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Anesthesia May Work By Blocking Oxygen
Biophysicists in New York may be close to solving the riddle of
how general anesthetics actually
work.
Researchers Maoxin Wu and Huping Hu suggest anesthetics act as
barriers to oxygen transport inboth membranes and proteins,
reducing oxygen availability to the brain. Their mechanism may lead
tobetter, safer anesthetics, a revolution in the treatment of pain
and a more complete understanding of
the effects of alcohol on brain function.
Wu and Hu, both pathologists, are with Mount Sinai Medical
Center, New York, and Biophysics
Consulting Group, Old Bethpage, New York, respectively.
Although more than 150 years have past since the discovery of
general anesthetics, how theyprecisely work remains a mystery.
While scientists know general anesthetics affect a variety of
neurotransmitter receptors, a universally accepted mechanism of
anesthesia remains elusive.
Two schools of thought have existed until now:
-- The "lipid theory" proposes that anesthetics interact
directly with cell membranes that are involved
in brain functions.
-- The "protein theory" suggests that anesthetics directly
interact with cell proteins such as the ion
channels and receptors that are involved in
neurotransmission.
Neither concept is supported by direct experimental evidence,
however. Wu and Hu, on the otherhand, speculate that general
anesthetics perturb the pathways of oxygen, the most essential
component of brain function, in both cellular membranes and
cellular proteins.
When the brain detects oxygen deprivation, or hypoxia, it
immediately reduces its workload. Part ofthis workload is sensing
pain. Wu and Hu claim that anesthesia, then, is a byproduct of the
brain's own
self-preservation mechanism.
Wu and Hu predict further research could formulate better
anesthetics that more effectively blockoxygen pathways by enhancing
their ability to be absorbed by the fatty membranes that serve
asoxygen gateways. For example, anesthetics with shorter
hydrocarbon chains would be more effectivethan anesthetics with
longer-chain hydrocarbons because the membranes that control oxygen
uptake
in the brain more easily absorb them.
Additionally, alcohol's intoxicating effects may result from
disruption of oxygen pathways in the brain,and many side effects of
general anesthetics, including some well-known but poorly
understoodtoxicities, may be explained by the proposed mechanism.
Short-chain hydrocarbon anesthetics, for
instance, have fewer and less toxic side effects and they are
better oxygen blocks.
Dr. Judith Tharp, a chief clinician with the Federal Bureau of
Prisons, expressed fascination with theresults. "There's no
question that a mechanism such as the one proposed by Drs. Wu and
Hu couldresult in the formulation of better anesthetics, simply by
defining their exact targets more precisely," she
said. "It is true -- we still don't know exactly what we are
aiming for with general anesthesia."--Copyright 2001 by United
Press International.
All rights reserved.
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