Skip Navigation

Cardiovascular Research 2002 53(1):202-208; doi:10.1016/S0008-6363(01)00439-4
© 2002 by European Society of Cardiology
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by di Bernardo, D.
Right arrow Articles by Murray, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by di Bernardo, D.
Right arrow Articles by Murray, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2001, European Society of Cardiology

Origin on the electrocardiogram of U-waves and abnormal U-wave inversion

Diego di Bernardo and Alan Murray*

Regional Medical Physics Department, Freeman Hospital, Newcastle-upon-Tyne NE7 7DN, UK

alan.murray{at}ncl.ac.uk

* Corresponding author. Tel.: +44-191-284-3111; fax: +44-191-213-0290

Received 12 June 2001; accepted 2 August 2001


   Abstract
Top
 Abstract
1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Conclusion
 Acknowledgments
 References
 
Aims: Soon after the initial development of electrocardiography, U-waves were discovered in many normal subjects following the T-wave repolarisation waveform on the electrocardiogram. Various explanations have been offered for their origin, but none is universally accepted. We used our model of left ventricular repolarisation to explore the most common hypotheses for the genesis of U-waves. Methods: Recently, we have shown that a computer model of left ventricular repolarisation was able to explain the formation of the characteristic shape of the T-wave, and we have now used this model to explore the most common hypotheses for the genesis of U-waves. The repolarisation phase of the action potentials in the model exhibited an after-potential. We investigated separately the effect on the 12-lead electrocardiogram of three different features of the model: the amplitude of the after-potential; dispersion of repolarisation in the left ventricle ranging from 20 to 100 ms; the timing of the after-potential, relative to the end of the principal action potential component, ranging from –100 to 100 ms. Results: We show that delaying repolarisation in different regions of the heart cannot explain the U-wave, but show that the presence of after-potentials on the cardiac action potential do explain the U-wave polarity and other characteristic U-wave features. We also show that abnormal after-potential timing corresponds with abnormal U-wave inversion. Conclusion: Our model provides a realistic and simple solution to the problem of U-wave genesis.

KEYWORDS Computer modelling; Conduction system; ECG; Membrane potential; Repolarization; Stretch/m–e coupling


   1 Introduction
Top
 Abstract
 1 Introduction
2 Methods
 3 Results
 4 Discussion
 5 Conclusion
 Acknowledgments
 References
 
In the normal electrocardiogram (ECG), an extra deflection at the end of the obvious repolarisation sequence is often seen. This U-wave, as it was named by Einthoven in 1903 [1], is still the subject of debate almost 100 years later, as its origin is still uncertain and the various hypotheses underlying its origin are controversial [2].

The U-wave in normal subjects always has the same polarity as the T-wave, and so when the U-wave inverts with respect to the T-wave this is of diagnostic importance [3]. Currently, however, the main reason for studying the U-wave is to gain an insight into the underlying cardiac electrophysiology, as well as simply to resolve the speculation surrounding its origin. The hypotheses for U-wave genesis were reviewed by Surawicz [2]. There are three main hypotheses: late repolarisation of the Purkinje fibers [1], late repolarisation of some other portions of the left ventricle, and alterations in the normal action potential shape by after-potentials, which are most likely generated by mechano-electric feedback [4].

Involvement of the Purkinje fibres is the oldest proposal and is thought to be the least likely explanation. Lepeschkin [4] and Surawicz [2] listed many observations that make it difficult, if not impossible, to reconcile this proposal with the formation of U-waves. Late repolarisation of some other portions of the left ventricle was first proposed by Einthoven [1], and more recently by Antzelevitch and Sicouri [5] who attributed U-waves to the late repolarisation of M cells, found in the mid-myocardium. Lazzara [6] presented many arguments against the involvement of M cells by demonstrating that these cells prolong the T-wave rather than create distinct U-waves. In addition, recent experiments suggest that M cell action potential duration in vivo is not substantially different from those of normal myocardial cells [7–9].

Currently, the hypothesis involving after-potentials is most favoured [2], as it accords with the observation that mechanical events associated with ventricular wall motion are correlated with both U-waves on the surface ECG and also with after-potentials on the cardiac cellular action potential waveform [2,10]. Franz et al. [11] recorded after-potentials while mechanically stressing cardiac cells in an in vitro preparation. Cellular electrophysiologists have also discovered ionic transfer associated with these after-potentials [12]. However, firmer proof of the link between after-potentials and U-waves appearing on the body-surface ECG is still lacking.


