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(Circulation. 2003;107:300.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Skeletal Muscle Reflex in Heart Failure Patients

Role of Hydrogen

Adam C. Scott, BSc; Roland Wensel, MD; Constantinos H. Davos, MD, PhD; Panagiota Georgiadou, MD; Michael Kemp, MSc, MRCPath; James Hooper, MD, FRCPath; Andrew J.S. Coats, DM, FRCP, FESC; Massimo F. Piepoli, MD, PhD, FESC

From the National Heart and Lung Institute, and Royal Brompton Hospital, Imperial College School of Science, Technology and Medicine, London, United Kingdom.

Correspondence to Massimo Piepoli, MD, Heart Failure Unit, Royal Brompton Hospital, Sydney St, London, SW3 6NP, United Kingdom. E-mail m.piepoli{at}ic.ac.uk

Background— An important role of the increased stimulation of skeletal muscle ergoreceptors (intramuscular afferents sensitive to products of muscle work) in the genesis of symptoms of exertion intolerance in chronic heart failure (CHF) has been proposed. With the use of selective infusions and dietary manipulation methods, we sought to identify the role of H⁺, K⁺, lactate, and peripheral hemodynamics on ergoreflex overactivation.

Methods and Results— Ten stable CHF patients (aged 67.9±2.5 years, peak oxygen uptake 16.3±1.2 mL · kg^-1 · min^-1) and 10 age-matched and sex-matched healthy subjects were studied. The ergoreflex contribution to ventilation was assessed by post-handgrip regional circulatory occlusion (PH-RCO) and computed as the difference in ventilation between PH-RCO and a control run without PH-RCO. This test was performed on 6 separate occasions. On each occasion a different chemical was infused (insulin, sodium nitroprusside, sodium bicarbonate, dopamine, or saline) or a 36-hour glucose-free diet was undertaken before the test. During all stages of the protocol, the local muscular blood effluent concentrations of H⁺, K⁺, glucose, and lactate were assessed. An ergoreflex effect on the ventilatory response was seen in patients (versus control subjects) during the saline infusions (6.7±2.3 L/min versus -0.1±0.5 L/min, P<0.01). The only intervention to significantly lower the ergoreflex was sodium bicarbonate (0.4±0.3 L/min versus -0.2±0.4 L/min in control subjects, P=NS; versus saline P<0.05), which also reduced H⁺ concentration during exercise (47.4±1.3 versus 50.0±1.4 nmol/L on saline, P<0.05).

Conclusion— A reduction of the H⁺ concentration by infusion of sodium bicarbonate abolishes the increased ergoreceptor activity in CHF, suggesting a role of H⁺ in ergoreflex activation, either directly or indirectly.

Key Words: heart failure • muscles • nervous system, autonomic • reflex • ventilation

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