Group III/IV muscle afferents impair limb blood in patients with chronic heart failure

Marcus Amann
Massimo Venturelli
Stephen J. Ives, Skidmore College
David E. Morgan
Benjamin S. Gmelch
Melissa A.H. Witman
H. Jonathan Groot
D. Walter Wray
Josef Stehlik
Russell S. Richardson



To better understand the hemodynamic and autonomic reflex abnormalities in heart-failure patients (HF), we investigated the influence of group III/IV muscle afferents on their cardiovascular response to rhythmic exercise.


Nine HF-patients (NYHA class-II, mean left ventricular ejection-fraction: 27 ± 3%) performed single leg knee-extensor exercise (25/50/80% peak-workload) under control conditions 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 collected at each workload. Exercise-induced fatigue was estimated via pre/post-exercise changes in quadriceps strength. There were no hemodynamic differences between conditions at rest. During exercise, Q was 8–13% lower with Fentanyl-blockade, secondary to significant reductions in stroke volume and heart rate. Lower norepinephrine spillover during exercise with Fentanyl revealed an attenuated sympathetic outflow that likely contributed to the 25% increase in leg vascular conductance (p < 0.05). Despite a concomitant 4% reduction in blood pressure, QL was 10–14% higher and end-exercise fatigue attenuated by 30% with Fentanyl-blockade (p < 0.05).


Although group III/IV muscle afferents play a critical role for central hemodynamics in HF-patients, it also appears that these sensory neurons cause excessive sympatho-excitation impairing QL which likely contributes to the exercise intolerance in this population.