Cardiac arrhythmias arise from abnormalities of either impulse propagation (reentry-based) or impulse initiation (focal or ectopic). The development of reentry arrhythmias, which involves rotation of an excitation wave around an anatomical or functional block, was observed both in vitro and in vivo and conceptually is well understood. In contrast, our comprehension of ectopic (non-reentrant) arrhythmias has a major gap. To gain initial insights into this process we propose to use a range of available models of cardiac tissue (both experimental and theoretical) in which infarct-like area will be created. Our preliminary studies have revealed that development of ectopic arrhythmias proceeds via an essential step, which we named an ectopic nexus (EN) It refers to a functional state of an injured cardiac tissue in which multiple poorly-coupled ectopic sources form a transient """"""""breeding"""""""" microenvironment in which ectopic activity develops from individual cells into slowly propagating ectopic waves confined to the area of injury. The waves of excitation from surrounding healthy tissue fail to invade the EN, allowing slow ectopic waves to co-exist side-by-side with normal propagation pattern. Subsequent relief of EN conditions results in an escape of the ectopic waves leading to an arrhythmia. The EN is a novel concept, which, if it does occur in vivo, has important implications for both understanding and clinical treatment of arrhythmias and ventricular fibrillation. However, experimental and theoretical models employed in our previous studies had several limitations and the relevance of the EN concept to in vivo arrhythmias needs to be further established. Specifically, one needs to know whether EN is limited to 2D cultures of cardiac cells or to a specific set of experimental conditions, how electrical activity match data obtained using calcium transients, whether the EN occurs in a 3D environment, and many other questions. The goal of this application is to provide answers to these questions in order to establish a pathophysiological significance of EN. ? ?
| Karabekian, Zaruhi; Posnack, Nikki Gillum; Sarvazyan, Narine (2011) Immunological barriers to stem-cell based cardiac repair. Stem Cell Rev 7:315-25 |
| Posnack, Nikki Gillum; Lee, Norman H; Brown, Ronald et al. (2011) Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity. Toxicology 279:54-64 |
| Biktashev, Vadim N; Biktasheva, Irina V; Sarvazyan, Narine A (2011) Evolution of spiral and scroll waves of excitation in a mathematical model of ischaemic border zone. PLoS One 6:e24388 |
| Asfour, Huda; Swift, Luther M; Sarvazyan, Narine et al. (2011) Signal decomposition of transmembrane voltage-sensitive dye fluorescence using a multiresolution wavelet analysis. IEEE Trans Biomed Eng 58:2083-93 |
| House, Carrie D; Vaske, Charles J; Schwartz, Arnold M et al. (2010) Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion. Cancer Res 70:6957-67 |
| Gillum, Nikki; Karabekian, Zaruhi; Swift, Luther M et al. (2009) Clinically relevant concentrations of di (2-ethylhexyl) phthalate (DEHP) uncouple cardiac syncytium. Toxicol Appl Pharmacol 236:25-38 |
| O'Brien, Travis J; Goodsaid, Federico; Plack, Margaret et al. (2009) Development of an undergraduate pharmacogenomics curriculum. Pharmacogenomics 10:1979-86 |
| Karabekian, Zaruhi; Gillum, Nikki D; Wong, Elissa W P et al. (2009) Effects of N-cadherin overexpression on the adhesion properties of embryonic stem cells. Cell Adh Migr 3:305-10 |
| Gillum, Nikki; Sarvazyan, Narine (2008) Adhesion proteins, stem cells, and arrhythmogenesis. Cardiovasc Toxicol 8:1-13 |
| Biktashev, Vadim N; Arutunyan, Ara; Sarvazyan, Narine A (2008) Generation and escape of local waves from the boundary of uncoupled cardiac tissue. Biophys J 94:3726-38 |
Showing the most recent 10 out of 14 publications