   2 Methods
Top
 Abstract
 1 Introduction
 2 Methods
3 Results
 4 Discussion
 5 Conclusion
 Acknowledgments
 References
 
We have already proposed a computational model of left ventricular repolarisation [13], which successfully explained the formation and shape of the T-wave [14]. The model is described in the publications cited [13,14]. It uses an experimentally derived repolarisation sequence in a three-dimensional left ventricle, embedded in a three-dimensional torso, to produce 12-lead ECG T-waves. The torso surface was represented by a cylinder 50 cm tall with an elliptic cross-section (major diameter 34 cm, minor diameter 26 cm). It was considered electrically homogeneous and isotropic with a conductivity equal to 0.3 S/m. The left ventricle was modelled by a truncated ellipsoid representing the epicardium (height 10.6 cm truncated at 7.0 cm, major diameter 7.0 cm, minor diameter 6.6 cm). An approximately ellipsoidal cavity represented the endocardium. The left ventricle (LV) was considered electrically homogeneous and isotropic with an intracellular conductivity of 0.1 S/m and an extracellular conductivity of 0.2 S/m.

A single action potential template of a myocardial cell transmembrane action potential (AP) was associated with each point of the left ventricle. To model repolarisation, the left ventricle was set initially to be completely depolarised with all the action potentials in the plateau phase (phase 2). A specific repolarisation starting time was set for each point on the left ventricular surface (both epi- and endocardium) according to published experimental repolarisation sequences [15,16].

The global dispersion of repolarisation times in the model was varied by increasing the time delay between the first and the last region in the left ventricle to repolarise. The repolarisation starting times across the left ventricle between these two extreme regions were linearly interpolated.

We have now studied this model with after-potentials added to the action potentials of all cardiac cells, and hence have been able to examine the after-potential hypothesis for U-wave genesis. The hypothesis associated with late repolarisation in some portions of the left ventricle was also studied, by changing dispersion of repolarisation. In addition, we were able to research the effect of different delays between the normal action potential phases and the timing of the after-potential, which allowed us to investigate whether abnormal delays produced abnormal U-waves.

2.1 Model of action potentials
The repolarisation phase of the action potentials used in the model exhibited an after-potential. The repolarisation phase waveform chosen was similar to the one described experimentally by Franz et al. [11] during mechanical stretch of the myocardial cell. This was obtained as the sum of two components:

1. A normal action potential repolarisation phase, shown in Fig. 1 (middle panels), which was described mathematically as a product of exponential functions [17], whose parameters determine the shape and duration of the action potential.
2. An after-potential component (APC), shown in Fig. 1 (top panel), described as a product of exponential functions whose parameters determine its shape and duration.
By varying the magnitude of the APC, i.e. multiplying it by a constant scaling factor, we were able to obtain action potentials exhibiting different after-potential characteristics (Fig. 1, bottom panel). To quantify the amount of after-potential in an action potential, we used the H-ratio defined by Coraboeuf et al. [12]. The H-ratio measures the decrease in the slope at the end of the action potential repolarisation phase (phase 3) caused by an after-potential. A value of H-ratio equal to 0% indicates the absence of an after-potential, so that the action potential repolarises smoothly to its resting value. When the after-potential causes the slope just before the end of the action potential phase 3 to become horizontal, the H-ratio measures 100%. In this case the action potential will have a ‘flat hump’ just before returning to its resting values. A value of the H-ratio over 100% is possible and denotes a peaked hump (positive slope), associated with a net inward transmembrane current. Small values of the H-ratio indicate an action potential exhibiting a small after-potential, while large values of the H-ratio denote an action potential exhibiting a large after-potential. Examples of action potentials exhibiting after-potentials with different H-ratios are shown in Fig. 1.


Figure 1
View larger version (27K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Action potentials with simulated after-potentials used for the simulation of U-waves. Top panels: after potential components (APCs) for different values of the scaling factor and time shift. Middle panels: normal action potential (AP). Bottom panels: simulated APs exhibiting after-potentials obtained as the sum of the APCs with the normal AP. Last panel to the right shows a simulated AP exhibiting a delayed after-depolarisation (DAD) obtained with an APC shifted in time by +100 ms.

