New pacemaker offers heart failure hope
A new pacemaker which synchronises heart rate with breathing could "revolutionise" the lives of people with heart failure, The Daily Telegraph reports.
Pacemakers are small electronic devices, implanted in the body, that help keep the heart beating regularly. They are normally used in people with conditions that disrupt the beating of the heart, such as sick sinus syndrome or heart block.
Current pacemakers actually make the heart beat "too regularly", as the healthy heart shows slight variations in rate, in terms of how it is synchronised with our breathing.
This latest research tested a more advanced form of pacemaker, known as an artificial central pattern generator (ACPG), that aims to restore the natural synchronisation of heart rate with breathing. The generator is designed to receive nerve signals from the diaphragm (a muscle used to expand and contract the lungs) and then transmit the signals to the vagus nerve, which controls heart rate.
The particular area of medical interest for the ACPG is slightly different from the current use of pacemakers. It is thought that the ACPG could be used in people with heart failure, while previous research has demonstrated that this natural synchronisation is lost in heart failure, and may be associated with poor health outcome.
The results of this early laboratory study were promising, with the technology able to coordinate a rat's heart rate with its breathing pattern.
Where did the story come from?
The study was carried out by researchers from the Universities of Bath and Bristol, and the University of São Paulo in Brazil. It was partly supported by the EPSRC (UK) – Higher Education Investment Fund.
The research was published in the peer-reviewed medical journal Journal of Neuroscience Methods.
The study was actually published back in 2013, but has hit the headlines now, as the British Heart Foundation has said it is to provide funding to allow the researchers to continue their analysis of ACPGs.
The Daily Telegraph’s reporting of the study is of a good quality and includes a discussion with experts, which generally view this new development in a positive light.
The associate medical director at the British Heart Foundation is quoted as saying that, “this study is a novel and exciting first step towards a new generation of smarter pacemakers. More and more people are living with heart failure, so our funding in this area is crucial. The work from this innovative research team could have a real impact on heart failure patients’ lives in the future”.
What kind of research was this?
This was laboratory research concerned with the design of a new pacemaker that is able to synchronise the heart rate with breathing pattern, as happens naturally.
Pacemakers are fitted in people that have conditions that disrupt the normal beating of the heart.
The researchers say that all mammals have what are called “central pattern generators” (CPGs). These contain small groups of nerve cells that regulate biological rhythms and coordinate motor rhythms, such as breathing, coughing and swallowing.
The CPG in the brainstem (the bottom part of the brain that connects to the spinal cord) is said to coordinate the heartbeat with our breathing pattern.
This phenomenon is said to be known as “respiratory sinus arrhythmia” (RSA) – an alteration in the normal heart rate that naturally occurs during our breathing cycle.
In people with heart failure (a disease process with many causes, where the heart is unable to pump enough blood to meet the body’s demands), RSA is lost, and this is said to be a prognostic indicator for poor outcome.
The aim of this latest study was to try and build an artificial (silicon) CPG that could generate these rhythms. It was then tested in rats, to see whether it was able to alter the rat’s heart rate during the respiratory cycle.
What did the research involve?
The researchers describe how they developed the artificial CPG in preparation for live testing in rats.
The laboratory process is complex, but essentially the rats were anaesthetised and their body systems artificially manipulated. The CPG was connected to the phrenic nerve, which supplies the diaphragm, and the vagus nerve, which controls automatic processes in various body organs, including the heart rate.
The CPG received signals from the phrenic nerve, which were then processed electronically in the CPG, to produce voltage oscillations that stimulated the vagus nerve to control the heart rate.
The researchers monitored the heart using an electrocardiogram (ECG). They also looked at what happened when they injected a chemical (sodium cyanide) to stimulate the respiratory rate via sensory receptors.
The artificial CPG circuit was designed so it could provide three-phase stimulation, stimulating the vagus nerve during inspiration, early expiration and late expiration.
What were the basic results?
In rats, the heart rate naturally oscillates in rhythm with respiration, to give a natural RSA with a period of 4.1 seconds, and an amplitude (changes in wavelength) of around 0.08Hz.
In the laboratory, using the artificial CPG, the artificial RSA varied depending on the timing of impulses during the breathing cycle. The artificial CPG had the strongest influence when the vagus nerve was stimulated during the first inspiratory phase. This caused the heart rate to roughly halve, from 4.8 to 2.5 beats per second. The researchers describe that the heart rate decline during stimulation was a decrease of around 3 beats each second. During recovery, following stimulation, the heart rate returned to its resting value at an increased rate of +1 beat each second.
The CPG had a similar effect when the vagus nerve was stimulated during the early expiratory phase, but less of an effect when stimulated during late expiration (with heart rate only decreasing at a rate of around 1 beat per second to between 2.5 and 4 beats per second, rather than 2.5).
When they used the chemical to stimulate respiration, they found that this caused an increased burst rate of phrenic nerve activity, such that there was an increased rate of stimulation to the vagus nerve, allowing less time for the heart rate to recover. The heart rate was still synchronised to the respiratory rate, but the voltage oscillations had weaker amplitude.
How did the researchers interpret the results?
The researchers conclude that their study shows neurostimulation using an ACPG can augment RSA (improve synchronisation between heart rate and breathing). They suggest this opens a new line of therapeutic possibilities for an artificial device that can restore RSA in people with cardiovascular conditions such as heart failure, where the synchronisation of heart rate with respiration has been lost.
Conclusion
This laboratory research describes the complex design and animal testing of an ACPG that aims to restore the natural synchronisation of the heart rate with the breathing pattern. Naturally in the body, our heart rate alters slightly as we breathe in and out (RSA).
In people with heart failure (a disease process with many causes, where the heart is unable to pump enough blood to meet the body’s demands), RSA is described as being "lost", and previous research has suggested this to be a prognostic indicator for poor outcome.
This research described the development of an ACPG and its testing in rats. The generator received incoming signals from the phrenic connected to the diaphragm, and then produced voltage oscillations that stimulated the vagus nerve, which controls heart rate.
The results were promising, demonstrating that the technology was able to coordinate the heart rate with breathing pattern. The heart rate varied, depending on the stage during breathing that the vagus nerve was stimulated.
When stimulated during the inspiratory phase, it decreased heart rate by around 50% of the normal rate, but had little effect on heart rate during the late expiratory phase.
Overall, this technique shows promise, but having only so far been tested in rats in the laboratory, it is far too early to tell if and when it will be developed for testing in humans and, importantly, whether it would actually have any effect on health outcomes.
