ReviewCardiovascular and ventilatory control during exercise in chronic heart failure: Role of muscle reflexes
Introduction
Patients with chronic heart failure (CHF) are severely limited in their daily activities, with early occurrence of dyspnea or fatigue. Until recently, the derangement of central haemodynamics was considered the leading cause and treatment aimed at relieving pressure and volume overload. Nevertheless, this approach has not led to any improvement in prognosis and quality of life [1]. Although abnormal central haemodynamics is the cause of symptoms in acute heart failure, this is not the case in CHF. In fact, little or no correlation was found between indices of central circulation or pulmonary function and exercise tolerance expressed as peak oxygen consumption [2].
It has been suggested that changes in the periphery rather than left ventricular performance itself may limit exercise capacity in these patients. A great bulk of evidence has pointed towards the existence of a reflex network that becomes hyperactive secondary to skeletal muscle alterations and may contribute to exercise intolerance [3]. The over-activation of signals originating from skeletal muscle receptors (mechano-metaboreceptors) is an intriguing hypothesis recently proposed to explain the origin of symptoms and the beneficial effect of exercise training in the CHF syndrome.
The purpose of this review is to present the latest data on the genesis of exercise intolerance in CHF patients. In the first part, general concepts about the physiology of cardiovascular regulation during exercise and the role of reflexes of muscular origin are discussed. The second part mainly focuses on the potential role played by such a muscular reflex de-arrangement in inducing exercise intolerance in CHF.
Section snippets
Cardiovascular and ventilatory control during exercise: general concepts
During exercise the haemodynamic and ventilatory responses are under the control of the autonomic nervous system, which depends on inputs from the cerebral motor cortex and the peripheral afferents (baroreceptors and mechano-metaboreceptors) [4], [5]. This system regulates cardiac output, vascular conductance and ventilation in an attempt to provide sufficient oxygenated blood flow and to wash out metabolic end-products of exercising muscle.
At the onset of exercise, the motor cortex (“central
Cardiovascular and ventilatory reflexes arising from mechanical and chemical receptors within muscle
A circulatory and respiratory controlling neural mechanism linked to metabolic and mechanical events occurring within active muscle is termed “the exercise pressor reflex” [8]. During exercise, metabolites such as lactic acid, adenosine, phosphate, kinins, and cations are produced in skeletal muscle. These substances accumulate with increasing stress and, when O2 delivery cannot match the metabolic needs of the contracting muscle, trigger the muscle metaboreceptors. This in turn leads to a
Consequences of metaboreflex and mechanoreflex activation
The typical haemodynamic consequence of metaboreflex activation is a rise in arterial blood pressure. This response is achieved primarily by an increase in systemic vascular resistance due to peripheral sympathetic vasoconstriction, while the effect on heart rate is variable [7]. Two approaches can be used to study metaboreflex: during effort by reducing muscle blood flow or at the cessation of effort by reducing blood flow and causing post-exercise ischemia which traps metabolites produced
Chronic heart failure: a complex and multifactorial syndrome
CHF is a multi-faceted syndrome which may be defined as the inability of the heart to meet the demands of the tissues during exercise and sometimes even at rest. Secondary compensatory mechanisms develop, including activation of the sympathetic, renin–angiotensin–aldosterone, vasopressin and atrial natriuretic peptide systems. These systems are thought to be initially beneficial in supporting the poorly functioning heart but, with prolonged activation, they lead to increased peripheral vascular
The muscle hypothesis and the metaboreflex
The “muscle hypothesis” speculates that one possible explanation for sympathetic overdrive is an exaggerated metaboreflex activity that takes place in response to chronic under-perfusion and metabolic changes occurring in the contracting muscle. This reflex overactivity leads to enhanced vasoconstriction and blood pressure increments in response to exercise, responsible, at least in part, for the exercise intolerance observed in CHF patients. The “hypothesis” proposes that CHF is a vicious
Future directions
As stated above, some studies indicate that the mechanoreflex mediates the haemodynamic dys-regulation observed in CHF. Thus, the problem of whether both muscle receptors (i.e. mechano- and metaboreceptors) are involved in the genesis of the exaggerated exercise pressor reflex activity observed in CHF still remains to be solved.
From a clinical perspective it would be useful to verify whether the chemical blockage of receptors mediating the metaboreflex may limit the excessive sympathetic
Conclusions and perspectives
According to the “muscle hypothesis” it would be more appropriate and effective to treat the cause, namely skeletal muscle abnormalities, rather than treating the consequences of ergoreflex activation such as peripheral vasoconstriction and sympathetic activation. Thus, the practical consequence would be the prescription of physical activity and the adoption of an active lifestyle in these subjects as an effective means to treat peripheral abnormalities. Randomised controlled trials have shown
References (63)
- et al.
Impaired skeletal muscle nutritive flow during exercise in patients with congestive heart failure: role of cardiac pump dysfunction as determined by the effect of dobutamine
Am J Cardiol
(1984) - et al.
