Carotid chemoreflex and muscle metaboreflex interact to the regulation of ventilation in patients with heart failure with reduced ejection fraction

Synergism among reflexes probably contributes to exercise hyperventilation in patients with heart failure with reduced ejection fraction (HFrEF). Thus, we investigated whether the carotid chemoreflex and the muscle metaboreflex interact to the regulation of ventilation ([Formula: see text]) in HFrEF. Ten patients accomplished 4‐min cycling at 60% peak workload and then recovered for 2 min under either: (a) 21% O(2) inhalation (tonic carotid chemoreflex activity) with legs’ circulation free (inactive muscle metaboreflex); (b) 100% O(2) inhalation (suppressed carotid chemoreflex activity) with legs’ circulation occluded (muscle metaboreflex activation); (c) 21% O(2) inhalation (tonic carotid chemoreflex activity) with legs’ circulation occluded (muscle metaboreflex activation); or (d) 100% O(2) inhalation (suppressed carotid chemoreflex activity) with legs’ circulation free (inactive muscle metaboreflex) as control. [Formula: see text] , tidal volume (V(T)) and respiratory frequency (f (R)) were similar between each separated reflex (protocols a and b) and control (protocol d). Calculated sum of separated reflexes effects was similar to control. Oppositely, [Formula: see text] (mean ± SEM: Δ vs. control = 2.46 ± 1.07 L/min, p = .05) and f (R) (Δ = 2.47 ± 0.77 cycles/min, p = .02) increased versus control when both reflexes were simultaneously active (protocol c). Therefore, the carotid chemoreflex and the muscle metaboreflex interacted to [Formula: see text] regulation in a f (R)‐dependent manner in patients with HFrEF. If this interaction operates during exercise, it can have some contribution to the HFrEF exercise hyperventilation.