Skip Navigation

Cardiovascular Research 2001 50(2):270-279; doi:10.1016/S0008-6363(01)00255-3
© 2001 by European Society of Cardiology
This Article
Right arrow Extract 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 Babuty, D.
Right arrow Articles by Lab, M. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Babuty, D.
Right arrow Articles by Lab, M. J
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2001, European Society of Cardiology

Mechanoelectric contributions to sudden cardiac death

Dominique Babutya,* and Max J Labb

aCardiologie B, CNRS UMR 6542, Hôpital Trousseau, 37044 Tours Cedex, France
bNational Heart and Lung Institute, Imperial College School of Science Technology and Medicine, Charing Cross Campus, London W6 8RF, UK

* Corresponding author. Tel.: +33-2-4747-4687; fax: +33-2-4747-5919 d.babuty{at}chu.med.univ-tours.fr

Received 28 September 2000; accepted 7 February 2001

KEYWORDS Arrhythmia (mechanisms); Mechanotransduction; Sudden death; Ventricular arrhythmias


   1 Introduction
Top
 1 Introduction
2 A common pathway:...
 3 Principle of mechanoelectric...
 4 Which factors are...
 5 Electrophysiological...
 6 Clinical correlates, sudden...
 7 Conclusions
 References
 
Sudden death, a major problem in developed countries and increasingly so in some underdeveloped countries, justifies research on the mechanisms and identification of patients at high risk of sudden death. Most sudden deaths are secondary to ventricular tachyarrhythmias [1,2]. Primary electrical disturbances, such as Brugada syndrome, long QT syndrome, are rare and account for few sudden deaths. Sudden death as a rule complicates the situation with an underlying cardiac disease with different classes of heart failure [2]. The alteration of the cardiac mechanical properties developing early in heart failure is accompanied by action potential lengthening [3], which is modulated by acute stretch [4–6].

The English theologian and philosopher William of Occam (1280–1349) stated: ‘Entia non sunt multiplicanda praeter necessitatum’. This is recognised as Occam's Razor. Roughly interpreted, it proposes that it is better to have one hypothesis to explain five observations than five hypotheses to explain each one. The cardiovascular clinical parameters used for predicting sudden arrhythmic death ranging through indices of neurohormonal status (i.e. heart rate variability) to indices of electrophysiological substrate (i.e. late potentials, QT dispersion, alternans) are influenced by and associated with mechanical disturbances in heart. Although some of these issues have been related to mechanical factors in previous reviews [6–12], this review describes the possibility that many of the mechano-arrhythmic factors affect a common pathway. Moreover, several arrhythmic mechanisms and their clinical correlates infringe such a pathway. That is, we will try to apply the Occam's Razor principle to this problem.


   2 A common pathway: mechanical heterogeneity?
Top
 1 Introduction
 2 A common pathway:...
3 Principle of mechanoelectric...
 4 Which factors are...
 5 Electrophysiological...
 6 Clinical correlates, sudden...
 7 Conclusions
 References
 
We have to satisfy several criteria to support this contention (Fig. 1). First, the currently accepted situation (Fig. 1A). The black arrows represent the paths taken by the conventional dogma. The etiological factors (Fig. 1A top centre), through a variety of mechanisms act via various clinical correlations (right hand side) and various electrophysiological arrhythmic mechanisms (left hand side). These clinical correlates act via arrhythmic mechanisms. On the other hands, arrhythmic mechanisms produce the clinical correlates (horizontal arrow) and so precipitate lethal arrhythmia (the two downward single black arrows to VF). An alternative proposal is represented in Fig. 1B. In this thesis, the aeteological factors produce cardiac mechanical changes (downward black arrow). These represent a common factor that links the clinical correlates with arrhythmic mechanisms (the two looped black arrows) by involving electromechanical dispersion as indicated in the symbolic ‘ventricle’. This common link produces lethal arrhythmias (downward white block arrow).


Figure 1
View larger version (25K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Diagram of Aetiology interacting with arrhythmic mechanisms and clinical correlates. (A) Broad current situation. The aeteological factors (top centre) produce (top arrows) both the arrhythmic mechanisms (left oblong) and the clinical correlates (right oblong), which are somehow related (horizontal grey link). The arrhythmic mechanisms include trigger mechanisms and electrical dispersion (elect disp — left lower arrow to diagrammatic heart). This can lead (small vertical white arrow) to ventricular fibrillation (VF). (B) Proposed possible alternative. The aeteological factors (top centre) produce (downward straight arrow) mechanical changes (mechanical causes). These produce the arrhythmic mechanisms as well as their clinical correlates (looped arrows). The loops continue down to diagrammatic heart to produce VF via mechanoeletric dispersion (‘mechan’ first) via mechanoelectric feedback (small horizontal curved arrows inside diagrammatic heart).

 
These changes fall within two broad categories which are linked together. First, the diverse factors contributing to or correlate with arrhythmia formation interact with mechanoelectric mechanisms (right hand looped arrow) at the cellular as well as the macroscopic level (bottom). Second, as there are several basic cellular electrophysiological mechanisms that precipitate the onset and maintenance of cardiac arrhythmias, mechanoelectric feedback must be included in these mechanisms (left hand looped arrow, and Fig. 2).


Figure 2
View larger version (25K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Mechanoelectric feedback and electrophysiological arrhythmic mechanisms. Centre section is a representative pair of segments in series (top normal, lower weak). The normal one shortens, producing a prolonged action potential (left hand side). The strong shortening stretches the weaker segment to shorten its action potential. The differences between the two states of repolarisation (lower left action potentials) produce electrophysiological heterogeneity/dispersion, to promote premature activation and reentry. Stretch can also produce afterdepolarisations (right hand side middle action potential) and premature beats (bottom right). Dotted lines indicates current flow between stretched and normal segments.

 

   3 Principle of mechanoelectric feedback/coupling
Top
 1 Introduction
 2 A common pathway:...
 3 Principle of mechanoelectric...
4 Which factors are...
 5 Electrophysiological...
 6 Clinical correlates, sudden...
 7 Conclusions
 References
 
Mechanoelectric transduction describes the situation in which a mechanical stimulus is transduced into an electrical signal (Fig. 1B, looped arrows in the center of heart) [8]. The physiological role of mechanoelectric feedback remains uncertain. Its arrhythmic potential has been demonstrated in cardiomyocytes, isolated ventricular muscle, isolated hearts and intact heart in situ [6,7,13]. This principle has been demonstrated in humans [12,14] and it has been suggested that it contributes to clinical arrhythmia formation [9–11]. Virtually all the anatomical subdivisions of the heart express this mechanoelectric transduction/coupling/feedback.


   4 Which factors are involved in mechanoelectric feedback?
Top
 1 Introduction
 2 A common pathway:...
 3 Principle of mechanoelectric...
 4 Which factors are...
5 Electrophysiological...
 6 Clinical correlates, sudden...
 7 Conclusions
 References
 
We have to consider mechanoelectric feedback in the light of differing clinically relevant situations. Whereas most previous studies use acute stretch, chronic stretch commonly applies to cardiomyocytes and connective tissue in intact normal or pathologic heart. Its modes of direct or indirect action could also involve apoptosis and/or remodelling. All these could affect cardiac cell electrical activity.

