Review
Cardiovascular and ventilatory control during exercise in chronic heart failure: Role of muscle reflexes

https://doi.org/10.1016/j.ijcard.2008.02.030Get rights and content

Abstract

During exercise nervous signals are generated by stimulation of mechanically (muscle mechanoreflex) and chemically (muscle metaboreflex) sensitive skeletal muscle receptors. These receptors and their associated afferent fibres are sensitive to muscle work and reflexively adjust the haemodynamic, ventilatory and circulatory responses during physical effort. Thus the muscle reflex is essential in achieving normal responses to exercise in healthy subjects. In chronic heart failure, characterised by exercise intolerance with early occurrence of dyspnea or fatigue, peripheral muscle abnormalities (i.e. muscle atrophy, decreased peripheral blood flow, fibre-type transformation, and reduced oxidative capacity) trigger an exaggerated muscle reflex. This abnormality has recently been implicated in the genesis of the disabling symptoms. We review the role of the muscle reflex in regulating the cardiovascular and the ventilatory systems during exercise in both healthy and diseased conditions.

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

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