 
2.2 Simulations
Three sets of simulations of the 12-lead electrocardiograms were obtained as follows:
1. Changes in after-potential amplitude. The action potentials used exhibited after-potentials with values of H-ratio varying from 0% (no after-potential) to 98% (almost flat hump). This was achieved by varying the APC scaling factor from 0 to 1, with a 0.1-step. Dispersion of repolarisation was kept constant and equal to 20 ms, and no changes to the APC timing were made.
2. Changes in dispersion of repolarisation. We changed the value of maximum dispersion of repolarisation in the left ventricle from 20 to 100 ms in 20-ms steps. The H-ratio was kept constant at 98% (APC scaling factor of 1), and no changes to the APC timing were made. This simulation was repeated for the action potentials exhibiting after-potentials with values of the H-ratio less than 98%. The APC scaling factor was varied from 0 (H-ratio 0%) to 1.0 (H-ratio 98%) in 0.1-steps.
3. Changes in timing of after-potentials. We shifted the APC in time from –100 to 100 ms with a 20-ms step. For a –100-ms time shift of the APC, the resulting action potential had a notch interrupting its phase 2. This is shown in Fig. 1, third column. For a +100-ms time shift, the resulting AP had an after-potential beginning at completion of its repolarisation, i.e. this is equivalent to a delayed after-depolarisation (DAD). This is shown in Fig. 1, fourth column. Dispersion was kept constant and equal to 20 ms, and the APC scaling factor equal to 1.0.

2.3 Variation of action potential shape
The action potential shape was varied by separately changing the shape of its two components: normal action potential and APC. We modified the shape of these components by increasing and decreasing the exponential function parameters by 10%. Two action potentials with after-potentials were obtained by adding the normal action potential to the modified APCs and two others by adding the modified action potentials to the normal APC. To test whether the simulated U-waves were sensitive to changes in shape of the action potential with after-potential, we repeated the simulations described above, this time using each of the four modified action potentials. This allowed the computation of the mean and standard deviation (S.D.) of the characteristics measured on the U-waves.

2.4 Measurement of U-wave
To quantify the U-waves simulated by our model, the characteristics reported by Surawicz [2] were measured: U-wave duration (measured from the T-wave end to the U-wave end); T-wave end to U-wave peak interval; U-wave amplitude expressed as a percentage of the preceding T-wave amplitude. The following definitions were used: the T-wave end was defined as the nadir between the T-wave and the U-wave; the U-wave end as the return to the baseline.


   3 Results
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
4 Discussion
 5 Conclusion
 Acknowledgments
 References
 
3.1 Effects of after-potential amplitude
The after-potential H-ratio is a measure of the after-potential amplitude. In the left panels of Fig. 2, the effect of increasing the action potential H-ratio on the simulated U-wave is summarised: in the top panels, the action potential repolarisation phases for three different and increasing values of the after-potential H-ratio are shown together with the corresponding T- and U-waves simulated by the model. The larger the after-potential, the more distinct the U-wave on the simulated ECG leads. Panels A, B and C show the characteristics measured on the simulated U-waves in the precordial leads for values of after-potential H-ratio varying from 65 to 98%, and for a constant value of dispersion equal to 20 ms. Error bars show the S.D. of these characteristics, with varying model properties. U-wave duration varied from a mean of 185 to 228 ms, T-wave end to U-wave peak interval increased from 35 to 88 ms and U-wave amplitude as a percentage of T-wave amplitude increased from 8 to 18%. For a value of the H-ratio less than 65%, U-waves could not be differentiated from the T-waves.


Figure 2
View larger version (33K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Effect of after-potential amplitude (H-ratio) and of dispersion of repolarisation on the simulated U-waves. Action potentials and T and U-waves are shown (x-axis length 600 ms). For changing H-ratio, the dispersion was kept constant at 20 ms. For changing dispersion (first and last action potential to repolarise are shown), the after-potential H-ratio was kept constant and equal to 98%, corresponding to an APC scaling factor of 1.0. Error bars show the standard deviation of the parameters computed using the modified action potentials. There are no values for H-ratio below 65%, as the U-wave was not distinct from the T-wave.

