Brainstem C1 neurons mediate heart failure decompensation and mortality during acute salt loading

Area of Science:

• Cardiovascular Science
• Neuroscience
• Physiology

Background:

• Heart failure (HF) is a global epidemic with high mortality despite treatment advances.
• Kidney dysfunction in HF leads to sodium retention and fluid overload, worsening outcomes.
• Brainstem pre-sympathetic neurons (C1) in the RVLM are implicated in HF sympathetic regulation.

Purpose of the Study:

• To investigate the role of RVLM C1 neurons in driving cardiorespiratory decompensation and sudden death during salt loading in HF rats.
• To determine if RVLM C1 neurons mediate sympathetic overactivity and breathing disorders in HF with preserved ejection fraction (HFpEF) under salt-loaded conditions.

Main Methods:

• Induction of HFpEF in rats via arteriovenous shunt.
• Selective bilateral ablation of RVLM C1 neurons using a targeted toxin.
• High sodium diet and water administration to induce HF decompensation.
• Assessment of cardiac function, autonomic function, breathing patterns, and survival rates.

Main Results:

• Salt loading significantly decreased survival rates in HFpEF rats (10% survival).
• HFpEF rats on high salt exhibited increased cardiac sympathetic drive and severe disordered breathing with more hypoxia.
• Ablation of RVLM C1 neurons partially reduced sympathoexcitation, improved breathing, and decreased mortality in salt-loaded HFpEF rats.
• Hypoxia, not high sodium, was identified as the primary cause of impaired cardiomyocyte calcium handling.

Conclusions:

• RVLM C1 neurons significantly contribute to acute HF decompensation during salt loading.
• This contribution involves increased sympathetic outflow and hypoxia-related breathing disorders.
• These mechanisms may impair cardiac contractility via cardiomyocyte calcium mishandling, increasing HF morbidity and mortality.