The role of the muscle metaboreflex in patients with chronic disease

Grieve, Douglas Andrew Alexander (2008) The role of the muscle metaboreflex in patients with chronic disease. MD thesis, University of Glasgow.

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Exercising muscle needs a constant supply of oxygen for the aerobic metabolism of carbohydrate and fat, and regulation of the blood supply to muscle during exercise is therefore critical. Heart rate, stroke volume and minute ventilation all increase during exercise, and sympathetic vasoconstriction diverts blood to exercising muscle. It is well recognised that receptors in skeletal muscle play a vital role in the regulation of blood flow, including receptors sensitive to products of anaerobic metabolism such as lactate and hydrogen ions: metaboreceptors. Activation of the muscle metaboreflex signals the need for an increase in blood flow, and leads to an increase in cardiac output, ventilation and sympathetic vasoconstriction to non-essential organs.

Exercise intolerance is one of the most disabling symptoms in patients with a range of cardiorespiratory diseases. Abnormalities of skeletal muscle favouring anaerobic metabolism have been documented in both chronic heart failure and chronic obstructive pulmonary disease (COPD), and this is thought to be relevant to exercise limitation in these diseases. Studies looking at patients with chronic heart failure have demonstrated an increase in muscle metaboreflex activity. It is thought that abnormal skeletal muscle generates greater quantities of anaerobic metabolites, leading to increased metaboreceptor activation. This in turn causes an increased sympathetic nervous system and ventilatory response to exercise. Patients with COPD have been shown to demonstrate similar skeletal muscle abnormalities, so we hypothesised that we would also find an increase in muscle metaboreflex activity in this group.

It is possible to quantify muscle metaboreflex activity by exercising a small muscle group to fatigue then isolating it from the rest of the circulation with a sphygmomanometer cuff. This traps the metabolic products of exercise in the muscle and leads to prolonged stimulation of metaboreceptors. This can be measured as a sustained increase in blood pressure and ventilation when compared with control recovery without cuff inflation.

The aims of this thesis were as follows: (i) to assess if it is possible to quantify the muscle metaboreflex in a group of patients with COPD and to determine whether muscle metaboreflex activity is increased in patients with more severe disease, (ii) to determine whether supplementation with oral creatine monohydrate alters muscle metaboreflex activity, upper limb strength or endurance and respiratory muscle strength in patients with COPD, (iii) to assess the effects of diabetic autonomic neuropathy on muscle metaboreflex function, and (iv) to evaluate whether pulse transit time is of use in the measurement of muscle metaboreflex activity.

In our first study, we looked at a group of patients with stable COPD and found that rhythmic forearm exercise followed by post-exercise forearm ischaemia led to a sustained increase in blood pressure and minute ventilation when compared with control recovery. These findings are in keeping with previously published observations in normal subjects and in patients with chronic heart failure. We found that there was no difference in muscle metaboreflex activity between the groups of patients with moderate or severe disease.

We then performed a randomised, double-blind, placebo-controlled, crossover trial looking at the effects of loading a group of patients with stable COPD with creatine monohydrate. We demonstrated a small increase in body weight and an increase in peak inspiratory and expiratory mouth pressures, but there were no effects on muscle metaboreflex activity or forearm muscle strength, endurance or recovery.

A group of patients with type I diabetes mellitus was then used to study the effects of autonomic neuropathy on muscle metaboreflex function. We found that there was no difference in metaboreflex activity between subjects with diabetic autonomic neuropathy and subjects with diabetes but no evidence of autonomic neuropathy, suggesting that the afferent and efferent limbs of the muscle metaboreflex were intact.

Our final study evaluated whether pulse transit time could be used to assess muscle metaboreflex activity. Pulse transit time is defined as the time taken for a pulse wave to travel between two arterial sites, and can be easily and non-invasively measured. It is thought to reflect blood pressure and arterial tone. In a group of healthy subjects, we found that pulse transit time fell with rhythmic handgrip exercise, and post-exercise muscle ischaemia led to a sustained fall in pulse transit time when compared with control recovery. Pulse transit time therefore shows promise in the measurement of muscle metaboreflex activity, but further studies are required. Studies comparing pulse transit time with more invasive measurements such as muscle sympathetic nerve activity would be of particular interest.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Metaboreflex, mataboreceptor, skeletal muscle, COPD.
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Q Science > QP Physiology
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: Lean, Professor M. E. J. and Cotton, Dr. Mark
Date of Award: 2008
Depositing User: Dr Douglas Grieve
Unique ID: glathesis:2008-414
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 05 Feb 2009
Last Modified: 10 Dec 2012 13:18

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