Abnormal Breathing Research in the Himalayas

Two weeks of research at 5050 m above sea level

Earlier this year, a group of scientists and clinicians led by Dr Phil Ainslie from Otago University, took part in a research project investigating abnormal periodic breathing. The experiments were conducted at sea level as well as in the Pyramid Research Laboratory on K2, Himalaya Mountains at 5050 m.

Left: Dr Phil Ainslie and the Pyramid Lab amongst its 5050 m spectacular setting in the Himalaya Mountains. Right: The Pyramid Research Lab and the study participants.

Abnormal periodic breathing occurs in heart failure patients and characteristically precedes death. It is also present during sleep at high altitude, making the location of the Pyramid Research Laboratory ideal as it nullifies the confounding influence of cardiovascular disease. The aim of the study was to examine the mechanisms by which abnormal breathing develops at high altitude using sleep monitoring and brain blood flow imaging techniques with pharmacological intervention.

Four Experiment Groups:

Four types of experiments were carried out in the Pyramid Research Lab over 14 days. Two rooms were set up as laboratories and experiments were conducted simultaneously in both locations. As the use of the Pyramid Research Lab is highly sought by researchers around the world, the time allocated to Dr Phil Ainslie’s group was sure to be utilized to the maximum: research was carried almost 24/7 with both awake and asleep subjects.

1. Ventilatory Control and Abnormal Breathing During Sleep.
In this experiment participants were administered drugs to increase or decrease the flow of blood in the brain. The study investigated the effects of increased and decreased blood flow on the control of breathing by getting the individuals to breathe various gas mixtures that included:

• high O2 and high CO2
  
• low O2 and high CO2
  
• low O2
The study subjects were connected to a number of electrodes and sensors following the ventilatory tests before and after drug administration. The results of these experiments aim to shed light on the mechanisms by which abnormal breathing occurs during sleep.



Sleeping and ventilatory experiments during the day and night.




"The ADInstruments gear performed superbly! In our previous experience, and that of others, the actual measurements of end tidal gases and ventilation have been near on impossible to make above 4000 m. We spent almost over 2 weeks at 5050 m and basically turned the ADInstruments equipment on when we arrived and it ran almost continuously for the duration of the experiments, which were done during sleep in day and night time. We got all of our data." Dr Phil Ainslie

2. Sympathetic Blockade
A large increase in the sympathetic nervous system activity and an increased heart rate at high altitude are common phenomena. In order to examine whether such sympathetic changes have any major effects on breathing and brain blood flow, ‘blocking’ of the elevations in sympathetic nerve activity was necessary.

Sympathetic blockade tests using the Finometer Midi NIBP System and ADInstruments Metabolic System.

Volunteers were administered alpha and beta-blockers to inhibit the sympathetic nervous system. Following the drug administration, tests that were conducted included:


• An ultrasound scan of the brachial artery to measure the ability of the artery to dilate following forearm occlusion
  
• Using a neck chamber to alter the pressure surrounding the neck and measure the body's control of blood pressure
  
• Force breathing against a closed tube and recording blood pressure responsiveness
• Breathing various mixtures of gases in a closed bag to investigate the control of breathing
  


3. Endothelial Function and Arterial Stiffness Experiments
Individuals living at high-altitude, and patients exposed to low levels of oxygen, have a shorter life expectancy than people living at low altitude. They also have stiffer arteries and a reduced endothelial function. The hypothesis that hypoxia at high altitude may reduce endothelial function an increase the stiffness of arteries.

Left: Dr Phil Ainslie performing an endothelial function test. Right: A number of tests were carried out on the local population.

The experiments carried out on locals and visitors examined arterial stiffness and their ability to dilate following a shear stress response, orally administered nitric oxide and breathing in 100% O2 at high altitude. Changes in blood vessel diameter and velocity, arterial stiffness of the carotid, brachial and femoral arteries were recorded using Doppler and pulse-wave velocity probes.

4. Neuromuscular Tests
These tests looked at the relationship between the brain and muscle groups such as the quadriceps and the diaphragm. A magnetic coil was placed over the part of the brain that controls muscle contraction.

The discharges stimulation caused involuntary muscle contraction of the muscles under investigation and resulting EMG signals were recorded. The stimulation was performed before and after strenuous exercises to try to evaluate communication changes during environmental stress such as hypoxia.

Products used in the study that are manufactured and/or sold by ADInstruments ADInstruments PowerLab Data Acquisition Systems LabChart Software Finometer Midi NIBP System ADInstruments Gas Analyzer ADInstruments Spirometer ADInstruments Bio Amps Heated Pneumotach Pulse Oximeter Pod ADInstruments Metabolic System Respiratory Flowheads and Accessories

About Dr Phil Ainslie Dr Phil Ainslie has had a long interest in human cerebrovascular physiology and is a keen mountaineer. Phil graduated with a Masters in Science from King’s College, UK and received a PhD joint between Oxford, John Moore’s and Manchester Universities. He since has worked in UK, US, Canada and now New Zealand, developing various techniques to permit novel assessment of human cerebral vascular function. Currently he is a researcher and educator at the Department of Physiology, University of Otago, New Zealand.

27 October 2008