Exercise intolerance and fatigue in chronic heart failure: is there a role for group III/IV afferent feedback?

Abstract

Exercise intolerance and early fatiguability are hallmark symptoms of chronic heart failure. While the malfunction of the heart is certainly the leading cause of chronic heart failure, the patho-physiological mechanisms of exercise intolerance in these patients are more complex, multifactorial and only partially understood. Some evidence points towards a potential role of an exaggerated afferent feedback from group III/IV muscle afferents in the genesis of these symptoms. Overactivity of feedback from these muscle afferents may cause exercise intolerance with a double action: by inducing cardiovascular dysregulation, by reducing motor output and by facilitating the development of central and peripheral fatigue during exercise. Importantly, physical inactivity appears to affect the progression of the syndrome negatively, while physical training can partially counteract this condition. In the present review, the role played by group III/IV afferent feedback in cardiovascular regulation during exercise and exercise-induced muscle fatigue of healthy people and their potential role in inducing exercise intolerance in chronic heart failure patients will be summarised.

Exercise intolerance and skeletal muscle metaboreflex activity in chronic heart failure: Do we need to recruit more muscle in exercise training?

“…Angius and Crisafuli 1 correctly include recent studies reporting increased activation of the metaboreflex in patients using beta blockers 11,12 compared with previous studies (beta blockers in ≤30% of patients). 3,4,6 Based on the consideration that the metaboreflex is mediated by the sympathetic nervous system and that beta blockers are adrenergic blockers, they could affect their hyperactivation by decreasing the sympathetic tonus, potentially influencing the metaboreflex activation.…”

“…In the current issue of this journal, Angius and Crisafuli 1 review the literature for the role of an exaggerated feedback from group III/IV muscle afferents in the genesis of fatigue by bringing forward the muscle hypothesis. The muscle hypothesis describes changes in skeletal muscle metabolism, structure and function where an increased activation of metaboreceptors (and chemoreceptors responding to changes in blood gas concentrations) sensitive to the metabolic changes occurring during exercise produces an exaggerated feedback from group III/IV muscle afferents (termed the metaboreflex).…”

“…Although Angius and Crisafuli 1 focus on muscle fatigue, another aspect that needs to be reported is the role of the metaboreflex in the genesis of dyspnoea, which appears to be at least partially responsible for exercise intolerance in patients with CHF. The reflex network arising from the exercising muscle not only activates autonomic circuits, but also medullary ventilatory centres resulting in an excessive ventilatory response to exercise that presents as exertional dyspnoea.…”

“…Based on these observations, the recruitment of more muscle in exercise training appears to be associated with enhanced benefits in patients with CHF, with the attenuation of metaboreflex hyperactivity arising as an attractive mechanism for improvement. However, Angius and Crisafuli 1 rightfully suggest that further studies are needed to evaluate the effect of metaboreflex activity in producing exaggerated ventilatory responses, central and peripheral fatigue in patients with CHF, and also its potential attenuation in response to different and combined exercise training modalities.…”

Editors’ presentation: Focus on cardiomyopathy and heart failure

“…16 In the current issue of this Journal, Angius and Crisafuli review the literature for the role of an exaggerated feedback from group III/IV muscle afferents in the genesis of fatigue by bringing forward the muscle hypothesis. 17 The muscle hypothesis suggests that changes in skeletal muscle metabolism, structure and function in HF produce exaggerated feedback from group III/IV muscle afferents (termed the metaboreflex) sensitive to the metabolic changes occurring during exercise. This exaggerated afferent feedback coming from these fibres potentially causes haemodynamic and ventilatory dysregulation, with excessive sympathoexcitation arteriolar constriction and ventilatory response slope for CO 2 during exercise.…”