Slow Waves in Health and Disease
- Motility disorders of the gastrointestinal tract increase with aging and inflammatory conditions; constipation and faecal incontinence are the most common symptoms in the elderly.
- Several control systems are responsible for the regulation of normal transit of contents through the gastrointestinal tract. One of the most important involves local reflexes controlled by the enteric nervous system.
- Whilst the enteric nervous system plays a major role in peristalsis, the frequency and propagation characteristics of peristaltic activity under normal conditions are governed by intrinsic, omnipresent, electrical membrane-potential oscillations often referred to as pacemaker activity or ‘slow waves’.
- These slow waves are readily visible on an electrogastrogram (EGG) and have been used for diagnostic purposes in patients with dyspepsia, motility disorders or unexplained nausea and vomiting.
- Interstitial cells of Cajal (ICC) generate the slow waves and appear to act as an intermediate between the enteric nervous system and smooth muscle cells.
- We are interested mechanisms of drug-induced dysrhythmia leading to nausea and vomiting, and also in the changes in the control of slow waves during neurodegenerative diseases.
Radiotelemetric Recordings of the Electrogastrogram
We use radiotelemetric recording techniques to record gastric slow waves in the mouse, Suncus murinus and ferret.
The approach involves the surgical implantation of radiotransmitters capable of recording gastric myoelectric signals (sampled at 1 kHz), and electronic filtering in several steps to remove cardiac and respiratory signals, as well as low frequency artifacts such as movement. Data can then be computed on successive sections of recordings to reveal the dominant power (DP, the highest power in recorded range); ii) the dominant frequency (DF, frequency bin with the highest power in the range); iii) the DF instability coefficient (DFIC, defined as the standard deviation of the DF divided by its mean, over a 10 min period). We can then look at the duration of effects of drug action during our experiments, and also correlate the information with changes in blood pressure and temperature (also measured telemetrically), and also with behavioural changes including emesis, modification of feeding and drinking, and locomotor activity. We are in the process of advancing our technology to be able to simultaneously record respiratory function by whole body plethysmography during the acquisition of radiotelemetric data.
The approach involves the surgical implantation of radiotransmitters capable of recording gastric myoelectric signals (sampled at 1 kHz), and electronic filtering in several steps to remove cardiac and respiratory signals, as well as low frequency artifacts such as movement. Data can then be computed on successive sections of recordings to reveal the dominant power (DP, the highest power in recorded range); ii) the dominant frequency (DF, frequency bin with the highest power in the range); iii) the DF instability coefficient (DFIC, defined as the standard deviation of the DF divided by its mean, over a 10 min period). We can then look at the duration of effects of drug action during our experiments, and also correlate the information with changes in blood pressure and temperature (also measured telemetrically), and also with behavioural changes including emesis, modification of feeding and drinking, and locomotor activity. We are in the process of advancing our technology to be able to simultaneously record respiratory function by whole body plethysmography during the acquisition of radiotelemetric data.
Pacemaker Potentials of the Microeletrode Array
We use the microelectrode array (MEA) to record gastrointestinal (GI) slow waves using isolated stomach and intestinal tissues from the mouse, Suncus murinus and ferret. This approach allows high-throughput screening of drug effects on GI slow waves through incubating target drugs with isolated GI tissues. Our MEA systems allow simultaneously recordings from 60-electrode on a chip under a controlled temperature environment. With 60-channel data, apart from deriving the basic slow wave features, such as dominant frequency and power, signal amplitudes and periods, we can further look into the propagation velocity and activation time pattern across the chip. We are developing automatic programs using MATLAB platform for data analysis to pick up all possible slow wave features from 60-channel raw traces. We are interested in applying this approach in large-scale drug screening to build a database for machine learning on drug-induced gut dysrhythmia. Read more...