 
3.2 Effects of dispersion of repolarisation
The right panels of Fig. 2 show the effect of increasing maximum dispersion of repolarisation on the simulated U-waves. In the top panels, the last AP in the left ventricle to repolarise is shown in addition to the first, to indicate the maximum dispersion of repolarisation. Simulated T- and U-waves are shown for values of dispersion equal to 20, 60, and 100 ms. Panels D, E and F show the characteristics measured on the U-waves in the precordial leads for values of dispersion ranging from 20 to 100 ms, with a constant value of after-potential H-ratio equal to 98%. Error bars show the S.D. of these characteristics with varying model properties. U-wave duration and the interval from the T-wave end to U-wave peak both decreased, indicating that the U-wave became closer to the T-wave. U-wave amplitude as a percentage of T-wave amplitude remained fairly constant with increasing dispersion.

This behaviour was also present for values of the after-potential H-ratio less than 98%. For values between 73 and 98%, U-wave duration and T-wave end to U-wave peak interval decreased by approximately only 14 ms for a change in dispersion from 20 to 100 ms. U-wave amplitude increased only slightly by 1%. For values of the after-potential H-ratio smaller than 73%, increasing the value of dispersion to 100 ms caused the U-wave to merge completely with the preceding T-wave and therefore to disappear. When no after-potential was present, i.e. H-ratio equal to 0%, the effect of increased dispersion of repolarisation was that of changing the shape of the T-waves by making them more symmetric [14]. No U-waves were, however, generated.

3.3 Effects of the timing of the after-potential
The effect of shifting in time the after-potential is summarised in Fig. 3, which shows the action potentials used for the simulations and the corresponding simulated T- and U-waves. Negative time shifts cause an interruption of the rising slope of the T-wave when more negative than –60 ms. Increasing the value above –40 ms, normal U-waves appear. For increasingly positive time shifts, the resulting action potentials exhibit a delayed after-depolarisation (DAD), and the nadir between the T and U-waves deepens until a clearly differentiated and inverted U-wave appears. Inverted U-waves are most clearly seen with an after-potential shifted by 100 ms and are similar to the inverted U-waves observed in hypertensive subjects [18].


Figure 3
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Simulated T- and U-waves for time shifted after-potentials. In all ECG panels lead V2 is shown (x-axis length 600 ms).

 
3.4 Variation of action potential shape
Error bars obtained by plotting the standard deviation of the characteristics computed from the U-waves simulated using the reference and four modified action potentials are shown in Fig. 2. The exact shapes of the two components used to generate the action potential exhibiting an after-potential are not critical for the generation of a U-wave.


   4 Discussion
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
5 Conclusion
 Acknowledgments
 References
 
U-waves generated by our model, for low values of dispersion, resemble closely those observed in normal subjects. Simulated U-waves have a shorter ascent than descent, in agreement with clinical observations [2], and the characteristics measured from our simulated U-waves are in the range of the ones measured by Surawicz [2] in normal subjects.

The model demonstrates that the after-potential theory is compatible with the generation of normal U-waves on the surface ECG. Our results show that an action potential (AP) exhibiting an after-potential prolonging its repolarisation phase is sufficient to generate normal U-waves in the 12-lead ECG. This is in agreement with observations obtained during hypokalemia, when prominent after-potentials appear on the AP [12] and prominent U-waves are observed on the surface ECG. Also, many experimental studies in long QT syndrome patients (LQTS) have shown that after-potentials exist when U-waves are present [19–22].

This work and our previous work on T-wave shape [14] show that increased dispersion of repolarisation is a very unlikely mechanism for the generation of U-waves. Increasing dispersion of repolarisation in the model without after-potentials caused T-wave shape to change and to become more symmetrical [14], but not a separate deflection to appear after the T-wave.

In our model, the left ventricle is homogeneous and isotropic. Therefore, we were able to use the surface source model [23] to compute the body surface electrocardiogram from a description of the cardiac electric sources on the heart surface only (both epi- and endocardium), while sources in the heart volume (transmural region) did not contribute directly to the surface electrocardiogram. It is possible that localised repolarisation delay in the transmural region could result in deflections appearing after the T-wave, if inhomogeneity and anisotropy of the myocardium were included in the model. Nesterenko and Antzelevitch [24] simulated such waves using a computer model of a 1x1-cm surface representing the transmural wall, with an inhomogeneous varying conductivity at the boundary of the M cells region. Although they did not give detailed results, their simulated U-waves [5] appeared asymmetrical with a longer ascent than descent, similar to a small version of the T-wave [2]. This is not compatible with clinical U-waves. The simulated U-waves in our study have shapes similar to those published for clinical U-waves, and these are a direct consequence of the presence of after-potentials on the action potential.

