interference filter (530 ± 25 nm) delivered excitation light to the chamber via a liquid-filled light guide. A Plexiglas cover was placed on top of the chamber to stabilize the solution surface and reduce optical artifacts. The bottom of the chamber and the front end of the fiber bundle were painted with red ink (Avery Dennison; Brea, CA) to attenuate the excitation light and pass the red emission signal. Optical signals were low-pass filtered at 500 Hz and amplified with four custom-designed 16-channel printed circuit boards. Signals were sampled at 1 kHz and digitized with a 64-channel, 16-bit analog-to-digital board (Sheldon Instruments; San Diego, CA). Data were stored, displayed, and analyzed using software written in Visual Basic/Visual C++ (Microsoft; Redmond, WA).
Experimental protocol. A 2-s recording was initially made. If
spontaneous activity with frequency >2 Hz was present, the monolayer was
excluded. Ten-millisecond suprathreshold monophasic pulses were subsequently
used for stimulation throughout the experiment. Electrical pulses were applied
at 2 Hz through field (4–5 V/cm) or point (12–16 V) electrodes for
basic assessment of the culture. Failure of two or more adjacent channels to
respond to stimulation resulted in exclusion of the monolayer. To induce
reentry, a field stimulus (S1) was followed by a point stimulus (S2) applied
to the center of the monolayer, with an initial coupling interval of
80–120 ms. The coupling interval was increased iteratively by 10 ms if
there was no response to S2 and decreased by 5 ms if S2 produced an action
potential that propagated across the monolayer. The vulnerable period for
induction of sustained or nonsustained reentry was usually only a few
milliseconds long. In monolayers with spontaneous activity (<2 Hz), the
cells were first overdriven at a slightly higher rate for 
30 s.
Reentry was considered to be successfully induced if it lasted >5 rotations, to be sustained if it lasted >30 s, and to be stable if the coefficient of variation (ratio between the standard deviation and mean) of cycle length (CL) was <5%. To terminate a sustained reentry, the following were applied in sequential order: four separate 6.2 V/cm field pulses, four 9.4 V/cm pulses, four 12.5 V/cm pulses; short 6.2 V/cm field bursts at frequencies of 0.5 and 1 Hz above the frequency of the reentry; four separate 20-V point pulses; and short point bursts at frequencies of 0.5 and 1 Hz above the reentry rate. During and after each of the above, a 10-s recording was made to check whether the reentry had terminated or changed its characteristics. If termination was successful, induction was attempted again with the same S1-S2 protocol, as previously described.
Data analysis. Baseline drift was reduced by subtraction of a straight line from the optical signal. Isopotential maps were constructed by interpolation of the data from the 61 recording sites. Animations of electrical propagation were generated from signals that were band-pass filtered between 5 and 15 Hz. The activation time was defined as the instant of maximum positive slope. CL and action potential duration (APD) at 80% repolarization (APD80) were determined as the average of individual beats over a 5-s interval for all episodes of stable reentry. The coefficient of variation of CL was measured during a 5-s interval and used as an index of reentry stability. CL and APD80 before the induction of reentry were determined over a 2-s interval during 2-Hz point pacing.
The relative activation times at each recording point of the hexagonal array were used to calculate a velocity vector for each triangle defined by three neighboring points. The difference in activation times between pairs of neighboring points was determined as the delay that resulted in the maximum cross-correlation in signals of the two sites over a 5-s interval. To compare velocities among different episodes (either in the same monolayer or among different monolayers), a velocity index (VI) was calculated as the trimmed mean (after the lowest and highest 10th percentile were excluded) of the distribution of velocity magnitudes across the monolayer.
A global measure of the electrical activity of the cell monolayer was calculated in the form of a bipolar pseudo-ECG (pECG) by using the method of lead fields (19). In effect, the pECG was calculated as the potential difference between virtual recording electrodes placed on opposite edges of the coverslip (situated on the bottom of a semi-infinite volume conductor), at a distance of one-half of the radius of the coverslip above the surface. Mathematically, the lead potentials were determined as the integral of the dot product between the lead field (the field produced by reciprocal energization of the leads) and the bioelectric sources, represented as the spatial gradient in transmembrane potential, divided by the bath conductivity.