4.1 Mechanoelectric effects in cardiomyocytes
Firstly, in cardiomyocytes, stretch activated channels appear to be a major mechanism for acute stretch induced mechano-electric transduction, as recently reviewed by Sackin [15], Sachs [16] and Le Guennec's group [17]. Secondly, the cytoskeleton is one of the elements that plays an important role in mechano-transduction. This involves focal adhesion complexes and the extracellular matrix receptor (integrins) [18] as well as the activation of multiple co-localized enzymes (glycolytic enzymes, protein kinases, phospholipases) [19]. Thirdly, there is a form of mechano-electric coupling that involves myofibrillar proteins, sarcoplasmic reticulum and intracellular calcium changes during contraction and stretching [20–23]. Fourthly, cell death due to apoptosis mediated by angiotensin occurs several hours after stretch of the ventricular myocytes [24,25], thereby contributing to electrical heterogeneity of the myocardium and to myocardial fibrosis.

4.2 Acute stretch and fibroblasts
Kohl and co-workers [26,27] showed that cardiac fibroblasts are mechano-sensitive. Stretching of fibroblasts produce mechanically induced electrical potentials [28] that could interact with adjacent cardiomyocytes. This interaction could contribute to the dispersion of excitability and refractoriness in cardiac tissue and thus generate ectopic beats [26,27]. Therefore, the arrhythmogenic role of fibroblasts must be taken into account in clinical situations associated with remodelling and an increasing number of fibroblasts such as in chronic heart failure and the post infarcted myocardium.

4.3 Chronic stretch and cardiomyocytes
Previous investigations have mostly studied acute stretch in the intact heart. By contrast, the usual clinical situation is chronic stretch due to underlying cardiac diseases associated with cardiac overload. The common electrophysiological changes reported in experimental models of chronic cardiac overload (hypertrophic and dilated heart) are due to lengthening of the action potential [29,30]. In these states, different components of the cytoskeleton (actin filaments, microtubules and intermediate filaments) are altered profoundly [31,32]. A close relationship exists between the cytoskeleton and the regulation of transmembrane ion influx via ionic channels [19,33–35] that could contribute to early action potential lengthening in heart failure or dilated cardiomyopathy.


   5 Electrophysiological arrhythmic mechanisms and mechanoelectric feedback
Top
 1 Introduction
 2 A common pathway:...
 3 Principle of mechanoelectric...
 4 Which factors are...
 5 Electrophysiological...
6 Clinical correlates, sudden...
 7 Conclusions
 References
 
There are several electrophysiological mechanisms that promote arrhythmia formation (Fig. 1, left hand side). If mechanoelectric feedback occurs in each of them, it may be involved in generating cardiac arrhythmias (Fig. 2) [7,12].

5.1 Initiation: premature ventricular beats
5.1.1 Intracellular calcium abnormalities
Intracellular calcium exchange plays a pivotal role in the generation of cardiac arrhythmias [36–38]. Several investigations have demonstrated that mechanical alterations alter [Ca]i during diastole as well as systole [20–22]. Sustained increases in [Ca]i can produce [Ca]i oscillations that are conducive to membrane oscillations and thus result in generating premature beats and arrhythmias [38]. This favours the likelihood of arrhythmia formation induced by stretch [6]. The cytoskeleton could be an important modulator of stretch activated-calcium transients [39–41]. In chronic pathology such as heart failure and hypertrophy, calcium transients are prolonged, diastolic calcium is increased and systolic calcium reduced [42,43] thereby resulting in cardiomyocyte calcium overload [30,44,45]. Such disturbance of the cellular calcium handling favours the occurrence of delayed afterdepolarisations.

5.1.2 ‘Triggered’ activity (Fig. 2 right hand side)
Triggered afterdepolarisations are a well-recognised way of producing cardiac arrhythmias. Mechanically induced afterdepolarisations have been identified in several cardiomyocyte preparations which initiate premature beats [6–8,11]. This ‘hump’ on the action potential has been described as an early afterdepolarisation [11]. A more appropriate term might be ‘mechanically activated depolarisation’ or ‘stretch induced depolarisation’ because these mechanisms probably differ.

5.1.3 Electrophysiological heterogeneity (Fig. 2 left hand side)
Dispersion of repolarisation promotes abnormal current flow between areas of the myocardium with cells expressing different membrane potentials. This electronic flow can initiate abnormal depolarization [46], particularly in pathological states [47]. Acute sustained load shortens ventricle effective refractory periods and increases dispersion of action potential duration [48] modifying the ventricular repolarisation [6,49–52]. Chronic sustained overloaded and unloaded hearts replicate the same foetal gene expression, with prolongation of action potential duration in both cases [53]. In heart failure, the strain imposed throughout heart muscle is not homogeneous; some regions are subject to severe stress and strain while others are not [54]. This mechanical dispersion would favour the dispersion of repolarisation in the ventricles via mechanoelectric feedback. Compared with normal hearts, the failing heart is more sensitive to acute stretch; stretch shortens the ventricular refractoriness and, consequently, induces premature beats [4,5].

5.2 Sustained arrhythmia formation
Spatial electrophysiological heterogeneity is a crucial aspect of cardiac arrhythmic pathology. Re-entry is the prime mechanism promoting sustained arrhythmia, in addition to being able to initiate it. The major factors involved are reductions in conduction velocity and refractory periods along with increased excitability. It is not entirely clear whether mechanoelectric feedback promotes these types of arrhythmias.

5.2.1 Excitability
Although it has been shown that mechanical changes can induce changes in myocardial refractoriness and excitability [55–59], some studies have not upheld this thesis [4,55,60]. Apparently this depends on the location of the signal recording as represented by the heterogeneity of mechanoelectric feedback [56,57], as well as on the timing and duration of mechanical change [17,20,61]. The time that a fully activated (refractory) cell recovers full excitability is termed electrical restitution. Jalife's group [62] showed that changes in the restitution curve (supernormality and steepening) could theoretically produce a chaotic state leading to fibrillation. Mechanical load can produce analogous changes via mechanoelectric transduction or feedback [7,63] even through ischaemia flattens the curve [64]. Acute dilation of the left or right ventricle shortens local refractoriness and thus decreases the ventricular fibrillation threshold [65,66]. With chronic dilation, fibrillation threshold decreases [67] and hearts become more vulnerable to ventricular fibrillation. That is, mechanoelectrical coupling contributes to the increased susceptibility of patients with heart failure to ventricular fibrillation.

5.2.2 Conduction velocity
Load increases may reduce cardiac conduction velocity [48,68]. However, the relationship between mechanical changes and conduction velocity are not entirely clear [57,69–71]. Chronic cardiac overload is known to increase the junctional resistance between adjacent cells, thereby contributing to altered conduction in the hypertrophied myocardium [72]. Theoretical studies have shown that an increase in junctional resistance can produce discontinuous propagation [72]. Cardiac hypertrophy and heart failure modify gap junctions, the electrical connections between cells, altering their distribution and density [73]. These changes probably result in increased junctional resistance. However, the role of remodelling of gap junctions during acute and chronic stretch remains unknown, as does its role in the genesis of ventricular arrhythmias. Thus alteration in ventricular refractoriness and conduction velocity by stretching tends to decrease the myocardial wavelength. These changes and the decrease in the fibrillation threshold favour the inducibility of ventricular arrhythmias [57,65].


   6 Clinical correlates, sudden death, and mechanoelectrical feedback
Top
 1 Introduction
 2 A common pathway:...
 3 Principle of mechanoelectric...
 4 Which factors are...
 5 Electrophysiological...
 6 Clinical correlates, sudden...
7 Conclusions
 References
 
It has been recognised that a sudden sharp precordial blow can be associated with sudden death [74,75]. This can occur in the young and is often related to a sports injury [76]. In absence of contusion trauma to the heart, death is more than likely the result of a mechanically induced arrhythmia. Pathological situations appear to amplify mechanoelectric feedback [4,5,77–81] and one could predict an increased likelihood of mechanically induced arrhythmia. The following section addresses possible links between clinical correlates, arrhythmia and mechanoelectric factors. We will consider the mechanical, electrocardiographic, autonomic nervous system and electrolytic changes in turn.

