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Climbing With Dr John West in
the Rarefied Air of Pulmonary Research:
From Mount Everest to the University of California, San
Diego
 When
you have been recruited as a clinical investigator to
climb Mount Everest with Sir Edmund Hillary, have coauthored
427 articles and 21 books, one of which is still used
as a classic medical text translated into 13 languages,
what worlds are left to conquer? Quite a few, says John
West, MD, Distinguished Professor of Medicine and Physiology,
University of California, San Diego.
It was 45 years ago when he heard about an upcoming physiological
expedition to the Himalayas and, to his surprise, was
picked to join Griffith Pugh, an eminent British physiologist.
The Australian-born West and the team lived for several
months in a laboratory at 19,000 feet and made field measurements
of maximal exercise up to an altitude of 24,000 feet.
One of the critical questions to emerge from that expedition
was whether humans would be able to reach the summit of
Mount Everest without supplementary
oxygen. Although two European climbers proved that it
was possible, in 1981 Dr West led the American Medical
Research Expedition to Everest, recording physiological
measurements at unprecedented altitudes, including the
summit. The results showed that humans made “almost
incredible adaptations to this extremely hypoxic environment”
with a calculated arterial PO2 of about 30 torr, PCO2
of 7 to 8 torr, and PH of over 7.7.
Closer to home and down to earth at the University of
California, San Diego, Dr West has extended the direction
of research he pursued at the pinnacle of Everest. “I’m
still very interested in pulmonary hypertension from the
standpoint of what happens at a high altitude,” he
says. “And I’m interested in the work being
done on the fragility of pulmonary capillaries. We believe
that when you raise pressure in pulmonary capillaries
to either unphysiologically high levels or even to the
highest level that you get under normal physiological
conditions the wall of the capillaries is damaged in some
way.”
Dr West and his colleagues found that in elite athletes
who exercise at extremely high levels, changes apparently
occur in the capillary wall as evidenced by results of
bronchoalveolar lavage (BAL). After a period of heavy
exercise, these athletes have increased red blood cells
and higher protein concentrations in their BAL fluid than
do controls.
The Pulmonary Thromboendarterectomy (PTE) program at
UCSD is also a prime interest of Dr West. In patients
who have undergone a PTE, research has shown that in areas
where emboli have been removed, the capillaries have been
damaged. “You see local acute lung injury with the
high protein concentrations in the BAL fluid. I suspect
that this has to do with remodeling of the capillaries
that occurs when they are protected from the normal pressures
because of the embolus. When the embolus is removed, damage
may occur in the walls. However, that is very hypothetical.”
High Altitude and Pulmonary Hypertension
Considering his studies on high altitude, Dr West was
asked what implications could be drawn for patients with
pulmonary hypertension. “At high altitudes you get
hypoxic pulmonary vasoconstriction, constriction of small
pulmonary arteries as a result of low levels of oxygen
in the lung. That’s a reversible phenomenon. When
you come down (from a higher altitude) the pulmonary artery
pressure falls. It’s a different situation that is
found with primary pulmonary hypertension. People who
remain at high altitudes can develop remodeling in the
small arteries and then the pulmonary hypertension becomes
to some extent nonreversible. This was shown, for example,
in a study, Operation Everest 2, in 1985.”
In this study, he said, subjects were kept in a low pressure
chamber for a long period and they developed pulmonary
hypertension because of the alveolar hypoxia. They found
that after about 7 days when the subjects were administered
100% oxygen the pulmonary artery pressure did not return
to the sea level value, indicating that there was some
organic change, a structural change in the blood vessels
that is now referred to as remodeling. “Remodeling
is very rapid in the pulmonary circulation. Some people
think the pulmonary circulation moves rather slowly in
terms of histological changes but that is not true.”
He notes that an animal study by Tozzi, for example, of
pulmonary arteries showed changes in messenger RNA and
protein within 4 hours after rings from pulmonary arteries
were stretched. “Things happen very quickly when
you raise the pulmonary artery pressure.”
A Landmark Text and the Zones of West The impact of Dr
West’s work is still much in evidence as a new generation
of physicians prepares to enter practice. His landmark
text, Respiratory Physiology: the Essentials, is used
worldwide, including centers in Moscow and Beijing, and
has been translated into 13 languages. The Zones of West—a
three-zone model of blood flow in the lung—is part
of a paradigm used throughout the world. It originated
almost 50 years ago when Dr West and his colleagues encountered
radioactive oxygen, which has a very short half life.
“We were able to look at blood flow in the lung for
the first time and we found a very uneven distribution
from the top to the bottom of the lung. I spent several
years figuring out the reason for that and that’s
where the three-zone model comes from.”
Considering how his world has changed, Dr West reflects:
“It is sad to see how junior faculty in the intensive
care units sometimes founder when confronted with basic
questions about pulmonary gas exchange or mechanics. This
is because the fashion in research over the last 20 years
has very much been in molecular biology. I’m not
saying that is a bad thing because it is terribly exciting.
But, as a result, the interests of young physicians in
pulmonary medicine have moved away from pulmonary gas
exchange and pulmonary mechanisms. In fact, regrettably,
many of the young people are not as well informed in those
areas as they should be. And those areas are terribly
important in the ICU, where the immediate problems are
not molecular but have to do with maintaining adequate
gas exchange and ventilating the lung in an appropriate
way.
“It’s a bit of an irony that we have a whole
generation of young pulmonary physicians, but some of
them tend to be rather weak in what I regard as the fundamentals
of respiratory physiology.”
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