DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

560 of other gases, resulting in a mixture of much lower
density that is easier to breathe.
The primary uses of helium are in pulmonary
function testing, the treatment of respiratory obstruction,
laser airway surgery, as a label in imaging studies,
and for diving at depth. The determinations of
residual lung volume, functional residual capacity, and
related lung volumes require a highly diffusible nontoxic
gas that is insoluble and does not leave the lung by
the bloodstream so that, by dilution, the lung volume
can be measured. Helium is well suited to these needs.
A breath of a known concentration of helium is given,
and the concentration of helium is measured in the
mixed expired gas, allowing calculation of the other
pulmonary volumes.
SECTION II
NEUROPHARMACOLOGY
Pulmonary gas flow normally is laminar. With increased
flow rates or a narrowed flow pathway, a component of pulmonary
gas flow becomes turbulent. Helium can be added to oxygen to
reduce turbulence due to airway obstruction since the density of
helium is less than that of air and the viscosity of helium is greater
than that of air. Addition of helium reduces the Reynolds number of
the mixture (the Reynolds number is proportional to density and
inversely proportional to viscosity), thereby reducing turbulence.
Mixtures of helium and oxygen reduce the work of breathing. The
utility of helium/oxygen mixtures is limited by the fact that oxygenation
often accompanies airway obstruction. The need for
increased inspired O 2
concentration limits the fraction of helium
that can be used. Furthermore, even though helium reduces the
Reynolds number of the gas mixture, the viscosity of helium is
greater than that of air, and the increased viscosity increases the
resistance to flow according to Poiseuille’s law, whereby flow is
inversely proportional to viscosity.
Helium has high thermal conductivity, making it useful during
laser surgery on the airway. This more rapid conduction of heat
away from the point of contact of the laser beam reduces the spread
of tissue damage and the likelihood that the ignition point of flammable
materials in the airway will be reached. Its low density
improves the flow through the small endotracheal tubes typically
used in such procedures. However, its use for this purpose is rare.
Laser-polarized helium is used as an inhalational contrast
agent for pulmonary magnetic resonance imaging. Optical pumping
of hyperpolarized helium increases the signal from the gas in the
lung to permit detailed imaging of the airways and inspired airflow
patterns (Hopkins et al., 2007).
Hyperbaric Applications. The depth and duration of diving activity
are limited by oxygen toxicity, inert gas (nitrogen) narcosis, and
nitrogen supersaturation when decompressing. Oxygen toxicity is a
problem with prolonged exposure to compressed air at 500 kPa (5
atm) or more. This problem can be minimized by dilution of oxygen
with helium, which lacks narcotic potential even at very high pressures
and is quite insoluble in body tissues. This low solubility
reduces the likelihood of bubble formation after decompression,
which therefore can be achieved more rapidly. The low density of
helium also reduces the work of breathing in the otherwise dense
hyperbaric atmosphere. The lower heat capacity of helium also
decreases respiratory heat loss, which can be significant when diving
at depth.
HYDROGEN SULFIDE
Hydrogen sulfide (H 2
S), which has a characteristic rotten
egg smell, is a colorless, flammable, water-soluble
gas that is primarily considered a toxic agent due to its
ability to inhibit mitochondrial respiration through
blockade of cytochrome c oxidase. Recent research has
demonstrated that H 2
S in low quantities may have the
potential to limit cell death (Lefer, 2007). Inhibition of
respiration is potentially toxic; however, if depression
of respiration occurs in a controlled manner, it may
allow non-hibernating species exposed to inhaled H 2
S
to enter a state akin to suspended animation (i.e., a
slowing of cellular activity to a point where metabolic
processes are inhibited but not terminal) and thereby
increase tolerance to stress. H 2
S also may cause activation
of ATP-dependent K + channels, cause vasodilation
properties, and serve as a free radical scavenger. H 2
S
has been shown to protect against whole-body hypoxia,
lethal hemorrhage, and ischemia-reperfusion injury in
various organs including the kidney, lung, liver, and
heart. Currently, effort is underway for development of
gas-releasing molecules that could deliver H 2
S and
other therapeutic gases to diseased tissue (Bannenberg
and Vieira, 2009). Though H 2
S has clinical potential,
further verification in preclinical models is necessary
as is more information regarding the route of delivery,
timing, formulation, and concentration of H 2
S.
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