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

Author(s):Show less -

Andrade, David C. ^{[1, 2]} ; Toledo, Camilo ^{[1, 3]} ; Diaz, Hugo S. ^[1] ; Lucero, Claudia ^[1] ; Arce-Alvarez, Alexis ^{[1, 4]} ; Oliveira, Luiz M. ^[5] ; Takakura, Ana C. ^[5] ; Moreira, Thiago S. ^[6] ; Schultz, Harold D. ^[7] ; Marcus, Noah J. ^[8] ; Alcayaga, Julio ^[9] ; Del Rio, Rodrigo ^{[1, 3, 10]}

Affiliation

^[1] Pontificia Univ Catolica Chile, Dept Physiol, Lab Cardioresp Control, Santiago - Chile

^[2] Univ Mayor, Ctr Invest Fisiol Ejercicio, Santiago - Chile

^[3] Pontificia Univ Catolica Chile, Ctr Envejecimiento & Regenerac CARE UC, Santiago - Chile

^[4] Univ Catolica Silva Henriquez, Fac Salud, Escuela Kinesiol, Santiago - Chile

^[5] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil

^[7] Univ Nebraska Med Ctr, Dept Cellular & Integrat Physiol, Omaha, NE - USA

^[8] Des Moines Univ, Dept Physiol & Pharmacol, Des Moines, IA - USA

^[9] Univ Chile, Fac Ciencias, Lab Fisiol Celular, Santiago - Chile

^[10] Univ Magallanes, Ctr Excelencia Biomed Magallanes CEBIMA, Punta Arenas - Chile

• Document type: Journal article
• Source: Clinical Science; v. 133, n. 3, p. 393-405, FEB 14 2019.
• Web of Science Citations: 4

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-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. (AU)

• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants