Published Online
on December 23, 2002

A more recent version of this article appeared on January 21, 2003

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Submitted on June 20, 2002
Revised on September 26, 2002
Accepted on September 26, 2002

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, and 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.

^* To whom correspondence should be addressed. 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, automatic • reflex • ventilation

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