We were able to generate inverted U-waves and to attribute their origin to delayed after-depolarisations. To our knowledge, this is the first time an explanation for U-wave inversion has been proposed. Experimental studies [10] link prolonged ventricular mechanical diastole to inverted U-waves. One could speculate that this prolonged stretching causes a delay in the activation of stretch activated channels, thus causing the after-potential to become a DAD, which, as we show, causes inverted U-waves.

4.1 Limitations
The model of ventricular repolarisation used in this work is an oversimplification of the real heart. Inhomogeneity and anisotropy of the myocardium have not been modelled and only the left ventricle was simulated. It has been shown [25], however, that for the purpose of simulating the body surface electrocardiogram these simplifications are acceptable.

The sequence of left ventricular repolarisation used in the model is a simplification based on the work of Cowan et al. [15] where only the epicardium of the left ventricular free wall during repolarisation was mapped. The starting time of repolarisation on the endocardium is considered to be constant, but delayed from the epicardial repolarisation as indicated by other researchers [16]. This allowed the endocardium-to-epicardium repolarisation gradient to be simulated effectively.

The action potential used was identical over all the endocardial and epicardial surface. This is not likely to occur in a real heart [7,20]. Yet we have shown [14] that changes in action potential shape on the endocardial surface do not alter the simulated electrocardiogram appreciably.


   5 Conclusion
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Conclusion
Acknowledgments
 References
 
The introduction of dispersion of repolarisation, by delaying repolarisation in different regions of the heart cannot explain the U-wave, and if after-potentials are introduced, changes in dispersion change the U-wave characteristics by small amounts in comparison with changes in the after-depolarisation itself. However, the presence of after-potentials on the cardiac action potential do explain the U-wave polarity and other characteristic U-wave features. Also, abnormal after-potential timing corresponds with abnormal U-wave inversion. After-potentials have been previously linked to U-waves in patients, but not in healthy subjects. Moreover, until now, no experimental study has been designed to test the after-potential theory of U-wave genesis. This work provides, we believe for the first time, a computer model which shows that after-potentials can generate normal U-waves on the surface ECG, and therefore they may be responsible for U-waves also in normal subjects. This model was able to simulate U-waves with clinically normal characteristics and also abnormal inverted U-waves. Our model suggests a realistic and simple solution to this century old problem.

Time for primary review: 29 days.


   Acknowledgments
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Conclusion
 Acknowledgments
References
 
D.d.B. was supported by a post-graduate Marie Curie Fellowship granted by the European Commission (C.N. ERB4001GT971847).


   References
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 5 Conclusion
 Acknowledgments
 References
 