6.1 Correlates involving mechanical changes
6.1.1 Dilated heart, and poor ejection fraction: intramyocardial stress and strain
Cardiac failure has been noted to be an important predisposing factor in sudden death [82]. It is arrhythmic in about half the patients in heart failure [83–85], especially in patients with NYHA class II and III. A strong relationship has been demonstrated between the prevalence of premature ventricular beats and the degree of left ventricular dilation in heart failure [86] and idiopathic dilated cardiomyopathy (Fig. 3). However, their predictive value in sudden death is low [87,89]. Moreover, their suppression by antiarrhythmic drugs does not prevent sudden death [90,91]. In contrast, left ventricular ejection fraction is a consistent predictor of sudden death in heart failure [87,89]. Peripheral vasodilators which reduce wall stress/strain have a favourable effect on cardiac arrhythmias. This include angiotensin converting enzyme (ACE) inhibitors [92,93]. A recent meta-analysis showed a significant reduction of sudden death by ACE inhibitors in patients suffering from recent myocardial infarction [93].


Figure 3
View larger version (14K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Relationships between the severity of ventricular arrhythmia, conduction abnormalities and dilatation of left ventricle in patients with idiopathic dilated cardiomyopathy (n = 186). Abbreviations: Cond defect, conduction defect; LVEDD, left ventricular end diastolic diameter (mean±S.E.); LBBBinc, incomplete left bundle branch block; LBBB, complete left bundle branch block; LAB, left anterior block; PVCs, premature ventricular contractions; Lown's grade≤2, rare and monomorphic isolated PVCs; grade 3, polymorphic PVCs; grade 4A, ventricular doublets; grade 4B, non-sustained ventricular tachycardia.

 
6.1.2 Systemic overload
Long term systemic overload, such as arterial hypertension or aortic stenosis, induces left ventricular hypertrophy that is associated with ventricular arrhythmia formation [68,94,95]. Left ventricular hypertrophy, detectable by electrocardiography or echocardiography, is a very useful index in predicting sudden death in such patients [96]. Two factors contribute to the occurrence of ventricular tachycardia: left ventricular hypertrophy decreases ventricular fibrillation threshold [97] and favours the development of cardiomyocyte afterdepolarisation [98,99] explaining, perhaps, the vulnerability to ventricular tachycardia in patients with hypertrophy [100]. For the same reasons, acute systemic overload is also arrhythmogenic, lowering the ventricular fibrillation threshold [101].

Chronic increase in load leads to hypertrophy and remodelling. Intracellular calcium, cell signals and the cytoskeleton would be involved in this process [102]. Importantly, ventricular remodelling will produce redistribution of stress and strain throughout the myocardium thereby contributing to mechanoelectrical heterogeneity. Localised stretch for 30 min can turn on early onset genes (e.g. c-myc, c-fos) and alter action potentials in the affected area [103]. Cardiovascular drugs (angiotensin converting enzyme inhibitor, carvedilol), by their antiarrhythmic action and prevention of heart remodelling, may be involved in the prevention of sudden deaths [93,104].

6.1.3 Regional ventricular stress (dyskinesia — Fig. 2)
Wall motion abnormalities which are striking in regional ischaemia can be an important contributing factor to arrhythmia formation [105,106]. Normally contracting muscle, together with rising intraventricular pressure, stretches regions of weakened muscle (Fig. 2) thereby inducing mechanically arrhythmias. The incidence of sudden death in patients with abnormal wall motion is higher than in patients without wall motion abnormalities [107]. Inhomogeneous ventricular segmental motion may even be a predictor of cardiac sudden death [108,109]. Reduction of abnormal wall motion by rapid pacing via a permanent implantable pacemaker could be used to control episodes of ventricular tachycardia [110]. In contrast, long pauses enhance wall motion abnormality, another situation often preceding arrhythmia formation.

6.2 Correlates involving ECG changes
6.2.1 QT interval and U wave
The QT interval, the T-wave [6,49–52] and the U-wave [6,111,112] of the ECG are some function of electrophysiological inhomogeneity of repolarisation that can be modulated by mechanical loading changes. U-wave changes in the epicardial ECG during load manipulation in vivo may be related to early afterdepolarisations. As such they may be involved in triggering premature ventricular contractions [113]. Dispersion of QT intervals (range of QT interval over all 12 ECG leads), a ‘spatial’ measure of ventricular repolarisation, is a controversial correlate of adverse cardiac prognosis [114–117]. Unequal distribution of stress and strain in the myocardium (regional ischaemia, remodelling) could produce altered mechanoelectric feedback and thus change ventricular electrical dispersion. Modulation of the mechanoelectrical feedback by the autonomic nervous system can also contribute to the lability of repolarisation, a predictor of arrhythmic events [118].

6.2.2 QRS complex
Intracardiac conduction defects displayed on the electrocardiogram are common in cardiac disease associated with chronic stretch of either ventricle (Fig. 3). A prolongation and dispersion of the QRS complex and late ventricular potentials due to prolongation of conduction paths in dilated ventricles implies reduced conduction velocity and predicts arrhythmic events in heart failure [117] and in idiopathic dilated cardiomyopathy [119]. For instance, after repair of tetralogy of Fallot, QRS duration correlates to chronic right ventricular volume overload, diastolic dysfunction and the risk of cardiac arrhythmias [120,121].

6.3 Correlates derived from ECG analyses
6.3.1 Heart rate variability
Early myocardial failure is associated with ventricular dilation and reduction in heart rate variability [122,123]. Alteration in autonomic tone appears to be an important consideration in this state [124,125]. It is an independent indicator of cardiac arrhythmic events in idiopathic dilated cardiomyopathy [88] and heart failure [126]. Horner et al. [127] have shown that stretching of the sinoatrial node reduces the high frequency component of heart rate variability. Chronic stretching of sinoatrial node in congestive heart failure could participate to the reduction in heart rate variability.

6.3.2 Alternans
In experimental and clinical ischaemia, electrophysiological alternans, can precede ventricular fibrillation [64,128–133]. A ventricular premature beat can turn electrical alternans either on or off [64]. In an analogous fashion, a sudden load change can turn a mechanical alternans off or on [134]. Cardiac failure and ischaemia (which also show load changes) can modulate or produce mechanical alternans [135]. Furthermore, local mechanical changes can be heterogeneous during alternans, making mechanoelectric feedback heterogeneous [136] and as result produce electrical inhomogeneity in a ventricle. Measurement of microvolt level T-wave alternans in the surface electrocardiogram is a novel and powerful way to assess the risk of ventricular arrhythmias in patients with congestive heart failure [137].

6.4 Correlates involving the autonomic nervous system
One of the few therapeutic agents that reduces the mortality of sudden (arrhythmic) cardiac death in many subsets of patients suffering from cardiac diseases is the family of β-adrenoreceptor blocking agents [138–140]. We can cautiously speculate that mechano-electric feedback interacts with the antiarrhythmic effects that β-adrenoreceptor blockers produce.