Data are expressed as means ± SE unless stated otherwise. The statistical significance of changes in the measured parameters (APD80 and VI) before and after reentry was determined with the use of a paired Student's t-test. The difference in the measured parameters for single-loop versus figure-of-eight reentry was assessed by an unpaired t-test. P values <0.05 were considered to be significant.
|
RESULTS |
|---|
|
TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
Thirty-five of the sustained episodes of reentry were electrically induced by a single pair of the S1 field, S2 point shocks, whereas the remaining four arose spontaneously. Of the 24 episodes for which the induction phase was captured, 8 were figure-of-eight and 16 were single-loop reentry patterns. Two of the figure-of-eight induction episodes converted spontaneously to single-loop reentry, whereas the other six episodes stabilized.
Figure 3 illustrates an induction process and follows the progression of the activation wave front (see http://ajpheart.physiology.org/cgi/content/full/00896.2002/DC1). After a field shock was applied (frame 2), a planar wave front progressed from the lower right to the upper left of the monolayer (frames 3–9), after which S2 was applied near the center of the monolayer (frame 10). In the next two frames, the ensuing wave front progressed only toward the bottom of the monolayer, due to the unidirectional block in the wake of the previous planar wave. In frame 12, the wave front reached the bottom of the monolayer and split into two wavelets, which then rotated and moved up the sides of the monolayer (frame 14). In frame 15, the two wavelets met at the center of the monolayer, and another rotation of the figure-of-eight began. The last row of Fig. 3 shows another one-half rotation of the reentry. After the initial stimulation (first action potential), three rotations of the figure-of-eight pattern occurred (Fig. 3B). During the third rotation, the cores drifted, and the direction of the rotation of the figure-of-eight reversed (solid arrow in Fig. 3C). After three more rotations, one of the cores anchored (open arrow), the other core moved off the monolayer, and the reentry continued as a single-loop reentry.
|
In three cases, in which only nonsustained episodes of reentry could be induced, the addition of a small (1 mm) hole in the center of the monolayer (made by scratching with a needle) enabled the induction of sustained and stationary reentry episodes. The initial phases of the nonsustained episodes were virtually identical to the initial phases of sustained episodes on the same monolayer except for a lack of anchoring and subsequent drift of the core.
Reentry rate varied during the induction phase of reentry and decreased in 20 of 22 episodes (a decelerating trend), with decay constant of 7.5 ± 0.4 beats. In those cases, the CL (inverse of reentry rate) increased by a factor of 1.25 ± 0.09 (difference from 1, P < 0.01) from the first full rotation of reentry to its steady-state condition.
After reentry had stabilized, a 5-s recording of reentrant activity was used to characterize each episode. Of the 39 episodes of stable reentry, 32 were single loop and 7 were figure-of-eight. Averaging across all monolayers, the mean APD80 was 106 ± 11 ms (n = 18) before induction and 132 ± 11 ms (n = 18) during reentry (P < 0.005). The ratio of APD80 after induction to APD80 before induction was 1.34 ± 0.14 (difference from 1, P < 0.02). In 18 monolayers, VI was measured both before (during 2-Hz point pacing) and after induction of reentry and had mean values of 17.4 ± 2.1 and 12.2 ± 1.1 cm/s, respectively (P < 0.002). Sustained reentries showed a high degree of stability and reproducibility. Coefficient of variation of the CL was measured in 20 episodes, of which 17 had values <5% (mean 2 ± 1%), signifying a highly stable and regular reentry after the induction phase. In one coverslip, 11 episodes of sustained reentry were induced. The reentries occurred over a time span of >15 min, and they all behaved in a similar fashion, with the same pivot point and direction of rotation. The means ± SD for CL, APD80, and VI were 390 ± 14 ms, 92 ± 7 ms, and 12.8 ± 0.35 cm/s, corresponding to coefficient of variations of 4%, 7%, and 2%, respectively.
