Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure
Andrade, David C.
Pontificia Universidad Catolica de Chile
Toledo, Camilo
Pontificia Universidad Catolica de Chile
Diaz, Hugo S.
Pontificia Universidad Catolica de Chile
Lucero, Claudia
Pontificia Universidad Catolica de Chile
Arce-Alvarez, Alexis
Pontificia Universidad Catolica de Chile
Oliveira, Luiz M.
Universidade de Sao Paulo
Takakura, Ana C.
Universidade de Sao Paulo
Moreira, Thiago S.
Universidade de Sao Paulo
Schultz, Harold D.
University of Nebraska System
Marcus, Noah J.
Des Moines University
Alcayaga, Julio
Universidad de Chile
Del Rio, Rodrigo
Journal
Clinical Science
ISSN
0143-5221
1470-8736
Open Access
closed
Volume
133
Start page
393
End page
405
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-beta hydroxylase saporin [D beta H-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 D beta H-SAP toxin treatment. Most importantly, the progressive decline in fractional shortening observed in HF rats was reduced by D beta H-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.