Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure

David C. Andrade, Camilo Toledo, Hugo S. Díaz, Claudia Lucero, Alexis Arce-Álvarez, Luiz M. Oliveira, Ana C. Takakura, Thiago S. Moreira, Harold D. Schultz, Noah J. Marcus, Julio Alcayaga, Rodrigo Del Rio

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Activation of the sympathetic nervous system is a hallmark of heart failure (HF) and is positively correlated with disease progression. Catecholaminergic (C1) neurons located in the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload HF. However, there is no conclusive evidence showing a contribution of RVLM-C1 neurons to the development of cardiac dysfunction in the setting of HF. Therefore, the aim of this study was to determine the role of RVLM-C1 neurons in cardiac autonomic control and deterioration of cardiac function in HF rats. A surgical arteriovenous shunt was created in adult male Sprague-Dawley rats to induce HF. RVLM-C1 neurons were selectively ablated using cell-specific immunotoxin (dopamine-β hydroxylase saporin [DβH-SAP]) and measures of cardiac autonomic tone, function, and arrhythmia incidence were evaluated. Cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction were present in HF rats and improved after DβH-SAP toxin treatment. Most importantly, the progressive decline in fractional shortening observed in HF rats was reduced by DβH-SAP toxin. Our results unveil a pivotal role played by RVLM-C1 neurons in cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction in volume overload-induced HF.

Original languageEnglish (US)
Pages (from-to)393-405
Number of pages13
JournalClinical Science
Volume133
Issue number3
DOIs
StatePublished - Feb 14 2019

ASJC Scopus subject areas

  • Medicine(all)

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