Figure 4A (see also http://ajpheart.physiology.org/cgi/content/full/00896.2002/DC1) depicts one rotation of a stable, stationary single loop reentry taken from a 5-s recording (Fig. 4, B and C). The curved reentrant wave front is revealed in the isochrone map (Fig. 4D) and velocity field (Fig. 4E). Figure 5 (see also http://ajpheart.physiology.org/cgi/content/full/00896.2002/DC1) depicts a stable and stationary figure-of-eight reentry (through 1 1/2 rotations). The common pathway of the reentry is oriented diagonally from the lower left to the upper right quadrant. The wave breaks into two wavelets (frame 5) that travel down the left and right sides of the monolayer (frames 6–8). The two wavelets then collide in the left lower quadrant (frame 9), and another cycle begins. The single site optical recording (Fig. 5B) and the pECG (Fig. 5C) are similar to those from the single-loop reentry (Fig. 4, B and C), indicating that a stable, stationary figure-of-eight pattern can also produce monomorphic tachycardia-like activity (5).
|
|
The mean CLs during single-loop and figure-of-eight reentry were 358 ± 33 ms (n = 18 monolayers) and 311 ± 78 ms (n = 4 monolayers), respectively (not significant). The APD80 and VI were 118 ± 12 ms and 12.9 ± 1.0 cm/s during single-loop reentry (n = 18) and 137 ± 18 ms and 7.8 ± 1.3 cm/s during figure-of-eight reentry (n = 4). The difference in VIs for the two types of reentry was statistically significant (P = 0.03), whereas the difference in APD80 values was not. The VI before the induction of the reentry was 19.4 ± 4.3 cm/s (n = 14) for the monolayers with single-loop reentry and 10.1 ± 2.6 cm/s (n = 4) for the monolayers with figure-of-eight reentry (P = 0.06).
To terminate reentry, electrical shocks were applied to 35 of the sustained reentry episodes according to the termination protocol (field shocks, field pacing, point shocks, and point pacing). In 21 episodes (60%), the electrical shock(s) successfully terminated the reentry. In 13 of 21 episodes, the first field shock succeeded, whereas in the remaining 8 episodes, 4 were eventually terminated by a repeated single-field shock, 1 with field pacing, 3 by a single point shock, but none with point pacing. These results indicate that most often the first few applied shocks terminated the reentry episodes. The nonterminated episodes received an average of 11 single field shocks before the switch to field pacing. However, rapid pacing had a very low success rate of termination if single field pulses were already unsuccessful.
The CL, APD, and VI of the electrically terminated (n = 21) and nonterminated (n = 14) reentry episodes were nearly indistinguishable (351 ± 19 ms, 113 ± 9 ms, and 12.5 ± 0.7 cm/s vs. 354 ± 42 ms, 117 ± 11 ms, and 11.6 ± 1.1 cm/s, respectively). The mean calculated diastolic interval (DIc = CL - APD80) was 238 and 237 ms for terminated and nonterminated episodes, respectively. Therefore, it was not possible to predict the outcome of a reentry episode to shock based solely on the overall properties of the reentry wave. Other observed effects of shocks included resetting, direction reversal, and conversion of a single loop into a figure-of-eight pattern.
|
DISCUSSION |
|---|
|
TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Our induction protocol consisted of a field S1, followed by a point S2 stimulus, which theoretically should produce a figure-of-eight reentry in homogeneous isotropic media (26, 28, 29, 35, 36). This protocol differs from that used in the clinic, i.e., rapid point pacing with premature stimuli at progressively shorter intervals from the same electrode (13, 34). The clinical protocol relies on preexisting heterogeneity in cellular or tissue properties (e.g., excitability, refractory period, or anisotropy) that on rapid pacing cause the formation of a wave break.
In this study, a figure-of-eight reentry was induced in only 8 of 24 cases, whereas in the remaining cases a single-loop reentry was induced. It is possible that the second wavelet immediately hit a refractory region or a border of the monolayer and extinguished before forming a second counterrotating loop. Two episodes of figure-of-eight reentry did in fact convert to single-loop reentry after two to three rotations. During the induction phase, nearly all (20/22) of the single-loop reentries in monolayers exhibited a deceleration in reentry rate with a decay constant of adaptation of 7.5 beats. CL increased by an average of 25%. Our results are consistent with data from rabbit atrium (1) and canine ventricle (31), which show decelerating trends in rate during the onset of functional reentry.