First, many of the clinical conditions associated with the autonomic nervous system dysfunction accompanying cardiac arrhythmias are associated with abnormal mechanical loads or wall motion. Secondly, sympathetic agonists or blockers may modify cardiac arrhythmia formation by affecting mechanically induced electrophysiological changes [141,142]. Pharmacological agents that possess β-blockade-like action, such as carvedilol [104] have an antiarrhythmic action, especially on sudden death associated with heart failure [143]. Following this heterogeneity theme, cardiac sympathetic efferent neuronal innervation is heterogeneous in nature [144]. It is dramatically reduced in heart failure (Fig. 4). Quantification of cardiac sympathetic efferent neuronal innervation can be useful to identify patients at risk in idiopathic dilated cardiomyopathy [145].


Figure 4
View larger version (93K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4 Anterior planar images of 123I-MIBG scintigraphy in one normal subject (left panel) and one patient suffering from heart failure with a dilated and hypertrophic heart (right panel). In the normal subject radioactive marker fixation is intense and heterogeneous (red) in the cardiac area (score heart/mediastinum=2.5). In the pathologic patient the fixation of the radioactive marker is very low (yellow and green) corresponding to a functional heart denervation (score heart/mediastinum=1.1). Abbreviations: An, anterior wall; Ap, apical wall; Bs, basal area; H, heart; Inf, inferior wall; Liv, liver; Lu, lung; M, mediastinum.

 
6.5 Correlates involving electrolyte disturbances
Hypokalaemia, can be arrhythmogenic [82,146], although interaction with other factors may be important [147]. Hypokalaemia can be related to experimental mechanotransduction [148] in which low potassium enhances mechanically induced arrhythmia in isolated perfused heart. A highly localised potassium change is also a mechanism contributing to sudden cardiac death. Extracellular potassium increases induced during acute regional ischemia [149] can be markedly reduced if the dyskinetic stretch is reduced [150].


   7 Conclusions
Top
 1 Introduction
 2 A common pathway:...
 3 Principle of mechanoelectric...
 4 Which factors are...
 5 Electrophysiological...
 6 Clinical correlates, sudden...
 7 Conclusions
References
 
Many clinical correlates with lethal cardiac arrhythmia have their origin in mechanoelectric feedback. That is, they are accompanied by mechanical changes that produce electrical changes. At one extreme, this would involved ischaemically-induced dyskinesia or infarction with ‘patchy’ mechanoelectric coupling and thus major mechanoelectric dispersion. At the other end of the spectrum, remodelling would produce less, but clinically significant, mechanoelectric dispersion. Moreover, there can be other apparently unrelated correlates such as electrolyte or autonomic neuronal imbalance. The altered stresses and strains in the myocardium would induce cardiomyocytes afterdepolarisations, electrical dispersion, changes in wavelength and re-entries: all of these effects could be involved in the genesis of cardiac arrhythmias. Mechanoelectric feedback, perhaps acting as a homeostatic feedback control, could be amplified in cardiac pathology. It is hypothetized that the common mechanoelectric feedback is a risk factor in arrhythmic death.

Time for primary review 28 days.


   Acknowledgements
 
The authors would like Dr Laurent Fauchier and Dr Danielle Casset-Senon for their help to draw Figs. 3 and 4Go.


   References
Top
 1 Introduction
 2 A common pathway:...
 3 Principle of mechanoelectric...
 4 Which factors are...
 5 Electrophysiological...
 6 Clinical correlates, sudden...
 7 Conclusions
 References
 

  1. Bayes de Luna A, Coumel P, Leclercq J.F. Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmias on the basis of data from 157 cases. Am Heart J (1989) 117:151–159.[CrossRef][Web of Science][Medline]
  2. Kürkciyan I, Meron G, Berhinger W, et al. Accuracy and impact of presumed cause in patients with cardiac arrest. Circulation (1998) 98:766–771.[Abstract/Free Full Text]
  3. Kääb S, Nuss B, Chiamvimonvat N, et al. Ionic mechanisms of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure. Circ Res (1996) 78:262–273.[Abstract/Free Full Text]
  4. Calkins H, Weisman H.F, Levine J.H, Maughan W.L, Sagawa K, Sugiura S. Effect of acute volume load on refractoriness and arrhythmia development in isolated chronically infarcted canine hearts. Circulation (1989) 79:687–697.[Abstract/Free Full Text]
  5. Wang Z, Taylor L.K, Denney W.D, Hansen D.E. Initiation of ventricular extrasystoles by myocardial stretch in chronically dilated and failing canine left ventricle. Circulation (1994) 90:2022–2031.[Abstract/Free Full Text]
  6. Lab M.J. Contraction—excitation feedback in myocardium: Physiological basis and clinical relevance. Circ Res (1982) 50:757–766.[Free Full Text]
  7. Lab M.J. Mechanoelectric feedback (transduction) in heart: concepts and implications. Cardiovasc Res (1996) 32:3–14.[Abstract/Free Full Text]
  8. Lab M.J. Mechanosensitivity as an integrative system in the heart: an audit. Prog Biophys Mol Biol (1999) 71:7–27.[CrossRef][Web of Science][Medline]
  9. Dean J.W, Lab M.J. Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology. Lancet (1989) 1:1309–1312.[Web of Science][Medline]
  10. Reiter M.J. Effects of mechano-electric feedback: potential arrhythmogenic influence in patients with congestive heart failure. Cardiovasc Res (1996) 32:44–51.[Abstract/Free Full Text]
  11. Franz M.R. Mechano-electrical feedback in ventricular myocardium. Cardiovasc Res (1996) 32:15–24.[Free Full Text]
  12. Taggart P, Sutton P.M.I. Cardiac mechano-electric feedback in man: clinical relevance. Prog Biophys Mol Biol (1999) 71:139–154.[CrossRef][Web of Science][Medline]
  13. Lab M.J. Monophasic action potentials and the detection and significance of mechanoelectric feedback in vivo. Prog Cardiovasc Dis (1991) 34:29–35.[CrossRef][Web of Science][Medline]
  14. Taggart P, Sutton P.M.I, Boyett M.R, Lab M, Swanton H. Human ventricular action-potential duration during short and long cycles — rapid modulation by ischemia. Circulation (1996) 94:2526–2534.[Abstract/Free Full Text]
  15. Sackin H. Mechanosensitive channels. Annu Rev Physiol (1995) 57:333–353.[Web of Science][Medline]
  16. Hu H, Sachs F. Stretch-activated ion channels in the heart. J Mol Cell Cardiol (1997) 29:1511–1523.[CrossRef][Web of Science][Medline]
  17. Cazorla O, Pascarel C, Brette F, Le Guennec J.Y. Modulation of ion channels and membrane receptor activity by stretch in cardiomyocytes. Possible mechanisms for mechanosensitivity. Prog Biophys Mol Biol (1999) 71:29–58.[CrossRef][Web of Science][Medline]
  18. Ingber D.E. Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol (1997) 59:575–599.[CrossRef][Web of Science][Medline]
  19. Janmey P.A. The cytoskeleton and cell signaling: component localization and mechanical transduction. Physiol Rev. (1998) 78:763–781.[Abstract/Free Full Text]
  20. Lab M.J, Allen D.G, Orchard C.H. The effects of shortening on myoplasmic calcium concentration and on the action potential in mammalian ventricular muscle. Circ Res (1984) 55:825–829.[Abstract/Free Full Text]
  21. Housemans P.K, Lee N.K, Blinks J.R. Active shortening retards the decline of the intracellular calcium transient in mammalian heart muscle. Science (1983) 22:159–161.
  22. Miura M, Boyden P.A, Ter Keurs H.E. Ca2+ waves during triggered propagated contractions in intact trabeculae. Am J Physiol (1998) 274:H266–276.[Web of Science][Medline]
  23. Calaghan S, White E. The role of calcium in the response of cardiac muscle to stretch. Prog Biophys Mol Biol (1999) 71:111–1112.
  24. Leri A, Claudio P.P, Li Q, et al. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 enhances the local renin—angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest (1998) 101:1326–1342.[Web of Science][Medline]
  25. Leri A, liu Y, Claudio P.P, et al. Insulin-like growth factor-1 induces Mdm2 and down-regulates p53, attenuating the myocyte renin—angiotensin system and stretch-mediated apoptosis. Am J Pathol (1999) 154:567–580.[Abstract/Free Full Text]
  26. Kohl P, Kamkin A.G, Kiselva I.S, Noble D. Mechanosensitive fibroblasts in the sino-atrial node region of rat heart: interaction with cardiomyocytes and possible role. Exp Physiol (1994) 79:943–956.[Abstract]
  27. Kohl P, Noble D. Mechanosensitive connective tissue: potential influence of heart rhythm. Cardiovasc Res (1996) 32:62–68.[Free Full Text]
  28. Kiselva I.S, Kamkin A.G, Kohl P, Lab M.J. Calcium and mechanically induced potentials in fibroblasts of rat atrium. Cardiovasc Res (1996) 32:98–111.[Abstract/Free Full Text]
  29. Thuringer D, Deroubaix E, Coulombe A, Coraboeuf E, Mercadier J.J. Ionic basis of the action potential prolongation in ventricular myocytes from Syrian hamsters with dilated cardiomyopathy. Cardiovasc Res (1996) 31:747–757.[Abstract/Free Full Text]
  30. Wickenden A.D, Kaprielian R, Kassiri Z, et al. The role of action potential prolongation and altered intracellular calcium handling in the pathogenesis of heart failure. Cardiovasc Res (1998) 37:312–323.[Abstract/Free Full Text]
  31. Schaper J, Froede R, Hein S, et al. Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation (1991) 83:504–514.[Abstract/Free Full Text]
  32. Hein S, Kostin S, Heling A, Maeno Y, Schaper J. The role of the cytoskeleton in heart failure. Cardiovasc Res (2000) 45:273–278.[Abstract/Free Full Text]
  33. Li Z, Burke E.P, Frank J.S, Bennett V, Philipson K.D. The cardiac Na+–Ca2+ exchanger binds to the cytoskeletal protein ankyrin. J Biol Chem (1993) 268:11489–11491.[Abstract/Free Full Text]
  34. Galli A, deFelice L.J. Inactivation of L-type Ca channels in embryonic chick ventricle cells: dependence on the cytoskeletal agents colchicine and taxol. Biophys J (1994) 67:2296–2304.[Web of Science][Medline]
  35. Yokoshiki H, Katsube Y, Sunagawa M, Seki T, Sperelakis N. Disruption of actin cytoskeleton attenuates sulfonylurea inhibition of cardiac ATP-sensitive K+ channels. Pflüger's Arch (1997) 434:203–205.[CrossRef][Web of Science][Medline]
  36. Levy M.N, Wiseman M.N. Electrophysiologic mechanisms for ventricular arrhythmias in left ventricular dysfunction: electrolytes, catecholamines and drugs. J Clin Pharmacol (1991) 31:1053–1060.[Abstract]
  37. Di Diego J.M, Antzelevitch C. High [Ca2+]o-induced electrical heterogeneity and extrasystolic activity in isolated canine ventricular epicardium. Phase 2 reentry. Circulation (1994) 89:1839–1850.[Abstract/Free Full Text]
  38. Allen D.G, Eisner D.A, Lab M.J, Orchard C.H. The effects of low sodium solutions on intracellular calcium concentrations and tension in ferret ventricular muscle. J Physiol (1984) 352:113–128.[Abstract/Free Full Text]
  39. Undrovinas A.I, Maltsev V.A. Cytochalasin D alters kinetics of Ca2+ transient in rat ventricular cardiomyocytes: an effect of altered actin cytoskeleton? J Mol Cell Cardiol (1998) 30:1665–1670.[CrossRef][Web of Science][Medline]
  40. Howarth F.C, Boyett M.R, White E. Rapid effects of Cytochalasin-D on contraction and intracellular calcium in single rat ventricular myocytes. Pfüger's Arch (1998) 436:804–806.[CrossRef][Web of Science][Medline]
