Group III/IV muscle afferents impair limb blood flow during exercise in patients with heart failure

Abstract

Patients with heart failure (HF) are characterized by altered muscle afferent feedback which might account for their hemodynamic and autonomic reflex abnormalities. We investigated the influence of group III/IV muscle afferents on the circulatory response to rhythmic exercise in HF. Nine patients (NYHA class II) performed single leg knee extensor exercise (25/50/80% peak workload) under both control conditions (Ctrl) and with lumbar intrathecal fentanyl impairing μ‐opioid receptor‐sensitive muscle afferents. Cardiac output (Q) and femoral blood flow (QL) were determined, and arterial/venous blood samples were collected at each workload. Fentanyl had no effect at rest. During exercise, Q was 8–13% lower with Fentanyl, secondary to a 13% reduction in stroke volume and a 2–5% reduction in heart rate. Lower norepinephrine spillover during Fentanyl exercise implicated a reduced sympathetic outflow and likely accounted for the 25% increase in leg vascular conductance. As a result of this attenuated sympathoexcitation, QL was, despite a 4% lower blood pressure, 10–14% higher during exercise with Fentanyl. Although leg O2 delivery was higher during exercise with Fentanyl, arteriovenous O2 difference remained unchanged resulting in 10–17% increase in leg O2 consumption (p<0.05). Thus, although group III/IV muscle afferents represent a key determinant of the central hemodynamic response in HF, our findings also reveal that these sensory neurons cause a sympathetically‐mediated impairment of QL during rhythmic exercise in this population.