The phenomenon of anchoring has an important role in stabilization of
reentry and corresponds to fixation of the reentry core to a single location.
In this study, stationary spiral waves were commonly observed with the
creation of a <1-mm obstacle and also appeared in the absence of any added
obstacle, contrary to a previous study
(14) in the canine atrium,
which showed that spiral waves can attach to an obstacle and become stationary
only if the obstacle size is >3 mm. However, it has been suggested that the
likelihood for anchoring will increase with decreasing thickness of tissue
(32,
37). Computer simulations
suggest that in homogeneous media with small obstacle size, reentry will be
less stable (with quasiperiodic behavior and spiral wave breakup) if the slope
of the restitution curve is >1
(38). We did not observe any
such complex behavior. During reentry, the VI decreased compared with its
value before the induction of reentry (12.2 ± 1.1 and 17.4 ± 2.1
cm/s, respectively, P < 0.002). This effect is likely a
consequence of rate- or positive curvature-dependent slowing of conduction
velocity. The ratio of APD80 during reentry (132 ms for an average
reentry frequency of 3 Hz) to its value before induction of reentry (106
ms during pacing at 2 Hz) was 1.34 (P < 0.02). This result may be
a manifestation of reverse frequency dependence of APD80 in
neonatal rat cardiac myocytes in our experimental setting, consistent with
previous reports (21,
30) on adult rat myocytes.
The monolayers, which sustained more than one reentrant loop (figure-of-eight) had significantly lower VIs than those with only a single loop (7.8 ± 2.5 vs. 12.9 ± 3.0 cm/s; P < 0.05). These differences also existed in the two groups of monolayers before reentry induction (10.1 ± 2.6 vs. 19.4 ± 4.3 cm/s, respectively), suggesting that a lower preexisting VI may predispose the monolayer to sustain more than one reentry circuit. APD80 was not significantly different for the two groups of monolayers. Other explanations for a lower VI during figure-of-eight reentry include a rate dependence of velocity or the existence of two reentrant circuits, which reduces the path length available for each reentry loop and increases wave front curvature.
The experimental cell culture model allows the effect of shock on reentry to be studied in a controlled fashion. In 60% of the attempts, the reentry was terminated by electrical shocks, predominantly by a single field pulse. Field pacing terminated only 1 of 18 episodes, although it was attempted in all cases when single pulses did not succeed. This result suggests that if a reentry episode in this model system is susceptible to electrical termination, it can be terminated by a properly timed, single shock, and that pulse trains may not substantially improve the success rate. In addition, there was no significant difference in reentry characteristics (CL, APD, VI, and calculated diastolic interval) between the terminated and the nonterminated episodes. Hence, the reason for the relatively high failure rate (40%) of electrical termination could be from improperly chosen parameters of the termination protocol that was used (e.g., direction of field, field strengths, timing of shock delivery, position of the point electrode relative to the reentry core, pacing frequency, etc.), or particular characteristics of the reentry (e.g., size of the excitable gap). Because most of the terminated episodes received only one shock, and because the nonterminated episodes received an average of 11 shocks, an insufficient number of shocks probably is not a factor in the failure to terminate an episode. The specific factors responsible for shock success or failure await further study.
The sustained reentries were both stable (small variation in reentry characteristics over time) and reproducible (similar behavior on the same coverslip). These features make it possible to perform quantitative experiments on the effect of reentry modifiers, such as electrical shock and pharmacological manipulation.
Limitations. A drawback of the contact fluorescent imaging technique is the relatively low spatial resolution of imaging, which in our study was 1 mm at 2-mm intervals. This resolution allowed us to have a relatively large field of view (17 mm) with a relatively small number of recording sites. However, the trajectory of the spiral tip, which has been the subject of numerous theoretical studies, was not well resolved.
