The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Bidirectional Ventricular Tachycardia and Fibrillation Elicited in a Knock-In Mouse Model Carrier of a Mutation in the Cardiac Ryanodine Receptor
Abstract
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death. The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor. In vitro functional characterization of mutant RyR2 channels showed altered behavior on adrenergic stimulation and caffeine administration with enhanced calcium release from the sarcoplasmic reticulum. As of today no experimental evidence is available to demonstrate that RyR2 mutations can reproduce the arrhythmias observed in CPVT patients. We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias. Twenty-six mice (12 wild-type (WT) and 14RyR R4496C ) underwent exercise stress testing followed by epinephrine administration: none of the WT developed ventricular tachycardia (VT) versus 5/14 RyR R4496C mice ( P =0.02). Twenty-one mice (8 WT, 8 RyR R4496C , and 5 RyR R4496C pretreated with beta-blockers) received epinephrine and caffeine: 4/8 (50%) RyR R4496C mice but none of the WT developed VT ( P =0.02); 4/5 RyR R4496C mice pretreated with propranolol developed VT ( P =0.56 nonsignificant versus RyR R4496C mice). These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation. Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias.
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Self-citationPriori, S. G., Napolitano, C., Memmi, M., Colombi, B., Drago, F., Gasparini, M., DeSimone, L., Coltorti, F., Bloise, R., Keegan, R., et al. (2002) · Circulation · doi:10.1161/01.cir.0000020013.73106.d8 · Cited by 1,173
Self-citationCatecholaminergic Polymorphic Ventricular Tachycardia in Children: A 7-Year Follow-up of 21 Patients
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Self-citationLaitinen, P. J., Brown, K. M., Piippo, K., Swan, H., Devaney, J. M., Brahmbhatt, B., Donarum, E. A., Marino, M., Tiso, N., Viitasalo, M., et al. (2001) · Circulation · doi:10.1161/01.cir.103.4.485 · Cited by 726
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Inherited Arrhythmogenic Diseases: The Complexity Beyond Monogenic Disorders
Priori, S. (2004) · Circulation Research · doi:10.1161/01.res.0000115750.12807.7e · Cited by 97
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Garcia-Gras, E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27751 · Cited by 623
Knollmann, B. C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29128 · Cited by 444
ter Keurs, H. E. D. J., & Boyden, P. A. (2007) · Physiological Reviews · doi:10.1152/physrev.00011.2006 · Cited by 356
van Oort, R. J., McCauley, M. D., Dixit, S. S., Pereira, L., Yang, Y., Respress, J. L., Wang, Q., De Almeida, A. C., Skapura, D. G., Anderson, M. E., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.982298 · Cited by 310
Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Cerrone, M., Noujaim, S. F., Tolkacheva, E. G., Talkachou, A., O’Connell, R., Berenfeld, O., Anumonwo, J., Pandit, S. V., Vikstrom, K., Napolitano, C., et al. (2007) · Circulation Research · doi:10.1161/circresaha.107.148064 · Cited by 285
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Metadata
- Authors
- Cerrone, M., Colombi, B., Santoro, M., di Barletta, M. R., Scelsi, M., Villani, L., Napolitano, C., & Priori, S. G.
- Venue
- Circulation Research
- Published
- 2005-05-27
- Volume
- 96
- Issue
- 10
- Pages
- e77-82
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W1996439106
- Cited by
- 283
- References
- 12
- FWCI
- 15.49
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Bidirectional Ventricular Tachycardia and Fibrillation Elicited in a Knock-In Mouse Model Carrier of a Mutation in the Cardiac Ryanodine Receptor. https://app.cochat.ai/papers/10.1161/01.res.0000169067.51055.72
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- Cerrone, M., Colombi, B., Santoro, M., di Barletta, M. R., Scelsi, M., Villani, L., Napolitano, C., & Priori, S. G. (2005). Bidirectional Ventricular Tachycardia and Fibrillation Elicited in a Knock-In Mouse Model Carrier of a Mutation in the Cardiac Ryanodine Receptor. Circulation Research. https://doi.org/10.1161/01.res.0000169067.51055.72
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