Chemical Mediators of the Muscle Ergoreflex in Chronic Heart Failure

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 ϩ , V CO 2 , V O 2 , HCO 3 , K ϩ , phosphate, lactate, PGE 2 , PGF 1␣ , and bradykinin) potentially involved in ergoreceptor activation. Methods and Results-Sixteen stable patients with CHF (64.9Ϯ2.7 years, peak V O 2 15.8Ϯ0.7 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 (4.8Ϯ1. Key Words: exercise Ⅲ muscles Ⅲ ventilation C hronic heart failure (CHF) is a common cardiovascular condition with both a high mortality and a high burden of morbidity. Muscle fatigue and breathlessness are major symptoms and relate to a poor prognosis; objectively, patients show reduced exercise tolerance and an increased ventilatory response to exercise, the mechanisms of which are still not completely understood. 1 An overactivation of the muscle ergoreceptor response during exercise is closely related to patient symptoms and to the ventilatory response to exercise; a putative role of this reflex in exercise intolerance in CHF has been hypothesized. 2 In particular, the muscle ergoreflexes of the forearm muscles, 2 the small muscles used in dorsiflexing the foot, 3 and the muscles of the quadriceps 4 cause an enhanced ventilatory response in this syndrome. However, the pathophysiology of such an overactivation in CHF has not yet been investigated.The ergoreflex consists of a brain-stem autonomic and ventilatory response activated by signals from the periphery, such as free nerve-ending group III and IV muscle afferents. 5 It has been hypothesized that muscle metabolic abnormalities or circulatory insufficiency of CHF might cause local overproduction and accumulation of muscle metabolic products, which activate these afferents. 6 This is in accordance with the observation of a decreased muscular metabolic capacity, attributable to structural and functional changes within the muscles, such as changes in fiber type and decreased activity of oxidative enzymes in patients with CHF. 7 The triggering factors responsible for the ergoreflex stimulation and their involvement in the abnormal exercise responses in CHF are yet to be established. We therefore set out a n...

Recommendations on the use of exercise testing in clinical practice

“…V9E at any given V9CO 2 is typically increased. Contributory factors include: premature metabolic acidaemia (reflecting reduced O 2 delivery and/or utilisation) [146,147]; increased physiological dead space [4]; increased sympathetic system activation via mechano-or pressor-receptor stimulation in the exercising muscles [148][149][150][151][152] and, possibly, contributions from cardiopulmonary vagal and sympathetic reflexes [132,153,154]. Several studies have shown that breathing pattern in CHF is more rapid and shallow than in healthy controls at any given V9E [4,155,156].…”

Skeletal Muscle Reflex in Heart Failure Patients

“…Different metabolic and humoral products have been studied in animals [7][8][9][10][11][12] and in humans, 13-15 but few investigators have investigated factors specifically involved in the ergoreflex overactivation of CHF patients. 16,17 One (or more) of these mediators may be involved as a link between alterations in muscle metabolism and/or hemodynamics present in CHF and the ventilatory response to exercise, via activation of muscle reflex.We have investigated the role of the putative triggers in muscle ergoreflex activation. The identification of the biochemical factors contributing to this effect could lead to the development of treatments aimed specifically at reducing ergoreflex overactivation, which in turn may improve symptom control in CHF patients.…”

“…Different metabolic and humoral products have been studied in animals [7][8][9][10][11][12] and in humans, [13][14][15] but few investigators have investigated factors specifically involved in the ergoreflex overactivation of CHF patients. 16,17 One (or more) of these mediators may be involved as a link between alterations in muscle metabolism and/or hemodynamics present in CHF and the ventilatory response to exercise, via activation of muscle reflex.…”

Exercício intenso e suplementação de testosterona em portadores de insuficiência cardíaca

“…No musculoesquelético há ergorreceptores que são pequenas fibras de nervos aferentes sensitivas a mudanças no metabolismo [2][3][4] . A superprodução e acúmulo de metabó-litos nos musculosesqueléticos, durante a atividade física, promovem a ativação do ergorreflexo, que leva a estímulos que aumentam de forma exagerada a ação dos sistemas ventilatório, hemodinâmico e sistema nervoso simpático 4 , colaborando para aparecimento da dispneia e intolerância aos esforços.…”

“…No musculoesquelético há ergorreceptores que são pequenas fibras de nervos aferentes sensitivas a mudanças no metabolismo [2][3][4] . A superprodução e acúmulo de metabó-litos nos musculosesqueléticos, durante a atividade física, promovem a ativação do ergorreflexo, que leva a estímulos que aumentam de forma exagerada a ação dos sistemas ventilatório, hemodinâmico e sistema nervoso simpático 4 , colaborando para aparecimento da dispneia e intolerância aos esforços. O tratamento exige otimização da terapia farmacológica e não farmacológica, o que inclui programa estruturado de exercício físico 5 que, dentre outros benefícios, proporciona melhora da hiperatividade do ergorreflexo 6 , potência funcional e qualidade de vida 7 , sendo relatado que o exercício de alta intensidade promove benefícios superiores ao exercício moderado contínuo 8,9 .…”