Another potential limitation of this study is the intrinsic difference in neonatal rat versus human cardiac electrophysiology. Neonatal rat cardiac cells demonstrate a triangular action potential with little plateau, predominance of transient outward repolarization current, and insignificant delayed rectifier current (11). Nevertheless, the fundamental biophysics of reentry may not be critically dependent on the particular cell type, and many theoretical models of reentry dynamics are derived not from ionic current models, but rather from reduced models such as the Fitzhugh-Nagumo model. Hence, the rigor and reproducibility of the cultured cell preparation may ultimately outweigh the possible disadvantages of a nonhuman electrophysiological model in terms of an improved understanding of the critical factors that govern functional reentry in the heart.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Present address for S. Iravanian: St. Luke's Roosevelt Hospital Center, 1000 Tenth Ave., Dept. of Medicine, New York, NY 10019.
Present address for Y. Nabutovsky: St. Jude Medical, 705 E. Evelyn Ave., Sunnyvale, CA 94086.
|
REFERENCES |
|---|
|
TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. Weinberg, S. Iravanian, and L. Tung Representation of Collective Electrical Behavior of Cardiac Cell Sheets Biophys. J., August 1, 2008; 95(3): 1138 - 1150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Nakagami, H. Tanaka, P. Dai, S.-F. Lin, T. Tanabe, H. Mani, K. Fujiwara, H. Matsubara, and T. Takamatsu Generation of reentrant arrhythmias by dominant-negative inhibition of connexin43 in rat cultured myocyte monolayers Cardiovasc Res, July 1, 2008; 79(1): 70 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. N. Biktashev, A. Arutunyan, and N. A. Sarvazyan Generation and Escape of Local Waves from the Boundary of Uncoupled Cardiac Tissue Biophys. J., May 1, 2008; 94(9): 3726 - 3738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Cysyk and L. Tung Electric Field Perturbations of Spiral Waves Attached to Millimeter-Size Obstacles Biophys. J., February 15, 2008; 94(4): 1533 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kizana, C. Y. Chang, E. Cingolani, G. A. Ramirez-Correa, R. B. Sekar, M. R. Abraham, S. L. Ginn, L. Tung, I. E. Alexander, and E. Marban Gene Transfer of Connexin43 Mutants Attenuates Coupling in Cardiomyocytes: Novel Basis for Modulation of Cardiac Conduction by Gene Therapy Circ. Res., June 8, 2007; 100(11): 1597 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Smith, L. Barile, H. C. Cho, M. K. Leppo, J. M. Hare, E. Messina, A. Giacomello, M. R. Abraham, and E. Marban Regenerative Potential of Cardiosphere-Derived Cells Expanded From Percutaneous Endomyocardial Biopsy Specimens Circulation, February 20, 2007; 115(7): 896 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Pollard and R. C. Barr Cardiac microimpedance measurement in two-dimensional models using multisite interstitial stimulation Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1976 - H1987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Bian and L. Tung Structure-Related Initiation of Reentry by Rapid Pacing in Monolayers of Cardiac Cells Circ. Res., March 3, 2006; 98(4): e29 - e38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bursac and L. Tung Acceleration of functional reentry by rapid pacing in anisotropic cardiac monolayers: Formation of multi-wave functional reentries Cardiovasc Res, February 1, 2006; 69(2): 381 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pumir, A. Arutunyan, V. Krinsky, and N. Sarvazyan Genesis of Ectopic Waves: Role of Coupling, Automaticity, and Heterogeneity Biophys. J., October 1, 2005; 89(4): 2332 - 2349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Abraham, C. A. Henrikson, L. Tung, M. G. Chang, M. Aon, T. Xue, R. A. Li, B. O' Rourke, and E. Marban Antiarrhythmic Engineering of Skeletal Myoblasts for Cardiac Transplantation Circ. Res., July 22, 2005; 97(2): 159 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-R. Kong, N. Bursac, and L. Tung Mechanoelectrical excitation by fluid jets in monolayers of cultured cardiac myocytes J Appl Physiol, June 1, 2005; 98(6): 2328 - 2336. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
