Localized injury in cardiomyocyte network: a new experimental model of ischemia-reperfusion arrhythmias

Arutunyan, Ara; Webster, Daniel R.; Swift, Luther; Sarvazyan, Narine

doi:10.1152/ajpheart.2001.280.4.h1905

Cited by 45 publications

(63 citation statements)

References 39 publications

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“…Geometrically well-defined regions of heterogeneity can be achieved in cell cultures by restricting cell access to the bath by a glass coverslip (20) but are not easily reversed. Several groups have developed flow chambers that can selectively and reversibly superfuse a given area of a cell monolayer with drug (2,14,17,21). However, none of the designs resulted in the creation of a sharply defined, scalable island with uniform properties distinct from the remainder of the monolayer that would be valuable in the study of the initiation or maintenance of reentry.…”

Section: Discussionmentioning

confidence: 99%

Region of slowed conduction acts as core for spiral wave reentry in cardiac cell monolayers

Lin¹,

Garber

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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in cardiac tissue is related to the occurrence of arrhythmias. Of importance are regions of slowed conduction, which have been implicated in the formation of conduction block and reentry. Experimentally, it has been a challenge to produce local heterogeneity in a manner that is both reversible and well controlled. Consequently, we developed a dual-zone superfusion chamber that can dynamically create a small (5 mm) central island of heterogeneity in cultured cardiac cell monolayers. Three different conditions were studied to explore the effect of regionally slowed conduction on wave propagation and reentry: depolarization by elevated extracellular potassium, sodium channel inhibition with lidocaine, and cell-cell decoupling with palmitoleic acid. Using optical mapping of transmembrane voltage, we found that the central region of slowed conduction always served as the core region around which a spiral wave formed and then revolved following a period of rapid pacing. Because of the localized slowing in the core region, we observed experimentally for the first time an S shape of the spiral wave front near its tip. These results indicate that a small region of slowed conduction can play a crucial role in the formation, anchoring, and modulation of reentrant spiral waves.

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Section: Discussionmentioning

confidence: 99%

Region of slowed conduction acts as core for spiral wave reentry in cardiac cell monolayers

Lin¹,

Garber

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Others have recorded from ICC that grew out of small tissue explants (14) or from ICC identified in intact tissues (6,30,46). Our approach may enable studies that have not been possible with currently available techniques, such as the effects of network size on slow-wave amplitude (16,29), the role of network expansion in the normal development and maturation of the GI pacemaker apparatus (39,43), the mechanisms of pacemaker integration in ICC networks (15,24,30,46), the mechanisms of arrhythmias caused by focal damages in the ICC networks (24,26,1), and the modulatory effects of electrically coupled smooth muscle cells on electrical pacemaking.…”

Section: Resultsmentioning

confidence: 99%

Immunomagnetic enrichment of interstitial cells of Cajal

Ördög

Redelman

Horowitz

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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ruptions of networks of interstitial cells of Cajal (ICC), gastrointestinal pacemakers and mediators of neurotransmission, can lead to disordered phasic contractions and peristalsis by reducing and uncoupling electrical slow waves. However, detailed analysis of the ICC network behavior has been hampered by their scarcity, limited accessibility in intact tissues, and contamination with other cell types in culture. Our goal was to develop a simple technique to purify ICC from murine gastrointestinal muscles for functional studies. We identified ICC in live small intestinal muscles or primary cell cultures by Kit immunoreactivity using fluorescent antibodies. Because this technique also labels resident macrophages nonspecifically, parallel studies were performed in which nonfluorescent Kit antibodies and macrophages labeled with fluorescent dextran were used for subtractive analysis of ICC. In both groups, Kit-positive cells were tagged with superparamagnetic antibodies and sorted on magnetic columns. Efficacy was assessed by flow cytometry. ICC enrichment from primary cultures and freshly dissociated tissues was ϳ63-fold and ϳ8-fold, respectively. Unlike the cells derived directly from tissues, cells sorted from cultures frequently yielded extensive, nearly homogenous ICC networks on reseeding. Monitoring oscillations in mitochondrial Ca 2ϩ or membrane potential by imaging revealed spontaneous rhythmicity in these networks. Cells that did not bind to the columns yielded cultures that were depleted of ICC and dominated by smooth muscle cells. In conclusion, immunomagnetic sorting of primary cultures of ICC results in relatively homogenous, functional ICC networks. This technique is less suitable for obtaining ICC from freshly dispersed cells. mouse; Kit; macrophage; pacemaking; fluorescent imaging INTERSTITIAL CELLS OF CAJAL (ICC) are specialized mesenchymal cells located within the tunica muscularis of the gastrointestinal (GI) tract that play critical roles in GI motor functions and their regulation (32). Multipolar ICC, which form two-dimensional networks in the myenteric region, on the submucosal border of the circular smooth muscle layer, and within intermuscular septa of phasic GI smooth muscles, play an essential role in phasic contractile activity and peristalsis by generating and propagating electrical slow waves (4,6,12,13,24,26, 42). Elongated or bipolar ICC, which are more loosely distributed within bundles of smooth muscle cells (where they form close contacts with varicose processes of enteric motor neurons), mediate excitatory and inhibitory neural inputs to the smooth musculature (45), may amplify slow waves (5), and contribute to vagally mediated mechanoreception (9).The discovery that ICC can be identified by expression of the receptor tyrosine kinase Kit [stem cell factor (SCF) receptor, CD117] (13, 21, 39, 42) has led to several studies on the morphology of ICC networks in human GI disorders. Damages to ICC networks have been described in congenital and acquired GI disorders including anorectal ...

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“…The latter were prepared from 1-2 day-old Sprague-Dawley rats, as described previously. 10 After 18 hours of co-culture, the medium was changed twice to remove unattached cells. Fluorescence was acquired from five random areas of each coverslip using Zeiss LSM512 confocal imaging system.…”

Section: Methodsmentioning

confidence: 99%

Effects of N-cadherin overexpression on the adhesion properties of embryonic stem cells

Karabekian

Gillum

Wong

et al. 2009

Cell Adhesion & Migration

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Constitutive overexpression of N-cadherin in mouse embryonic stem cells led to marked changes in the phenotype and adhesion properties of these cells. The changes included the formation of smaller embryonic bodies, elevated mRNA and total protein levels of N-cadherin, and increased amounts of p120 catenin and connexin-43. N-cadherin cells exhibited decreased attachment to non-cell surfaces, while their adhesiveness to each other and to rat neonatal cardiomyocytes was significantly elevated. The findings suggest that N-cadherin overexpression can facilitate electromechanical integration of stem cells into excitable tissues with endogenously high levels of N-cadherin, such as the heart and brain.

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Localized injury in cardiomyocyte network: a new experimental model of ischemia-reperfusion arrhythmias

Cited by 45 publications

References 39 publications

Region of slowed conduction acts as core for spiral wave reentry in cardiac cell monolayers

Region of slowed conduction acts as core for spiral wave reentry in cardiac cell monolayers

Immunomagnetic enrichment of interstitial cells of Cajal

Effects of N-cadherin overexpression on the adhesion properties of embryonic stem cells

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