The Testing

Group photo!!!

Phil doing an endothelial function test on Mike Jim, Kate and Sam running a sympathetic blockade test on Dougie (see the neck chamber on him)
Phil, bracing (fearing for his life) himself for a TMS from Emma

1 April - 6 April

We’re officially half way through our testing, as well as our stay here at the Pyramid Laboratory. I am pleased to say that everything is running smoothly…. despite my absence for the last 3 nights. For those of you concerned, I was sent down to lower altitude since I suffered from a nasty combination of acute mountain sickness and pneumonia, and was not recovering as well as our doctors hoped. (NB This was due to my stupidity in trying to keep up with Jim on a "brisk hike" on our supposed rest day.) Anyway, after 3 nights I’m back to make up for the lost time. (And we certainly plan to put Mickey to work to make up for his many missed shifts over the past week! (Kate))

Unfortunately, my return also coincided with the departure of Sam, Hamish, Dougie, and Robin who left us after just a week at the Pyramid. Their contributions to the experiments and of course the life and spirit of the lodge were invaluable. Their presence will be sorely missed (and the place will certainly be a lot quieter without them around).

When any of our party have been free from the experiments (and the weather allowed) there have been many day trips and exploratory walks of the area. Steve and Bruce made it to Everest Base Camp (although were quite disappointed with what they found – rocks and tents apparently!) and stayed the night in Gorak Shep to allow easier access to a sunrise at Kala Patthar (5545m), which sounded unbelievable. Sam, Hamish and Joe followed suit and had a sunrise walk up Kala Patthar too, and many more of us are hoping to do the same before our time here is up. Today Emma, Kelly and Mike have ventured off to Base Camp despite the constant snow that’s been falling at the Pyramid – let’s hope the weather held out for them! So there’s plenty to see and do when the experimental schedule allows.

THE EXPERIMENTS!

Well the lack of discussion about experiments really reflects that most folk involved in running the experiments have been working 12-16 hr days so no time to write about them. Now, we have about 5 days of testing left and, thankfully, are almost through most of the work. So what have we done, and why? The details of each experiment would take too long to describe, so we will keep the overview brief. But, without question, due to the sophisticated equipment, the invasive interventions, the large amount of volunteers (including high altitude sherpas) we have managed (if all continues to go well over the next week) to conduct some of the most detailed experiments about breathing, vascular health, brain blood flow and sleep at high altitude.


Ventilatory control and abnormal breathing during sleep.

This experiment involves giving participants drugs which either increase or decrease their brain blood flow and we study how this affects their control of breathing by getting them to breathe various gas mixtures (high O2 & high CO2, low O2 & high CO2, low O2) from a closed bag.

Following the ventilatory response tests before and after drug administration, the participants are set up with numerous electrodes and wires to monitor their sleeping patterns throughout the night (making you look like robots from the future). The results of these experiments will tell us the mechanisms (i.e. ventilatory control and brain blood flow changes) by which abnormal breathing occurs during sleep – the same changes occur in people with heart failure and typically occur just before people die. Experimental studies at high altitude provide the perfect ‘model’ to study these changes without the confounding influence of disease.

Sympathetic blockade

One notable thing which occurs at high altitude is a large increase in the sympathetic nervous system activity; this elevates heart rate, amongst other things. It is also possible that such sympathetic changes have a profound effect on breathing, vascular health, brain blood flow. To examine whether this is the case or not, we need to effectively ‘block’ such elevations in sympathetic nerve activity.

To do this, in Dunedin and at 5050 m we administer drugs (specifically alpha and beta blockers) to our volunteers to inhibit the sympathetic nervous system. Kelly had a particularly severe response to the blockade, her symptoms included: feeling very sleepy, loss of (voluntary) movement in her legs, fainting, severely hypotensive (which resulted in her been carried feet first up the stairs!!!), complete loss of colour in her face, looking like she was on her death bed, and a very vague recollection of the whole event.


Following the drug administration, we conduct a series of tests which include:

1) An ultrasound scan of the brachial artery to measure the ability of the artery to dilate following forearm occlusion (by inflating a cuff around your forearm).

2) Putting on a neck chamber which alters the pressure surrounding the neck to measure the body's control of blood pressure.

3) Blowing against a closed tube to measure the blood pressure responsiveness.

4) Breathing a various mixtures of gases (high O2 & high CO2, low O2 & high CO2, low O2) in a closed bag to investigate the control of breathing (it feels particularly uncomfortable as the bag starts to empty and you begin to feel like you're suffocating).

Endothelial function and arterial stiffness experiments

It is known that patients who are exposed to low levels of oxygen (like we are experiencing at high altitude) tend to have a reduced endothelial function, stiffer arteries and tend to die much sooner that otherwise healthy people. People born and bred at high altitude also die much sooner than low-landers, but it is not clear why this occurs. The hypoxia at high altitude may reduce endothelial function and elevate arterial stiffness, making them much more prone to cardiovascular events and early death. For the first time, these experiments assess whether high altitude residents, and newcomers to high altitude (i.e. us) might have alterations in endothelial function and arterial stiffness.

To do this, we examine how stiff the arterial walls are and their ability to dilate in response to a shear stress response, oral administrations of nitric oxide, and the potential ways in which changes can be altered by inspiring 100% O2 at high altitude. We do this by measuring changes in blood vessel diameter and velocity and the arterial stiffness of the carotid (neck), brachial (arm), and femoral (inner thigh) arteries using special Doppler and pulse-wave velocity probes.

Neuromuscular tests

This study looks at the functioning of the brain to muscle pathway of the quadricpes muscles and the respiratory muscles (in partcular the diaphragm). It uses a technique called transcranial magnetic stimulation, which involves placing a magnetic coil over the part of the subject's brain which controls muscle contraction, and discharging a stimulation which causes an involuntary muscle contraction in the muscles under investigation. The response is recorded by electromyography and as the force produced by that muscle during the contraction. By doing stimulation before and after a fatiguing exercise it is possible to understand more about how the brain communicates with the muscles when they are fatigued, and how this communication changes during environmental stress such as hypoxia.

The contrast between control of the limb muscles and the respiratory muscles is interesting, as the respiratory muscles have to work harder than usual all the time we are at altitude, as we increase our ventilation in response to the hypoxia. This may change the brain muscle relationship in a different way than in the limb muscles. The stimulation technique is painless (it doesn't activate any pain receptors at all) - however some of the group have identified the transcranial stimulation as their least favourite test (see Phil in the photo!!) - but this testing hasn't made anyone feel ill yet - the same can't quite be said for all the other testing....... (this is Emma defending her study!!!)

Only five days to go….

Phil, Kate and Mickey