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

Activation of the sympathetic nervous system is ahallmark of heart failure and is positively correlated with disease progression. Catecholaminergic (C1) neurons locatedin the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload heart failure (HF). However, there is no conclusiveevidence showing acontribution of RVLM-C1 neurons to the developmentof cardiac dysfunctionin 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 arterio-venous 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 [DβH-SAP]) and measures of cardiacautonomictone,function, and arrhythmia incidence were evaluated. Cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction were present in HF rats andimproved 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 apivotal role played by RVLM-C1 neurons in cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunctionin volume overload-induced heart failure.

Source: Clinical Science - January 9, 2019 Category: Biomedical Science Authors: Andrade, D. C., Toledo, C., Diaz, H. S., Lucero, C., Arce-Alvarez, A., Oliveira, L. M., Takakura, A. C., Moreira, T. S., Schultz, H. D., Marcus, N. J., Alcayaga, J., Del Rio, R. Tags: PublishAheadOfPrint Source Type: research