  41. Wu Z, Wong K, Glogauer M, Ellen R.P, McCulloch A.G. Regulation of stretch-activated intracellular calcium transients by actin filaments. Biochem Biophys Res Commun (1999) 261:419–425.[CrossRef][Web of Science][Medline]
  42. Gomez A.M, Valvidia H.H, Cheng H, et al. Defective excitation—contraction coupling in experimental cardiac hypertrophy and heart failure. Science (1997) 276:800–806.[Abstract/Free Full Text]
  43. Vermeulen J.T. Mechanisms of arrhythmias in heart failure. J Cardiovasc Electrophysiol (1998) 9:208–221.[Web of Science][Medline]
  44. Schouten V.J.A, Vliegen H.W, van der Laarse A, Huysmans H.A. Altered calcium handling at normal contractility in hypertrophied rat heart. J Mol Cell Cardiol (1990) 22:987–998.[CrossRef][Web of Science][Medline]
  45. Balke C.W, Shorofsky S.R. Alterations in calcium handling in cardiac hypertrophy and heart failure. Cardiovasc Res (1998) 37:290–299.[Abstract/Free Full Text]
  46. Kuo C.S, Atarashi H, Reddy C.P, Surawicz B. Dispersion of ventricular repolarization and arrhythmia: study of two consecutive ventricular premature complexes. Circulation (1985) 72:370–376.[Abstract/Free Full Text]
  47. Janse M.J, van Capelle F.J, Morsink H, et al. Flow of ‘injury’ current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms. Circ Res (1980) 47:151–165.[Free Full Text]
  48. Zabel M, Portnoy S, Franz M.R. Effect of sustained load on dispersion of ventricular repolarization and conduction time in the isolated intact rabbit heart. J Cardiovasc Electrophysiol (1996) 7:9–16.[Web of Science][Medline]
  49. Lab M.J. Transient depolarisation and action potential alterations following mechanical changes in isolated myocardium. Cardiovasc Res (1980) 14:624–637.[Abstract/Free Full Text]
  50. Ford E.L, Campbell N.P. Effect of myocardial shortening velocity on duration of electrical and mechanical systole. Br Heart J (1980) 44:179–183.[Abstract/Free Full Text]
  51. Yamashita T, Inoue H, Usui M, et al. Acute effect of percutaneous transluminal mitral commissurotomy on QT interval: possible role of afterload in contraction—excitation feedback. Am Heart J (1991) 121:1634–1639.[CrossRef][Web of Science][Medline]
  52. Dean J.W, Lab M.J. Effect of changes in load on monophasic action potential and segment length of pig heart in situ. Cardiovasc Res (1989) 23:887–896.[Abstract/Free Full Text]
  53. Depre C, Shipley G.L, Chen W, et al. Unload heart in vivo replicates fetal gene expression of cardiac hypertrophy. Nat Med (1998) 4:1269–1275.[CrossRef][Web of Science][Medline]
  54. Urheim S, Edvardsen T, Torp H, Angelsen B, Smiseth O.A. Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function. Circulation (2000) 102:1158–1164.[Abstract/Free Full Text]
  55. Lerman B.B, Burkhoff D, Yue D.T, Sagawa K. Mechano-electrical feedback: Independent role of preload and contractile in modulation of canine ventricular excitability. J Clin Invest (1985) 76:1843–1850.[Web of Science][Medline]
  56. Dean J.W, Lab M.J. Regional changes in myocardial refractoriness during load manipulation in the in-situ pig heart. J Physiol (1990) 429:387–400.[Abstract/Free Full Text]
  57. Reiter M.J, Synhorst D.P, Hamm D.E. Electrophysiologic effects of acute ventricular dilatation in the isolated rabbit heart. Circ Res (1988) 62:554–562.[Abstract/Free Full Text]
  58. Halperin B.D, Adler S.W, Mann D.E, Reiter M.J. Mechanical correlates of contraction—excitation feedback during acute ventricular dilatation. Cardiovasc Res (1993) 27:1084–1087.[Abstract/Free Full Text]
  59. Hansen D.E. Mechanoelectrical feedback effects of altering preload, afterload, and ventricular shortening. Am J Physiol (1993) 264:H423–H432.[Web of Science][Medline]
  60. Calkins H, Maughan W.L, Kass D.A, Sagawa K, Levine J.H. Electrophysiological effect of volume load in isolated canine hearts. Am J Physiol (1989) 256:H1697–H1706.[Web of Science][Medline]
  61. Zabel M, Koller B.S, Sachs F, Franz M.R. Sretch-induced voltages changes in the isolated beating heart: importance of the timing of stretch and implications for stretch-activated ion channels. Cardiovasc Res (1996) 32:120–130.[Abstract/Free Full Text]
  62. Chialvo D.R, Michaels D.C, Jalife J. Supernormal excitability as a mechanism of chaotic dynamics of activation in cardiac Purkinje fibers. Circ Res (1990) 66:525–545.[Abstract/Free Full Text]
  63. Horner S.M, Dick D.J, Murphy C.F, Lab M.J. Cycle length dependence of the electrophysiological effects of increased load on the myocardium. Circulation (1996) 94:1131–1136.[Abstract/Free Full Text]
  64. Dilly S.G, Lab M.J. Electrophysiological alternans and restitution during acute regional ischaemia in myocardium of anaesthetized pig. J Physiol (Lond) (1988) 402:315–333.[Abstract/Free Full Text]
  65. Jalal S, Williams G.R, Mann D.E, Reiter M.J. Effect of acute ventricular dilatation on fibrillation thresholds in the isolated rabbit heart. Am J Physiol (1992) 263:H1306–H1310.[Web of Science][Medline]
  66. Burton F.L, Cobbe S.M. Effect of sustained stretch on dispersion of ventricular fibrillation intervals in normal rabbit hearts. Cardiovasc Res (1998) 39:351–359.[Abstract/Free Full Text]
  67. Rosen S, Lahorra M, Cohen M.V, Buttrick P. Ventricular fibrillation threshold is influenced by left ventricular stretch and mass in the absence of ischaemia. Cardiovasc Res (1991) 25:458–462.[Abstract/Free Full Text]
  68. Sideris D.A. High blood pressure and ventricular arrhythmias. Eur Heart J (1993) 14:1548–1553.[Abstract/Free Full Text]
  69. Dominguez G, Fozzard H. Effect of stretch on conduction velocity and cable properties of cardiac purkinje fibers. Am J Physiol (1979) 237:C119–C124.[Web of Science][Medline]
  70. Reiter M.J, Zetelaki Z, Kirchhof C.J.H, Boersma L, Allessie M.A. Interaction of acute ventricular dilatation and d-sotalol during sustained reentrant ventricular tachycardia around a fixed obstacle. Circulation (1994) 89:423–431.[Abstract/Free Full Text]
  71. Zhu W.X, Johnson S.B, Brandt R, Burnett J, Packer D.L. Impact of volume loading and load reduction on ventricular refractoriness and conduction properties in canine congestive heart failure. J Am Coll Cardiol (1997) 30:825–833.[Abstract]
  72. Cooklin M, Wallis W.R.J, Sheridan D.J, Fry C.H. Changes in cell-to-cell electrical coupling associated with left ventricular hypertrophy. Circ Res (1997) 80:765–771.[Abstract/Free Full Text]
  73. Peters N.S, Green C.R, Poole-Wilson P.A, Severs N.J. Reduced content of Connexin43 gap junctions in ventricular myocardium from hypertrophied and ischemic human hearts. Circulation (1993) 88:864–875.[Abstract/Free Full Text]
  74. Kohl P, Hunter P, Noble D. Stretch-induced changes in heart rate and rhythm: clinical observations, experiments and mathematical models. Prog Biophys Mol Biol (1999) 71:91–138.[CrossRef][Web of Science][Medline]
  75. Khol P, Nesbitt A.D, Cooper P.J, Lei M. Sudden death by commotio cordis: role of mechano-electric feedback. Cardiovasc Res (2001) 50:280–289.[Abstract/Free Full Text]
  76. Maron B.J, Poliac L.C, Kaplan J.A, Mueller F.O. Blunt impact to the chest leading to sudden cardiac death from cardiac arrest during sports activities. New Engl J Med (1995) 33:337–342.
  77. Tobler H.G, Gornic C.C, Anderson R.W, Benditt D.G. Electrophysiologic properties of the myocardial infarction border zone: Effects of transient aortic occlusion. Surgery (1986) 100:150–156.[Web of Science][Medline]
  78. Zhou B.Y, Harrison F.G, Dick D.J, Horner S.M, Murphy C.F, Lab M.J. Ventricular arrhythmogenesis is enhanced by mechanelectric feedback in regional ischaemic heart of the anaesthetised pig. J Physiol (Lond) (1993) 473:184P.
