Ryanodine receptor stabilization therapy suppresses Ca2+- based arrhythmias in a novel model of metabolic HFpEF.
J Mol Cell Cardiol
; 195: 68-72, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-39053573
ABSTRACT
Heart Failure with preserved ejection fraction (HFpEF) has a high rate of sudden cardiac death (SCD) and empirical treatment is ineffective. We developed a novel preclinical model of metabolic HFpEF that presents with stress-induced ventricular tachycardia (VT). Mechanistically, we discovered arrhythmogenic changes in intracellular Ca2+ handling distinct from the changes pathognomonic for heart failure with reduced ejection fraction. We further show that dantrolene, a stabilizer of the ryanodine receptor Ca2+ channel, attenuates HFpEF-associated arrhythmogenic Ca2+ handling in vitro and suppresses stress-induced VT in vivo. We propose ryanodine receptor stabilization as a mechanistic approach to mitigation of malignant VT in metabolic HFpEF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Arritmias Cardíacas
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Calcio
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Canal Liberador de Calcio Receptor de Rianodina
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Dantroleno
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Modelos Animales de Enfermedad
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Insuficiencia Cardíaca
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Mol Cell Cardiol
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos