As we mentioned in a previous post, Ged and Vicky recently attended The Physiological Society‘s conference in Cardiff. One of the great things about going to scientific conferences is that it gives you an opportunity to see what research other people are doing, often in areas quite different to your own. One of the other researchers at Physiology 2015 was Andrew O’Leary, who is working towards his PhD in the Physiology Department at University College Cork in Ireland, under the supervision of Professor Ken O’Halloran. He has been working on some research examining the effect of low oxygen levels on breathing muscles, but using mice instead of people. We thought you might be interested to hear about his work and why we thought Irish mice could be useful in our own.
We know that when people get certain types of breathing problems, particularly those severe enough to require Intensive Care Unit (ICU) admission, they often suffer from very low oxygen levels (called ‘hypoxia’). We don’t really know at present what hypoxia over a long period of time does to the respiratory muscles. In this study, Andrew took two groups of mice and made one group breath air containing only 10% oxygen for up to 8 hours. The other group breathed normal air (21% oxygen). The amount of air the mice breathed in and out throughout the experiment was recorded constantly by placing the mice in a special measurement chamber. At the end of the experiment, the mice were humanely killed and their respiratory muscles were carefully measured in a number of ways.
The first interesting thing is that the mice in the hypoxic gas breathed a bit faster and deeper to start with (this is what humans would do – increasing the amount of air going in and out of the lungs in order to try and compensate for the lower availability of oxygen) but then went back to their normal breathing after about 20 minutes. Mice are a bit different to humans in that they can reduce their metabolic rate so that their body doesn’t require as much oxygen, like hibernating animals, so this is probably why their breathing rate and depth went back to normal despite the lower oxygen levels.
The respiratory muscles (the diaphragm and a muscle in the neck called the sternohyoid) were weaker in the hypoxic mice at the end of the experiment, with the diaphragms in the hypoxic mice only able to generate 70% of the force of the diaphragms from the control mice. Other tests that Andrew did showed that genes in the respiratory muscles were behaving differently in the hypoxic mice’s muscles. The changes in these genes suggested that the mitochondria (the ‘battery packs’ in cells) were not as efficient at generating energy for muscle contractions, and that the cells may have been releasing less calcium (which is used by the ‘contractile machinery’ of the muscle cells) to help the muscle produce force.
While obviously what happens in mice might be very different to what happens in people, we were still very interested in Andrew’s findings. We have known for a long time that people who are on ICU get weakness in their breathing muscles, and that this is often due to the fact that these patients spend long periods of time on a ventilator. This means that their breathing muscles don’t have to do much or any work, and so can waste away – a bit like someone’s leg if they break it and it’s put in a plaster cast. What Andrew’s work might suggest, though, is that the initial illness that causes people’s oxygen levels to drop might also play a part in the weakness developing. What’s really useful about doing animal research is that you can get a much more detailed picture about how all of the different aspects of muscle function are affected by the hypoxia – it wouldn’t be possible to make all of these measurements in people, and in a patient group there would be a large number of other factors that might be influencing any changes seen. We think this is a great example of how different types of research can complement one another to move the scientific field forward. Thanks to Andrew O’Leary and his supervisor Prof O’Halloran for allowing us to write about their research – and for the really fascinating discussion that we had at his poster during the conference. Watch this space for more Irish mouse news in future perhaps!