Electrical coupling of cardiomyocyte sheets occurs rapidly via functional gap junction formation

Haraguchi, Yuji; Shimizu, Tatsuya; Yamato, Masayuki; Kikuchi, Akihiko; Okano, Teruo

doi:10.1016/j.biomaterials.2006.04.034

Cited by 168 publications

(129 citation statements)

References 36 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…However, the effects we report reached steady state in 10 min, which is faster than the time course of G j remodeling reported in acute ischemia (5). This time course may also be shorter than the time required for new G j formation (20), especially in intact tissue. Finally, cardiac conduction may involve alternative modes of intercellular coupling that are not exclusively dependent on gap junctions (25,37).…”

Section: The -V Is Relationshipcontrasting

confidence: 44%

Interstitial volume modulates the conduction velocity-gap junction relationship

Veeraraghavan

Salama

Poelzing

2012

American Journal of Physiology-Heart and Circulatory Physiology

126

View full text Add to dashboard Cite

Cardiac conduction through gap junctions is an important determinant of arrhythmia susceptibility. Yet, the relationship between degrees of Gj uncoupling and conduction velocity (θ) remains controversial. Conflicting results in similar experiments are normally attributed to experimental differences. We hypothesized that interstitial volume modulates conduction velocity and its dependence on Gj. Interstitial volume (VIS) was quantified histologically from guinea pig right ventricle. Optical mapping was used to quantify conduction velocity and anisotropy (ARθ). Albumin (4 g/l) decreased histologically assessed VIS, increased transverse θ by 71 ± 10%, and lowered ARθ. Furthermore, albumin did not change isolated cell size. Conversely, mannitol increased VIS, decreased transverse θ by 24 ± 4%, and increased ARθ. Mannitol also decreased cell width by 12%. Furthermore, mannitol was associated with spontaneous ventricular tachycardias in three of eight animals relative to zero of 15 during control. The θ-Gj relationship was assessed using the Gj uncoupler carbenoxolone (CBX). Whereas 13 μM CBX did not significantly affect θ during control, it slowed transverse θ by 38 ± 9% during mannitol (edema). These data suggest changes in VIS modulate θ, ARθ, and the θ-Gj relationship and thereby alter arrhythmia susceptibility. Therefore, VIS may underlie arrhythmia susceptibility, particularly in diseases associated with gap junction remodeling.

show abstract

Section: The -V Is Relationshipcontrasting

confidence: 44%

Interstitial volume modulates the conduction velocity-gap junction relationship

Veeraraghavan

Salama

Poelzing

2012

American Journal of Physiology-Heart and Circulatory Physiology

126

View full text Add to dashboard Cite

show abstract

“…52 With the caveat that these approaches may be restricted to open-chest procedures, they could have the advantage not only to improve graft viability through maintenance of intercellular connections and survival signals originating from the extracellular matrix, but also to reduce the risk of arrhythmias through appropriate coupling of cells between them within the sheet 53 and with those of the underlying host myocardium. 54 Future clinical trials should correct for the baseline arrhythmic risk and thus allow to more clearly identify the risk directly attributable to stem cell therapy, taking into account not only the nature of the cells, but also the myocardial microenvironment and the extent of inflammatory damage triggered by cell transfer.…”

Section: Improved Methods Of Cell Deliverymentioning

confidence: 99%

Stem Cell Therapy for Heart Failure

Menasché

2009

Circulation

109

View full text Add to dashboard Cite

Abstract-So far, the major safety issue raised by the use of stem cells for cardiac repair has been the occurrence of ventricular arrhythmias, particularly after skeletal myoblast transplantation. Although one cannot refute a potential intrinsic arrhythmogenicity of stem cells, primarily related to their common lack of electromechanical integration into the recipient myocardium, it is also important to recognize that patients eligible for cell replacement therapy are prone to develop arrhythmias because of their underlying ischemic heart disease. Another confounding factor is the method used for the intramyocardial delivery of the cells, which can cause enough inflammatory tissue damage to further increase ventricular irritability on top of an already high baseline level. Thus any strategy designed to minimize the risk of stem cell-associated ventricular arrhythmias should take into account, besides the cell-specific ability to appropriately couple with host cardiomyocytes, the method of cell transfer and the nature of the myocardial environment targeted for cell engraftment. A more accurate characterization of the baseline risk of arrhythmias in these patients would thus be helpful for better assessing the respective contribution of the donor cells and the host myocardium to these complications. The risk-to-benefit ratio of stem cell therapy will finally have to be revisited in light of the fact that because this baseline risk is usually high, most of these patients will in any way be fitted with an implantable defibrillator. Key Words: arrhythmia Ⅲ cells Ⅲ heart failure Ⅲ myocardial infarction Ⅲ stem cells T he clinical acceptance of any new therapy is largely based on the risk-to-benefit ratio. In the case of stem cell treatment for chronic heart failure, the clinical results have so far been marginally successful, when not negative, whereas the concern that intramyocardial delivery of cells, particularly skeletal myoblasts, could cause potentially life-threatening ventricular arrhythmias has been repeatedly raised. However, in this specific context of heart failure, the legitimate emphasis on this safety issue may have led to somewhat underscore the fact that most of the patients eligible for cell replacement therapy are at high risk of arrhythmias because of their underlying ischemic heart disease to such an extent that they are now increasingly fitted with internal cardioverterdefibrillators (ICDs). 1 The objective of the present article is thus to highlight the fact that the proarrhythmic risk of stem cell therapy may not be entirely related to the cells themselves and to show that at least 2 other factors (ie, the mode of their delivery and the nature of the target substrate) can also be important contributors to posttransplantation arrhythmias. These factors should definitely be taken into account by any strategy aimed at reducing the arrhythmic risk of stem cell therapy. Summary of Experimental Data on StemCell-Induced ArrhythmiasBasically, there are 3 major mechanisms that can cause arrhythmias: reent...

show abstract

“…Within layered cardiac constructs, gap junctions are formed which rapidly establish an electrical connection between the cell sheets, leading to 3D cardiac tissues that synchronously pulsatile [7]. Additionally, when these tissues were transplanted onto the subcutaneous tissue of nude rats, the grafts were macroscopically observed to beat synchronously [8].…”

Section: Cardiac Tissue Reconstructionmentioning

confidence: 99%