An Otago research expedition to the Himalayas to study the effects of high altitude on the human body could potentially lead to new, safe treatments for cardiovascular disease, including sleep apnoea.

Data are still being analysed, but preliminary results indicate that changes in blood flow to the brain play a crucial role in the development of abnormal breathing found in these health problems. Such breathing causes uncontrolled, potentially highly-dangerous increases and decreases in blood pressure and flow to the brain.

Results also suggest there is heightened activity in the body's sympathetic nervous system, causing profound changes in breathing, blood pressure and heart rate. In addition, there is a big reduction in vascular (artery and blood vessel) health at high altitude, with native Sherpas suffering long-term effects.

The multidisciplinary study involved a 20-strong team of staff and students from the University's Departments of Physiology, Medicine and Physical Education, and research collaborators from the UK and Australia. Nepalese high-altitude Sherpas also participated as research subjects. The research team, led by Physiology lecturer Dr Phil Ainslie, was based near Base Camp Everest at the Pyramid research laboratory which, at 5,050 metres, is the highest in the world. A series of experiments were conducted in Dunedin on team members before leaving and then repeated at Pyramid, so comparisons could be made between their effects at sea level and at high altitude.

14_philainslieOne group of experiments examined how breathing is controlled by the brain and how this might cause abnormal breathing during sleep. This involved using pharmacological agents that increased or decreased blood flow to the brain, and assessing how this affected breathing. Then, following tests to measure their sensitivity to oxygen and carbon dioxide, volunteers were set up with electrodes and wires to monitor their sleep patterns during the night. The aim was to discover the mechanisms (control of breathing and brain blood-flow changes) by which abnormal breathing (sleep apnoea) occurs during sleep.

Ainslie says it appears changes in individual sensitivity (responders and non-responders) to these gases are the main reasons people get abnormal breathing at high altitude, and in heart failure.

Preliminary results suggest changes in blood flow to the brain caused by these individual variations are crucial to the development of abnormal breathing.

"If we gave people drugs which increased flow to the brain, this reduced abnormal breathing by about 50 per cent whereas, in those who had the drug which reduced the flow, their abnormal breathing worsened."

This could be important in heart failure, sleep apnoea, strokes and hypertension because patients with a low blood flow to the brain might be much more prone to abnormal breathing.

Other experiments focused on sympathetic nervous system activity - known to increase at high altitude - and its relationship with vascular health, breathing and blood flow. This required blocking such activity using alpha and beta blockers.

"At high altitude, everyone who goes up there has an increase in sympathetic activity which we can block with drugs, so we can say these responses are or are not caused by sympathetic activity rather than by high altitude.

Preliminary results indicate that changes in blood flow to the brain play a crucial role in the development of abnormal breathing.

"Generally, the drugs reduced blood pressure and heart rate [normally elevated at high altitude] which highlights sympathetic activity actually causes a lot of effects up there. And vascular health seems to get much worse, but improves when drugs block sympathetic activity."

Further experiments examined whether there were changes in blood-vessel health and arterial stiffness caused by hypoxia - low pressure of oxygen in the body. This happens at high altitude due to a drop in barometric pressure and in many heart and lung disease patients, with an increased risk of heart attacks and strokes.

Ainslie says early results using techniques such as administering nitric oxide to dilate blood vessels indicate a big reduction in vascular health at high altitude. He adds that the Sherpas' poor blood-vessel health, the result of living at 5,000 metres, is likely the main reason why they tend to die 20 to 30 years earlier than people at low altitudes.

Final results from the study will be published in a series of papers late this year and in early 2009.

14_philainslie_basecampAinslie has applied for grants for further study into altering blood flow to the brain in different patient groups. This could potentially lead to safe drugs to prevent abnormal breathing which, he says, would improve cardiovascular health and reduce mortality.

Other drugs could block sympathetic activity, limiting the extent of changes in blood vessel function and arterial stiffness. "We're also looking at non-pharmacological interventions such as increasing physical activity, which can have a similar [beneficial] effect."

Funding