Carotid body ablation improves survival, breathing disorders and autonomic control in heart failure rats

Abstract

Sympathetic hyperactivity and breathing instability contribute to decompensation during chronic heart failure (CHF). Enhanced carotid body (CB) chemoreflex drive has been related to increased sympathetic outflow and breathing disorders in CHF. We hypothesized that ablation of CB afferents (CBA) improves cardiorespiratory function and survival in CHF. Selective CBA was performed on male Sprague‐Dawley rats after 16 weeks (wk) of coronary artery ligation (EF < 45%). Resting breathing and ventilatory responses to acute hypoxia (FiO2‐10%) were measured by plethysmography prior to and one wk after CBA/sham surgery. Heart rate (HRV) and systolic blood pressure variability (BPV) and spontaneous baroreflex gain (BG) were similarly determined at rest. Neuronal activation was assessed in the rostral ventrolateral medulla (RVLM) at the end of the study using Fra‐1 expression. CHF rats compared to sham exhibited elevated apnea incidence, hypoxic ventilatory responses, LF/HF HRV, LF‐BPV, and RVLM Fra‐1 expression and decreased BG. CBA in CHF rats decreased (pre‐ vs. post‐CBA, P < .05), LF/HF HRV (2.1±0.3 vs. 0.9±0.2), LF‐BPV (18.4±4.5 vs. 7.2±2.0 mmHg2), apnea frequency (16.8±1.8 vs. 10.6±0.6 events/h), RVLM Fra‐1 expression (1.5±0.1 vs. 0.9±0.1 a.u.), and increased BG (1.0±0.1 vs. 1.9±0.3 ms/mmHg) to levels comparable to sham rats. Mortality rate at 16 wk post infarct was elevated in CHF compared to sham (33% vs. 7%). CBA at 2 wk post infarct reduced the mortality rate in CHF rats at 16 wk to 15%. Our results show that CBA reduces hyperactivation of the RVLM and improves cardiorespiratory control and survival in CHF rats. Supported by NIH PO1‐HL62222.