  1. Einthoven W. Die galvanometrische Registrierung des menschlichen Electrokardiogram. Pfluger's Arch (1903) 99:472–480.[CrossRef]
  2. Surawicz B. U-wave: facts, hypotheses, misconceptions, and misnomers. J. Cardiovasc. Electrophysiol. (1998) 9:1117–1128.[Web of Science][Medline]
  3. Kataoka H., Yano S. Associations between different status of myocardial ischemia and ischemia-related negative or positive epicardial U-waves. J. Electrocardiol (1999) 32:293–303.[CrossRef][Web of Science][Medline]
  4. Lepeschkin E. Advances in electrocardiology. Schlant R.C., Hurst J.W., eds. (1972) New York: Grune and Stratton. 431–448.
  5. Antzelevitch C., Sicouri S. Clinical relevance of cardiac arrhythmias generated by after-depolarisations: role of M cells in the generation of U-waves, triggered activity and torsade de pointes. J. Am. Coll. Cardiol. (1994) 23:259–277.[Abstract]
  6. Lazzara R. The U-wave and the M cell. J. Am. Coll. Cardiol. (1995) 26:193–194.[CrossRef][Web of Science][Medline]
  7. Anyukhovsky E.P., Sosunov E.A., Rosen M.R. Regional differences in electrophysiological properties of epicardium, midmyocardium, and endocardium — in vitro and in vivo correlations. Circulation (1996) 94:1981–1988.[Abstract/Free Full Text]
  8. Taggart P., Sutton P.M.T., Opthof T., et al. Transmural repolarisation in the left ventricle in humans during normoxia and ischemia. Cardiovasc. Res. (2001) 50:454–462.[Abstract/Free Full Text]
  9. Yan G., Shimizu W., Antzelevitch C. Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations. Circulation (1998) 98:1921–1927.[Abstract/Free Full Text]
  10. Choo M.H., Gibson D.G. U-waves in ventricular hypertrophy: possible demonstration of mechano-electrical feedback. Br. Heart J. (1986) 55:428–433.[Abstract/Free Full Text]
  11. Franz M., Burkhoff D., Yue D.T., et al. Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts. Cardiovasc. Res. (1989) 23:213–223.[Abstract/Free Full Text]
  12. Coraboeuf E., Deroueaix E., Coulombe A. Acidosis-induced abnormal repolarisation and repetitive activity in isolated dog Purkinje fibres. J. Physiol. (1980) 76:97–106.
  13. di Bernardo D., Murray A. A computer model for the study of cardiac repolarisation. J. Cardiovasc. Electrophysiol. (2000) 11:895–899.[CrossRef][Web of Science][Medline]
  14. di Bernardo D., Murray A. Explaining the T-wave shape in the ECG. Nature (2000) 403:40.[CrossRef][Medline]
  15. Cowan J.C., Hilton C., Griffiths C., et al. Sequence of epicardial repolarisation and configuration of the T wave. Br. Heart J. (1988) 60:424–433.[Abstract/Free Full Text]
  16. Franz M.R., Bargheer K., Rafflenbeul W., et al. Monophasic action potential mapping in human subjects with normal electrocardiograms: direct evidence for the genesis of the T wave. Circulation (1987) 75:379–386.[Abstract/Free Full Text]
  17. Wohlfart B. A simple model for demonstration of ST-T changes in the ECG. Eur. Heart J. (1987) 8:409–416.[Abstract/Free Full Text]
  18. Miwa K., Miyagi Y., Fujita M., et al. Transient terminal U-wave inversion as a more specific marker for myocardial ischemia. Am. Heart J. (1993) 125:981–986.[CrossRef][Web of Science][Medline]
  19. Habbab M.A., El-Sherif N. TU alternans, long QTU, and torsade de pointes: clinical and experimental observations. PACE (1992) 15:916–931.[Medline]
  20. Shimizu W., Ohe T., Kurita T., et al. Epinephrine-induced ventricular premature complexes due to early after-depolarisations and effects of verapamil and propranolol in a patient with congenital LQTS. J. Cardiovasc. Electrophysiol. (1994) 5:438–444.[Web of Science][Medline]
  21. Miwa D., Inoue T., Yokoyama M. Monophasic action potentials in patients with torsade de pointes. Jpn Circ. J. (1994) 58:248–258.[Medline]
  22. El-Sherif N., Zweiler R.H., Craelius W., Gough B.W., Henkin R. QTU prolongation and polymorphic ventricular tachyarrhythmias due to bradycardia-dependent early afterdepolarisations. Circ. Res. (1988) 63:286–305.[Abstract/Free Full Text]
  23. Simms H., Geselowitz D. Computation of heart surface potentials using the surface source model. J. Cardiovasc. Electrophysiol. (1995) 6:522–531.[CrossRef][Web of Science][Medline]
  24. Nesterenko V., Antzelevitch C. M-cells as the basis for the electrocardiographic U-wave. Circulation (1992) 86:I 302.
  25. Gulrajani R.M. Bioelectricity and biomagnetism. (1998) New York: Wiley.

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Med. Genet.Home page
C-W Lu, J-H Lin, Y S Rajawat, H Jerng, T G Rami, X Sanchez, G DeFreitas, B Carabello, F DeMayo, D L Kearney, et al.
Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome
J. Med. Genet., August 1, 2006; 43(8): 653 - 659.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
H. J. Ritsema van Eck, J. A. Kors, and G. van Herpen
The U wave in the electrocardiogram: A solution for a 100-year-old riddle
Cardiovasc Res, August 1, 2005; 67(2): 256 - 262.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by di Bernardo, D.
Right arrow Articles by Murray, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by di Bernardo, D.
Right arrow Articles by Murray, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?