Lack of correlation between exercise capacity and indexes of resting left ventricular performance in heart failure
Am J Cardiol
(1981) - et al.
Abnormalities of skeletal muscle in patients with chronic heart failure
Int J Cardiol
(1988) - et al.
Physical training improves skeletal muscle metabolism in patients with chronic heart failure
J Am Coll Cardiol
(1993) - et al.
The ergoreflex in patients with chronic stable heart failure
Int J Cardiol
(1999) - et al.
Effects of endurance training on mitochondrial ultrastructure and fiber type distribution in skeletal muscle of patients with stable chronic heart failure
J Am Coll Cardiol
(1997) - et al.
Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity
Int J Cardiol
(2002) - et al.
Contribution of muscle afferents to hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure
Circulation
(1996) - et al.
Hemodynamics during active and passive recovery from a single bout of supramaximal exercise
Eur J Appl Physiol
(2003) - et al.
Neural control of cardiovascular responses and of ventilation during dynamic exercise in man
J Physiol (Lond)
(1993)
Muscle metaboreceptors in hemodynamic, autonomic and ventilatory response to exercise in man
Am J Physiol
Muscle metaboreflex-induced increases in stroke volume
Med Sci Sports Exerc
The exercise pressor reflex: its cardiovascular effects, afferent mechanisms, and central pathways
Ann Rev Physiol
Effect of static muscular contraction on impulse activity of group III and IV afferents in cats
J Appl Physiol
Responses of group III and IV afferents to dynamic exercise
J Appl Physiol
Muscle afferent contributions to the cardiovascular response to isometric exercise
Exp Physiol
A perspective on the muscle reflex: implications for congestive heart failure
J Appl Physiol
The exercise pressor reflex in health and disease
Exp Physiol
Muscle metaboreflex contribution to sinus node regulation during static exercise
Circulation
Enhancement of parasympathetic cardiac activity during activation of muscle metaboreflex in humans
J Appl Physiol
Sympathetic-parasympathetic interaction and accentuated antagonism in conscious dogs
Am J Physiol (Heart Circ Physiol)
Muscle metaboreflex increases ventricular performance in conscious dogs
Am J Physiol (Heart Circ Physiol)
Muscle metaboreflex control of ventricular contractility during dynamic exercise
Am J Physiol (Heart Circ Physiol)
Modulation of cardiac contractility by muscle metaboreflex following efforts of different intensities in humans
Am J Physiol (Heart Circ Physiol)
WISE 2005: Stroke volume changes contribute to the pressor response during ischemic handgrip exercise in females
J Appl Physiol
Muscle chemoreflex-induced increases in right atrial pressure
Am J Physiol (Heart Circ Physiol)
Left ventricular volumes and hemodynamic responses to postexercise ischemia in healthy humans
Med Sci Sports Exerc
Severe exercise alters the strength and mechanisms of the muscle metaboreflex
Am J Physiol (Heart Circ Physiol)
Effects of metabolism and anesthesia on pulmonary ventilation
J Appl Physiol
Reflexes from the limbs as a factor in the hyperpnea of muscular exercise
Am J Physiol
Cardiac acceleration in man elicited by a muscle–heart reflex
J Appl Physiol
Cited by (67)
Recent advances in exercise pressor reflex function in health and disease
2020, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :Thus, these findings suggest that the mechanoreflex plays a significant role in mediating the exaggerated exercise pressor reflex in HF. Conversely, several studies by Piepoli and colleagues suggest that the metaboreflex primarily mediates the exaggerated exercise pressor reflex in HF (Piepoli et al., 1996, 1999, 2008; Scott et al., 2000). For example, Scott et al. (2000) showed an exaggerated ventilatory response to dynamic leg exercise with circulatory occlusion but not to passive exercise.
Expanding the clinical classification of heart failure: Inclusion of cardiac function during exercise
2018, Lifestyle in Heart Health and DiseaseNeurological Regulation of the Circulation
2017, Encyclopedia of Cardiovascular Research and MedicinePotential beneficial effect of some adipokines positively correlated with the adipose tissue content on the cardiovascular system
2016, International Journal of CardiologyCitation Excerpt :These disturbances are related not only to the cardiovascular system, but also to other systems which participate in modulation of its function, such as the immune system [2], the endocrine system [3], and the autonomic nervous system. [4] Heart failure contributes to the development of compensatory mechanisms which aim to preserve the function of other organs; however they finally contribute to improper regulation of their function and progression of heart failure. [1] One of these mechanisms is hyperactivation of the sympathetic nervous system and vasoconstriction –an example may constitute organs exhibiting high oxygen demand, such as skeletal muscles; oxygen supply during exertion in state of heart failure is an effect of hyperactivation of the sympathetic nervous system and vasoconstriction, without normal increase of cardiac output, what results in reduction of stroke volume. [4]