The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Open accessAbstract
Catecholaminergic polymorphic ventricular tachycardia (VT) is a lethal familial disease characterized by bidirectional VT, polymorphic VT, and ventricular fibrillation. Catecholaminergic polymorphic VT is caused by enhanced Ca 2+ release through defective ryanodine receptor (RyR2) channels. We used epicardial and endocardial optical mapping, chemical subendocardial ablation with Lugol’s solution, and patch clamping in a knockin (RyR2/RyR2 R4496C ) mouse model to investigate the arrhythmogenic mechanisms in catecholaminergic polymorphic VT. In isolated hearts, spontaneous ventricular arrhythmias occurred in 54% of 13 RyR2/RyR2 R4496C and in 9% of 11 wild-type ( P =0.03) littermates perfused with Ca 2+ and isoproterenol; 66% of 12 RyR2/RyR2 R4496C and 20% of 10 wild-type hearts perfused with caffeine and epinephrine showed arrhythmias ( P =0.04). Epicardial mapping showed that monomorphic VT, bidirectional VT, and polymorphic VT manifested as concentric epicardial breakthrough patterns, suggesting a focal origin in the His–Purkinje networks of either or both ventricles. Monomorphic VT was clearly unifocal, whereas bidirectional VT was bifocal. Polymorphic VT was initially multifocal but eventually became reentrant and degenerated into ventricular fibrillation. Endocardial mapping confirmed the Purkinje fiber origin of the focal arrhythmias. Chemical ablation of the right ventricular endocardial cavity with Lugol’s solution induced complete right bundle branch block and converted the bidirectional VT into monomorphic VT in 4 anesthetized RyR2/RyR2 R4496C mice. Under current clamp, single Purkinje cells from RyR2/RyR2 R4496C mouse hearts generated delayed afterdepolarization–induced triggered activity at lower frequencies and level of adrenergic stimulation than wild-type. Overall, the data demonstrate that the His–Purkinje system is an important source of focal arrhythmias in catecholaminergic polymorphic VT.
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Cites
Priori, S. G., Napolitano, C., Tiso, N., Memmi, M., Vignati, G., Bloise, R., Sorrentino, V., & Danieli, G. A. (2001) · Circulation · doi:10.1161/01.cir.103.2.196 · Cited by 1,378 · cited 4×
“The hypotheses investigated were (1) 2 alternating sources of epicardial ventricular activity located, respectively, 1 in the RV and 1 in the LV; (2) alternating epicardial and endocardial discharges, as previously proposed25; (3) a single Purkinje focus with alternating bundle branch block.”
BackgroundMethodInfluentialSelf-citation
Cited by
Role of the Autonomic Nervous System in Modulating Cardiac Arrhythmias
Shen, M. J., & Zipes, D. P. (2014) · Circulation Research · doi:10.1161/circresaha.113.302549 · Cited by 867
Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans
Watanabe, H., Chopra, N., Laver, D., Hwang, H. S., Davies, S. S., Roach, D. E., Duff, H. J., Roden, D. M., Wilde, A. A. M., & Knollmann, B. C. (2009) · Nature Medicine · doi:10.1038/nm.1942 · Cited by 608
Cardiac electrophysiology in mice: a matter of size
Kaese, S., & Verheule, S. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00345 · Cited by 196
Park, S.-J., Zhang, D., Qi, Y., Li, Y., Lee, K. Y., Bezzerides, V. J., Yang, P., Xia, S., Kim, S. L., Liu, X., et al. (2019) · Circulation · doi:10.1161/circulationaha.119.039711 · Cited by 140
Metadata
- Authors
- Cerrone, M., Noujaim, S. F., Tolkacheva, E. G., Talkachou, A., O’Connell, R., Berenfeld, O., Anumonwo, J., Pandit, S. V., Vikstrom, K., Napolitano, C., Priori, S. G., & Jalife, J.
- Venue
- Circulation Research
- Published
- 2007-11-09
- Volume
- 101
- Issue
- 10
- Pages
- 1039-1048
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2146053159
- Cited by
- 285
- References
- 1
- FWCI
- 11.88
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Cerrone, M., Noujaim, S. F., Tolkacheva, E. G., Talkachou, A., O’Connell, R., Berenfeld, O., Anumonwo, J., Pandit, S. V., Vikstrom, K., Napolitano, C., Priori, S. G., & Jalife, J. (2007). Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia. Circulation Research. https://doi.org/10.1161/circresaha.107.148064
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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