  79. Lab M.J, Zhou B.Y, Dick D.J, Horner S.M, Murphy C.F, Harrison F.G. Stretch-induced ventricular fibrillation in normal and globally anoxic isolated guinea pig hearts. J Physiol (Lond) (1993) 473:183P.
  80. Pye M.P, Cobbe S.M. Arrhythmogenesis in experimental models of heart failure: the role of increased load. Cardiovasc Res (1996) 32:248–257.[Abstract/Free Full Text]
  81. Horner S.M, Lab M.J, Murphy C.F, Dick D.J, Zhou B, Harrison F.G. Mechanically induced changes in action potential duration and left ventricular segment length in acute regional ischaemia in the in situ porcine heart. Cardiovasc Res (1994) 28:528–534.[Abstract/Free Full Text]
  82. Packer M, Gottlieb S.S, Blum M.A. Immediate and long-term pathophysiologic mechanisms underlying the genesis of sudden cardiac death in patients with congestive heart failure. Am J Med (1987) 82:4–10.[Web of Science][Medline]
  83. Packer M. Sudden unexpected death in patients with congestive heart failure: A second frontier. Circulation (1985) 72:681–687.[Free Full Text]
  84. Kjekshus J. Arrhythmias and mortality in congestive heart failure. Am J Cardiol (1990) 65:42I–48I.[Medline]
  85. Simon S.R, Powell L.H, Bartzokis T.C, Hoch D.H. A new system for classification of cardiac death as arrhythmic, ischemic, or due to myocardial pump failure. Am J Cardiol (1995) 76:896–898.[CrossRef][Web of Science][Medline]
  86. Koilpillai C, Quinones M.A, Greenberg B, et al. Relation of ventricular size and function to heart failure status and ventricular dysrythmias in patients with severe left ventricular dysfunction. Am J Cardiol (1996) 77:606–611.[CrossRef][Web of Science][Medline]
  87. Teerlink J.R, Jaladuluddin M, Anderson S, et al. Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. Circulation (2000) 101:40–46.[Abstract/Free Full Text]
  88. Fauchier L, Babuty D, Cosnay P, Fauchier J.P. Prognostic value of heart rate variability for sudden death and major arrhythmic events in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol (1999) 33:1203–1207.[Abstract/Free Full Text]
  89. Cosnay P, Fauchier L, Babuty D, et al. Fighting sudden death: a worldwide challenge. Aliot E, Clementy J, Prystowsky E.N, eds. (2000) Armonk, NY: Futura. 343–359.
  90. Flaker G.C, Blackshear J.C, McBride R, et al. Antiarrhythmic drug and cardiac mortality in atrial fibrillation. J Am Coll Cardiol (1992) 20:527–532.[Abstract]
  91. Singh S.N. Congestive heart failure and arrhythmias: therapeutic modalities. J Cardiovasc Electrophysiol (1997) 8:89–97.[Web of Science][Medline]
  92. Cohn J.N, Archibald D.G, Phil M, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration cooperative study. New Engl J Med (1986) 314:1547–1552.[Abstract]
  93. Domanski M.J, Exner D.V, Borkowf C.B, et al. Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. J Am Coll Cardiol (1999) 33:598–604.[Abstract/Free Full Text]
  94. McLenachan J.M, Henderson E, Morris K.I, Dargie H.J. Ventricular arrhythmias in patients with hypertensive left ventricular hypertrophy. New Engl J Med (1987) 317:787–792.[Abstract]
  95. Sorgato A, Faggiano P, Aurigemma G.P, Rusconi C, Gaasch W.H. Ventricular arrhythmias in adult aortic stenosis: prevalence, mechanisms, and clinical relevance. Chest (1998) 113:482–491.[CrossRef][Web of Science][Medline]
  96. Pearson A.C, Pasierski T, Labovitz A. Left ventricular hypertrophy: diagnosis, prognosis, and management. Am Heart J (1991) 121:148–157.[CrossRef][Web of Science][Medline]
  97. Versailles J.T, Verscheure Y, Le Kim A, Pourrias B. Comparison between the ventricular fibrillation thresholds of spontaneously hypertensive and normotensive rats: investigation of antidysrhythmic drugs. J Cardiovasc Pharmacol (1982) 4:430–435.[Web of Science][Medline]
  98. Aronson R.S. Afterpotentials and triggered activity in hypertrophied myocardium from rats with renal hypertension. Circ Res (1981) 48:720–727.[Abstract/Free Full Text]
  99. de Groot S.H.M, Schoenmakers M, Molenschot M.M.C, Leunissen J.D.M, Wellens H.J.J, Vos M.A. Contractile adaptations preserving cardiac output predispose the hypertrophied canine heart to delayed afterdepolarization-dependent ventricular arrhythmias. Circulation (2000) 102:2145–2151.[Abstract/Free Full Text]
  100. Anderson K.P, Stinson E.B, Derby G.C, Oyer P.E, Mason J.W. Vulnerability of patients with obstructive hypertrophic cardiomyopathy to ventricular arrhythmia induction in the operating room: analysis of 17 patients. Am J Cardiol (1983) 51:811–816.[CrossRef][Web of Science][Medline]
  101. Blatt C.M, Verrier R.L, Lown B. Acute blood pressure elevation and ventricular fibrillation threshold during coronary occlusion and reperfusion in the dog. Am J Cardiol (1977) 39:523–528.[CrossRef][Web of Science][Medline]
  102. Bustamante J.O, Ruknudin A, Sachs F. Stretch-activated channels in heart cells: relevance to cardiac hypertrophy. J Cardiovasc Pharmacol (1991) 17:S110–S113.[CrossRef][Web of Science][Medline]
  103. Meghji P, Nazir S.A, Dick D.J, Bailey M.E.S, Johson K, Lab M.J. Regional worload induced changes in electrophysiology and immediate early gene expression in intact in situ porcine heart. J Mol Cell Cardiol (1997) 29:3147–3155.[CrossRef][Web of Science][Medline]
  104. Feuerstein G.Z, Bril A, Ruffolo R.R. Protective effects of carvedilol in the myocardium. Am J Cardiol (1997) 80:41L–45L.[CrossRef][Medline]
  105. Califf R.M, Burks J.M, Behar V.S, Margolis J.R, Wagner G.S. Relationships among ventricular arrhythmias, coronary artery disease, and angiographic and electrocardiographic indicators of myocardial fibrosis. Circulation (1978) 57:725–732.[Abstract/Free Full Text]
  106. Siogas K, Pappas S, Graekas G, Goudevenos J, Liapi G, Sideris D.A. Segmental wall motion abnormalities alter vulnerability to ventricular ectopic beats associated with acute increases in aortic pressure in patients with underlying coronary artery disease. Heart (1998) 79:268–273.[Abstract/Free Full Text]
  107. Shen W.F, Cui L.Q, Wang M.H, Gong L.S, Lesbre J.P. Spontaneous alterations in left ventricular regional wall motion after acute myocardial infarction. Chin Med J (Engl Ed) (1990) 103:1015–1018.
  108. Weaver W.D, Lorch G.S, Alvarez H.A, Cobb L.A. Angiographic finding and prognostic indicators in patients resuscitated from sudden cardiac death. Circulation (1976) 54:895–900.[Abstract/Free Full Text]
  109. Califf R.M, McKinnis R.A, Burks J, et al. Prognostic implications of ventricular arrhythmias during 24 h ambulatory monitoring in patients undergoing cardiac catheterization for coronary artery disease. Am J Cardiol (1982) 50:23–31.[CrossRef][Web of Science][Medline]
  110. Perticone F, Ceravolo R, Maio R, Cosco C, Giancotti F, Mattioli P.L. Mechano-electric feedback and ventricular arrhythmias in heart failure. The possible role of permanent cardiac stimulation in preventing ventricular tachycardia. Cardiologia (1993) 38:247–252.[Medline]
  111. el Sherif N, Zeiler R.H, Craelius W, Gough W.B, Henkin R. QTU prolongation and polymorphic ventricular tachyarrhythmias due to bradycardia-dependent early afterdepolarizations. Afterdepolarizations and ventricular arrhythmias. Circ Res (1988) 63:286–305.[Abstract/Free Full Text]
  112. Choo M.C, Gibson D.G. U-Waves in ventricular hypertrophy: possible demonstration of mechano-electric feedback. Br Heart J (1986) 55:428–433.[Abstract/Free Full Text]
  113. Franz M.R, Burkhoff D, Yue D.T, Sagawa K. Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts. Cardiovasc Res (1989) 23:213–223.[Abstract/Free Full Text]
  114. Higham P.D, Campbell R.W. QT dispersion. Br Heart J (1994) 71:508–510.[Free Full Text]
