Chemical Mediators of the Muscle Ergoreflex in Chronic Heart Failure

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Abstract
Background — The overactivity of ergoreceptors (intramuscular afferents sensitive to products of skeletal muscle work) may be responsible for the abnormal responses to exercise and symptoms of exercise intolerance in chronic heart failure (CHF); however, little is known of the chemical nature of the stimuli involved. We investigated biochemical factors (H + , V̇ co 2 , V̇ o 2 , H co 3 , K + , phosphate, lactate, PGE 2 , PGF 1α , and bradykinin) potentially involved in ergoreceptor activation. Methods and Results — Sixteen stable patients with CHF (64.9±2.7 years, peak V̇ o 2 15.8±0.7 mL/kg per min) and 10 age-matched controls were studied. The ergoreceptor test involved two 5-minute handgrip exercises. On one occasion, the subjects recovered normally (control recovery), whereas on the other a posthandgrip regional circulatory occlusion was induced in the exercising arm, isolating the stimulation of the ergoreceptor after exercise. The ergoreflex was quantified as the difference in ventilation between the posthandgrip regional circulatory occlusion and the control recovery periods. During the protocol, the local muscular blood effluent concentrations of metabolic mediators were assessed. Patients had an ergoreflex effect on ventilation greater than controls (4.8±1.4 versus 0.4±0.1 L/min, P 2 (3.7±0.7 versus 1.1±0.2 pg/mL), PGF 1α (16.2±2.8 versus 7.2±1.2 pg/mL), and bradykinin (2.1±0.3 versus 1.0±0.1 pg/mL), P 0.41, P Conclusions — Although multiple metabolites are concentrated in exercising muscle in CHF, only prostaglandins correlated with ergoreflex activity, suggesting these factors as potential triggers to the exaggerated ergoreflex, which is characteristic of CHF. This may have important implications for novel therapies to improve exercise tolerance.