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Prolonged Ca2+ release refractoriness and T-tubule disruption as determinants of increased propensity to cardiac alternans in the hypertensive heart disease.
Mariángelo, Juan Ignacio Elio; Di Marzio, Gabriel Darío; Gonano, Luis Alberto; Said, Matilde; Mundiña-Weilenmann, Cecilia.
Afiliação
  • Mariángelo JIE; Centro de Investigaciones Cardiovasculares, CCT-CONICET La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
  • Di Marzio GD; Centro de Investigaciones Cardiovasculares, CCT-CONICET La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
  • Gonano LA; Centro de Investigaciones Cardiovasculares, CCT-CONICET La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
  • Said M; Centro de Investigaciones Cardiovasculares, CCT-CONICET La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
  • Mundiña-Weilenmann C; Centro de Investigaciones Cardiovasculares, CCT-CONICET La Plata, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
Acta Physiol (Oxf) ; 238(2): e13969, 2023 06.
Article em En | MEDLINE | ID: mdl-36971744
AIM: Cardiac alternans is a dynamical phenomenon linked to the genesis of severe arrhythmias and sudden cardiac death. It has been proposed that alternans is caused by alterations in Ca2+ handling by the sarcoplasmic reticulum (SR), in both the SR Ca2+ uptake and release processes. The hypertrophic myocardium is particularly prone to alternans, but the precise mechanisms underlying its increased vulnerability are not known. METHODS: Mechanical alternans (intact hearts) and Ca2+ alternans (cardiac myocytes) were studied in spontaneously hypertensive rats (SHR) during the first year of age after the onset of hypertension and compared with age-matched normotensive rats. Subcellular Ca2+ alternans, T-tubule organization, SR Ca2+ uptake, and Ca2+ release refractoriness were measured. RESULTS: The increased susceptibility of SHR to high-frequency-induced mechanical and Ca2+ alternans appeared when the hypertrophy developed, associated with an adverse remodeling of the T-tubule network (6 mo). At the subcellular level, Ca2+ discordant alternans was also observed. From 6 mo of age, SHR myocytes showed a prolongation of Ca2+ release refractoriness without alterations in the capacity of SR Ca2+ removal, measured by the frequency-dependent acceleration of relaxation. Sensitizing SR Ca2+ release channels (RyR2) by a low dose of caffeine or by an increase in extracellular Ca2+ concentration, shortened refractoriness of SR Ca2+ release, and reduced alternans in SHR hearts. CONCLUSIONS: The tuning of SR Ca2+ release refractoriness is a crucial target to prevent cardiac alternans in a hypertrophic myocardium with an adverse T-tubule remodeling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Hipertensão Limite: Animals Idioma: En Revista: Acta Physiol (Oxf) Assunto da revista: FISIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Hipertensão Limite: Animals Idioma: En Revista: Acta Physiol (Oxf) Assunto da revista: FISIOLOGIA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina País de publicação: Reino Unido