  115. Okin P.M, Devereux R.B, Howard B.V, Fabsitz R.R, Lee E.T, Welty T.K. Assessment of QT interval and QT dispersion for prediction of all-cause and cardiovascular mortality in American Indians. The strong heart study. Circulation (2000) 101:61–66.[Abstract/Free Full Text]
  116. Galinier M, Vialette J.C, Fourcade J, et al. QT interval dispersion as a predictor of arrhythmic events in congestive heart failure. Eur Heart J (1998) 19:1054–1062.[Abstract/Free Full Text]
  117. Anastasiou-Nana M.I, Nanas J.N, Karagounis L.A, et al. Relation of dispersion of QRS and QT in patients with advanced congestive heart failure to cardiac and sudden death mortality. Am J Cardiol (2000) 85:1212–1217.[CrossRef][Web of Science][Medline]
  118. Atiga W.L, Calkins H, Lawrence J.H, Tomaselli G.F, Smith J.M, Berger R.D. Beat-to-beat repolarization lability identifies patients at risk for sudden cardiac death. J Cardiovasc Electrophysiol (1998) 9:899–908.[Web of Science][Medline]
  119. Fauchier L, Babuty D, Cosnay P, Poret Ph, Rouesnel Ph, Fauchier J.P. Long-term prognostic of time domain analysis of signal averaged electrocardiography in idiopathic dilated cardiomyopathy. Am J Cardiol (2000) 85:618–623.[CrossRef][Web of Science][Medline]
  120. Gatzoulis M.A, Till J.A, Somerville J, Redington A.N. Mechanoelectrical interaction in tetralogy of Fallot. QRS prolongation relates to right ventricular size and predicts malignant ventricular arrhythmias and sudden death. Circulation (1995) 92:231–237.[Abstract/Free Full Text]
  121. Dreyer W.J, Paridon S.M, Fisher D.J, Garson A. Rapid ventricular pacing in dogs with right ventricular outflow tract obstruction: insights into a mechanism of sudden death in postoperative tetralogy of Fallot. J Am Coll Cardiol (1993) 21:1731–1737.[Abstract]
  122. Fauchier L, Babuty D, Cosnay P, Autret M.L, Fauchier J.P. Heart rate variability in idiopathic dilated cardiomyopathy: characteristics and prognostic value. J Am Coll Cardiol (1997) 30:1009–1014.[Abstract]
  123. Zbilut J.P, Lawson L. Decreased heart rate variability in significant cardiac events. Crit Care Med (1988) 16:64–66.[Web of Science][Medline]
  124. Casolo G, Balli E, Taddei T, Amuhasi J, Gori C. Decreased spontaneous heart rate variability in congestive heart failure. Am J Cardiol (1989) 64:1162–1167.[CrossRef][Web of Science][Medline]
  125. Stein P.K, Freedland K.E, Skala J.A, et al. Heart rate variability is independent of age, gender, and race in congestive heart failure with a recent acute exacerbation. Am J Cardiol (1997) 79:511–512.[CrossRef][Web of Science][Medline]
  126. Galinier M, Pathak A, Fourcade J, et al. Depressed low frequency power of heart rate variability as independent predictor of sudden death in chronic heart failure. Eur Heart J (2000) 21:475–482.[Abstract/Free Full Text]
  127. Horner S.M, Murphy C.F, Coen B, et al. Contribution to heart rate variability by mechanoelectric feedback. Stretch of the sinoatrial node reduces heart rate variability. Circulation (1996) 7:1762–1767.
  128. Hellerstein H.K, Liebow I.M. Electrical alternans in experimental coronary artery occlusion. Am J Physiol (1950) 160:366–374.[Free Full Text]
  129. Abe S, Nagamoto Y, Fukuchi Y, Hayakawa T, Kuroiwa A. Relationship of alternans of monophasic action potential and conduction delay inside the ischemic border zone to serious ventricular arrhythmia during acute myocardial ischemia in dogs. Am Heart J (1989) 117:1223–1233.[CrossRef][Web of Science][Medline]
  130. Salerno J.A, Previtali M, Panciroli C, et al. Ventricular arrhythmias during acute myocardial ischaemia in man. The role and significance of R-ST-T alternans and the prevention of ischaemic sudden death by medical treatment. Eur Heart J (1986) 7(Suppl_A):63–75.
  131. Smith J.M, Clancy E.A, Valeri C.R, Ruskin J.N, Cohen R.J. Electrical alternans and cardiac electrical instability. Circulation (1988) 77:110–121.[Abstract/Free Full Text]
  132. Rozanski G.J, Jalife J, Moe G.K. Reflected reentry in nonhomogeneous ventricular muscle as a mechanism of cardiac arrhythmias. Circulation (1984) 69:163–173.[Abstract/Free Full Text]
  133. Rosenbaum D.S, Jackson L.E, Smith J.M, Garan H, Ruskin J.N, Cohen R.J. Electrical alternans and vulnerability to ventricular arrhythmias. New Engl J Med (1994) 330:235–241.[Abstract/Free Full Text]
  134. Murphy C.F, Lab M.J, Horner S.M, Dick D.J, Harrison F.G. Load induced period doubling bifurcations in the anaesthetised pig heart. Chaos Solitons Fractals (1995) 5:707–712.[CrossRef][Web of Science]
  135. Hess O.M, Surber E.P, Ritter M, Krayenbuehl H.P. Pulsus alternans: its influence on systolic and diastolic function in aortic valve disease. J Am Coll Cardiol (1984) 4:1–7.[Abstract]
  136. Murphy C.F, Lab M.J, Horner S.M, Dick D.J, Harrison F.G. Regional electromechanical alternans in anesthetized pig hearts: modulation by mechanoelectric feedback. Am J Physiol (1994) 267:H1726–1735.[Web of Science][Medline]
  137. Klingenheben T, Zabel M, D'Agostino R.B, Cohen R.J, Hohnloser S.H. Predictive value of T-wave alternans for arrhythmic events in patients with congestive heart failure. Lancet (2000) 356:651–652.[CrossRef][Web of Science][Medline]
  138. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet (1999) 353:2001–2007.[CrossRef][Web of Science][Medline]
  139. CIBIS-II Investigators and Committees. The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet (1999) 353:9–13.[CrossRef][Web of Science][Medline]
  140. Andresen D, Ehlers H.C, Wiedeman M, Brüggemann T. Beta blockers: evidence versus wishful thinking. Am J Cardiol (1999) 83:64D–67D.[Web of Science][Medline]
  141. Horner S.M, Murphy C.F, Coen B, Dick D.J, Lab M.J. Sympathomimetic modulation of load-dependent changes in the action potential duration in the in situ porcine heart. Cardiovasc Res (1996) 32:148–157.[Abstract/Free Full Text]
  142. Lab M.J, Dick D, Harrison F.G. Propranolol reduces stretch arrhythmia in isolated rabbit heart. J Physiol (Lond) (1992) 446:539P.
  143. Australia/New Zealand Heart Failure Research Collaborative Group. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Lancet (1997) 349:375–380.[CrossRef][Web of Science][Medline]
  144. Hainsworth R. Reflexes from the heart. Physiol Rev (1991) 71:617–658.[Free Full Text]
  145. Merlet P, Benvenuti C, Moyse D, et al. Prognostic value of MIBG imaging in idiopathic dilated cardiomyopathy. J Nucl Med (1999) 40:917–923.[Abstract/Free Full Text]
  146. Podrid P.J. Potassium and ventricular arrhythmias. Am J Cardiol (1990) 65:33E–44E.[CrossRef][Medline]
  147. Dargie H.J, Cleland J.G, Leckie B.J, Inglis C.G, East B.W, Ford I. Relation of arrhythmias and electrolyte abnormalities to survival in patients with severe chronic heart failure. Circulation (1987) 75:IV98–IV107.[Medline]
  148. Evans S.J, Levi A.J, Jones J.V. Wall stress induced arrhythmia is enhanced by low potassium and early left ventricular hypertrophy in the working rat heart. Cardiovasc Res (1995) 29:555–562.[Abstract/Free Full Text]
  149. Hill J.L, Gettes L.S. Effect of acute coronary artery occlusion on local myocardial extracellular K+ activity in swine. Circulation (1980) 61:768–778.[Abstract/Free Full Text]
  150. Nazir S.A, Dick D, Lab M.J. Proceedings of the international meeting on mechanoelectric feedback, Trento, Italy. (1997).

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



This Article
Right arrow Extract 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 Babuty, D.
Right arrow Articles by Lab, M. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Babuty, D.
Right arrow Articles by Lab, M. J
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?