Although it’s not a part of the body most readily linked to ME/CFS, there is plenty of evidence showing that the heart, blood vessels and autonomic nervous system (which controls the heart) are affected in people with the disease.
Some of the first research supported by ME Research UK more than twenty years ago concerned blood vessel function, and we have continued to fund many projects investigating this area.
In this series of two articles, Dr Eleanor Roberts describes the heart and circulation, how they deliver oxygen and nutrients around the body, and what aspects may be abnormal in people with ME/CFS.
The heart is responsible for pumping blood throughout our network of blood vessels, to deliver oxygen and nutrients around the body, and to collect the waste products of metabolism.
In humans, the heart is divided into four chambers, with the left and right atria at the top, and the left and right ventricles at the bottom.
When physical workload increases (as we exercise, for example), there is usually a corresponding increase in the heart rate so that the amount of oxygenated blood pumped out by the heart can match the higher demands. Heart rate can be measured at different conditions to help understand how a person functions during exertion.
There are a number of other measurements that are important when assessing the function of the heart. These include:
- Cardiac output, which is the volume of blood pumped by the heart in 1 minute;
- Cardiac index, which relates the cardiac output to the size of the individual;
- Stroke volume, which is the amount of blood pumped by the heart with each beat;
- Oxygen uptake (VO2), which is the amount of oxygen consumed in 1 minute (VO2 max is the maximum amount of oxygen that can be consumed during exercise);
- End-diastolic volume, which is the volume of blood in the ventricles when filled.
Doctors and researchers use a number of different methods to assess the heart and circulation. These include:
- Cardiopulmonary exercise testing, which measures the change in heart rate during exercise;
- Tilt table test, which assesses how a person’s blood pressure and heart rate respond to gravity while lying on a bed that is slowly tilted upward;
- Heart rate variability, which is how the heart rate fluctuates over time depending on activity;
- Brain natriuretic protein, which is secreted by the heart ventricles when the muscle cells are overstretched, and is used as a measure of heart failure.
The autonomic nervous system
The autonomic nervous system (ANS) regulates the body’s unconscious actions such as digestion, respiration, urination, and of course the heart. It comprises the sympathetic nervous system (involved in energy mobilisation), the parasympathetic nervous system (vegetative and restorative functions) and the enteric nervous system.
The ANS plays a key role in relaying signals from the central nervous system to a number of body organs and processes. This includes the heart and circulation, where the ANS regulates heart rate and the force of each heart contraction, as well as blood vessel constriction and dilation (which controls how much blood is flowing).
The heart contains sinoatrial (SA) and atrioventricular (AV) node cells. The SA cells are the ‘pacemaker’ cells of the heart, located in the wall of the right atrium. They usually discharge at a rate of around 100 beats per minute, although this can be regulated by the parasympathetic nervous system (via the neurotransmitter acetylcholine.
The SA and AV nodes, along with heart muscle tissue (myocardium) and the electrical conduction system of the heart, are also supplied by sympathetic-nervous-system fibres, and activated by release of the hormone adrenaline (also known as epinephrine).
The largest nerves in the ANS are the right and left vagus nerves. These nerves supply numerous body systems and organs including the intestines, heart and some skeletal muscles. In the heart, the vagus nerve is involved in lowering heart rate via the SA node.
Measurement of heart rate and blood pressure variability can be a reflection of the balance between the sympathetic and parasympathetic nervous systems. Sympathetic and adrenal activity is usually increased by exercise, while there is reduced parasympathetic output in times of perceived danger.
During sleep, neural activity alternates between predominantly sympathetic and parasympathetic activity. Sympathetic activity is reduced when someone goes from being awake to being asleep, and is at its lowest during deep sleep, and vice versa for parasympathetic activity. Activity between the two states can be measured via analysis of heart-rate variability, which is usually greatest when going from wakefulness to sleep onset and in slow wave sleep, and lowest during rapid eye movement ‘dream’ sleep.
The blood vessels
Most blood vessels are formed of three layers of cells, with the endothelium forming the innermost layer, muscles cells and elastic fibres in the middle, and collagen-containing cells housing nerve endings making up the outer layer (or adventitia).
Blood vessels may also house immune system cells called macrophages. How extensive each layer is depends on whether they are forming an artery or a vein, and whether it is a large (over 1 cm in diameter) or small vessel (down to 4 mm).
Blood vessels are supplied by the sympathetic nervous system, which can cause constriction and is involved in increasing blood pressure and modulating blood flow. The parasympathetic nervous system is involved in dilating blood vessels that lead to the gastrointestinal tract and increasing blood flow.
The endothelial cells in most blood vessels are tightly adjacent to each other, but they can separate due to the actions of chemical signals from cytokines in response to stress or inflammation. This can allow molecules usually contained within the blood vessel (including metabolic waste) to leak out into the extravascular space surrounding the blood vessel.
Read part 2 of this article, in which Eleanor looks at some of the research studies showing how the heart and circulation may be involved in some of the symptoms of ME/CFS.