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Ivabradine prevents deleterious effects of dopamine therapy in heart failure: No role for HCN4 overexpression.
Paterek, Aleksandra; Sochanowicz, Barbara; Okninska, Marta; Smigielski, Witold; Kruszewski, Marcin; Mackiewicz, Urszula; Maczewski, Michal; Leszek, Przemyslaw.
Afiliação
  • Paterek A; Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland.
  • Sochanowicz B; Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warsaw, Poland.
  • Okninska M; Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland.
  • Smigielski W; Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, The Cardinal Stefan Wyszynski National Institute of Cardiology, Warsaw, Poland.
  • Kruszewski M; Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warsaw, Poland; Department of Molecular Biology and Translational Research, Institute of Rural Health, Lublin, Poland; Department of Medical Biology and Translational Research, Faculty of Medicine, Unive
  • Mackiewicz U; Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland.
  • Maczewski M; Department of Clinical Physiology, Centre of Postgraduate Medical Education, Warsaw, Poland. Electronic address: michal.maczewski@cmkp.edu.pl.
  • Leszek P; Department of Heart Failure and Transplantology, The Cardinal Stefan Wyszynski National Institute of Cardiology, Warsaw, Poland.
Biomed Pharmacother ; 136: 111250, 2021 Apr.
Article em En | MEDLINE | ID: mdl-33450487
ABSTRACT

BACKGROUND:

Exacerbations of chronic heart failure (CHF) are often treated with catecholamines to provide short term inotropic support, but this strategy is associated with long-term detrimental hemodynamic effects and increased ventricular arrhythmias (VA), possibly related to increased heart rate (HR). We hypothesized that ivabradine may prevent adverse effects of short-term dopamine treatment in CHF.

METHODS:

Rats with post-myocardial infarction CHF received 2-week infusion of saline, dopamine(D), ivabradine(I) or D&I; cardiac function was assessed using echocardiography and pressure-volume loops while VA were assessed using telemetric ECG recording. Expression of HCN4, a potentially proarrhythmic channel blocked by ivabradine, was assessed in left ventricular (LV) myocardium. HCN4 expression was also assessed in human explanted normal and failing hearts and correlated with VA.

FINDINGS:

Dopamine infusion had detrimental effects on hemodynamic parameters and LV remodeling and induced VA in CHF rats, while ivabradine completely prevented these effects. CHF rats demonstrated HCN4 overexpression in LV myocardium, and ivabradine and, unexpectedly, dopamine prevented this. Failing human hearts also exhibited HCN4 overexpression in LV myocardium that was unrelated to patient's sex, CHF etiology, VA severity or plasma NT-proBNP.

INTERPRETATION:

HR reduction offered by ivabradine may be a feasible strategy to extract benefits of inotropic support in CHF exacerbations, avoiding detrimental effects on CHF biology or VA. Ivabradine may offer additional beneficial effects in this setting, going beyond pure HR reduction, however prevention of ventricular HCN4 overexpression is unlikely to play a major role.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Canais de Potássio / Dopamina / Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização / Ivabradina / Insuficiência Cardíaca / Frequência Cardíaca / Antiarrítmicos / Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Polônia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Canais de Potássio / Dopamina / Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização / Ivabradina / Insuficiência Cardíaca / Frequência Cardíaca / Antiarrítmicos / Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Polônia