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Steroids and oxygen solubility
307 STEROIDS AND OXYGEN SOLUBILITY James V. Gainer, Jr., Kingwood,’ West Virginia
M.D.
26537
John L. Gainer, Ph.D. and Robert Kelly, B.S. Department of Chemical Engineering, University of Virginia Charlottesville, Virginia 22.901 Received: b/2/76 ABSTRACT Determinations of oxygen solubility in serum were made utilizing vari#ous concentrations of corticosteroids in the serum. Within a certain concentration range dexamethasone and betUmQthasOnQ caused an None of the other steroids tssted incrlease in oxygen solubi 1i ty. demonstrated this propertyIN77RODUCTION The use of corticosteroids largely to for
on a trial
treat
many divsrse
;them are well
desired
effects
anisms of use
their
and side
effects have
We recently
investigated of oxygen
factors
for
~QVQ~ of
ation,
it
oxygen
in plasrm
seemed that
yet
is
steroids
of Since
instant
and function important might
However,
indications of
the
the mech-
delineated,
and their
(1).
the effect in serum.
rate
understanding
been WQll
empirica
at any given
the metabolic
a number of
has developed.
not
is still
on the solubility
to a tissue
and a bQttQr
has developed
drugs have been utilized
At present
conditions.
actions
medicine
and these
basis,
established,
in many instances
available
in clinical
and error
some of
these
is one of of
the
some effect
oxygen
the determining
tissue
in dQtQm2ining exert
compounds
the amount of
(2)
tissue
and the oxygen-
on oxygen
availability. METHOD Lyophi2ized humun serum ~0s reconstituted and placed in a stand&d 100 cc. laboratory beaker. A small aliguot of an antifoaming agent* WQS placed in it to prevent frothing. Preliminary tests were done to show that the sotubility of oxygen in sQrum was identical to that in plasma. Also, testing indicated that the antifoaming agent had no effect on the oxygen solubility in serum. Oxygen of 9% purity was then bubbled into the solution for a period of ten minutes to allow the solution to bscome fully saturated. Samples were taken with special airtight syringes and injected into a gas chromatograph for determination of the oxygen content of the sample, using a method previously described by Navarri (3). The apparatus used MS a Beckman Gc2A thermal conductivity machine fitted with a molecular The samples injQCtQd first passed through a drying tube sieve column.
VoZwntz 28, Number 3
S
-Z?ClilROIDCJ
September,
2976
containing calcium sulfate in order to remove the liquid from the sample. Preliminary tests showed that the gases were not absorbed in this section, but passed directly into the gas chromatograph. An integrating recorder was used to provide direct mQ:surements of the oxygen solubility. The procedures pre done at 25 C., and the temperature was maintained within 1 of this leval throughout the testing. Following QStabliShmQnt of the normal oxygen solubility level, a similar procedure was performed on serum samples containing various concentrations of steroids. The values rsported are relative to the normal oxygen solubility ~QVQ~ and are exprsssed as a percentage incrQasQ or dQCreaSQ in oxygen solubilitu. Each test w&S rapeated a number of times and the values obtained were within a % range. RESULTS Testing
was done with
ignated
by their
article),
were
trivial
several
names
cortisone*,
steroids.
These
(IVPAC nomenclature
compounds, given
cOrtiSOl*, prQdnisolonQ*,
des-
following
methylprednisolone:
dexamethasone*, and betanzethasone*. Of the compounds tested, only dexamethasone and betamethasone (Figure 1).
caused an increase in oxygen solubility
The ma,jor increases occurred in a concentration range of
0.5 - 4.0 micrograms/milliliter
for dexamethasone and 0.625 - 5.0
micrograms/millilitslr for betamethasone. 507; Change in 0 Solu 2.zlity
-IO- , 0 05
2
3
4
6
IO
I 40
I 100
Dexamethasone Concentration (fig/ml of SQrU d W 'l/o Change in 0 Solu a*zlity
IO 5 0 0.625 2.5 DetamQthasonQ Concentration (ug/ml of Serum)
Figure 1.
Oxygen Solubility with Dexamethasone
20
and Detamethsone
S The other (Figure
steroids
all
used in clinical
309
caused a decrease
The concentrations
2).
those
tested
TIIEOXDI
of
the drugs
in oxygen
solubility
used were similar
to
medicine.
% Change in 0 Solu 6 ility -3ot 0
,
,
,
,
I
IO
25
50
Cortisone (j&ml
-301
, 0
2.5
,
,
,
5
IO
40
uncertain
caused an increase resemblance (4)
transport
to
the organic
and thus
support
curve, only
the steroids data,
are obviously irmnediately
small oxygen
Whether
needed for
have clinical
effect
this
We have sur-
but have no data solubility
significance
on the oxygenation
in viva
metabolic
in the plasma,
It
the same gas
in oxygen
determination.
significance.
in serum.
do (5). case,
have any clinical
oxygen for
is available
normally in this
the changes
such as the
usable
amount which should
tested
solubility
can perform
occurs
some
which are known to carry
oxygen
erythrocytes
mechanism
contention.
known and other
ftuorocarbons, increase
and betamethasone
These compounds bear
solubility.
fluorochemicals
which
a similar
this with
occur
should that
functions
that
80
Concentration of Serum)
as to why dexamethasone in oxygen
has been suggested
mised
,
with Cortisone and Prednisolone Oxygen Solubility* 2. *(Similar decreases in the solubility of oxygen were also obtained with hydrocortisone and methylprednisolone)
We are
oxygen
, 200
Concentration QfSerum)
Prednisolone (us/ml Figure
, 100
that
is not saturation
However,
since
processes
is
a change
to
in total
the the
plasmuz
310 REFEREN(Z&S I. 2. 3.
4. 5.
Long Dfl, Maxwelt RF, French LA: Staroids and Brain Edema- Edited by HJ Reulen, K Sch&man. NQW York,?&=,?!?!, p !%‘-% Beischer DE: Man’s DependQnce on ths Earthy New York,Taxl lan, by K i%b~Q~. Systemsttt Ph,D. Nuvarri RPI: “Mass Transport in Biological Dissertion, &tversity of Virgtnia, ChartOttQsVftle, ytrginia Geger RP: -FQd Proe 29:1?58-1763, Z970, J. Appt PhusioZ 27,666Z, Sloviter, HA st al:
1969,
Antt-foamtng agent: Antt-Foamw - A, Dow Corning BQtamQthasonQ: BetamethasQnQ sodium phosphate, CQlQstone@, $~Iuoro-~1~,17,2~-trihydroxy-I68-mQthyl-l,6-prQgnadieno-~,20dione, Schsring Cortisone acstatca, Upjohn Cortisone: DQxamQthasonQsodium phosphate, Dscadron @, DQxamethasone: $~1uoro-lIa,17,21-trihy~oxg-j!6a-nzathyl-l,4-pregnadiene-J,20dione, Merck Sharps and Do&e Cort 2.901: Hgdrocortisone sodium succinate, SoZu Corte $ , Upjohn HethyLprQ ‘so tons: ~Qth~~pre~is~~one sodium succtnate, So&E%dro 9 138,17,21-trihydroxg-6a-msthyl-1,4-pregnadienQ~3,~ dions, ~pjo~ PrQdnZsolone: PrQ~~s~lonQ sodfun suceinata, MetieortQ~~ne @I, IZLB,2?,2l-trihydroxg-f,~-prczgnadSene-J,X)-dtono, Sehering
M.D.
26537
John L. Gainer, Ph.D. and Robert Kelly, B.S. Department of Chemical Engineering, University of Virginia Charlottesville, Virginia 22.901 Received: b/2/76 ABSTRACT Determinations of oxygen solubility in serum were made utilizing vari#ous concentrations of corticosteroids in the serum. Within a certain concentration range dexamethasone and betUmQthasOnQ caused an None of the other steroids tssted incrlease in oxygen solubi 1i ty. demonstrated this propertyIN77RODUCTION The use of corticosteroids largely to for
on a trial
treat
many divsrse
;them are well
desired
effects
anisms of use
their
and side
effects have
We recently
investigated of oxygen
factors
for
~QVQ~ of
ation,
it
oxygen
in plasrm
seemed that
yet
is
steroids
of Since
instant
and function important might
However,
indications of
the
the mech-
delineated,
and their
(1).
the effect in serum.
rate
understanding
been WQll
empirica
at any given
the metabolic
a number of
has developed.
not
is still
on the solubility
to a tissue
and a bQttQr
has developed
drugs have been utilized
At present
conditions.
actions
medicine
and these
basis,
established,
in many instances
available
in clinical
and error
some of
these
is one of of
the
some effect
oxygen
the determining
tissue
in dQtQm2ining exert
compounds
the amount of
(2)
tissue
and the oxygen-
on oxygen
availability. METHOD Lyophi2ized humun serum ~0s reconstituted and placed in a stand&d 100 cc. laboratory beaker. A small aliguot of an antifoaming agent* WQS placed in it to prevent frothing. Preliminary tests were done to show that the sotubility of oxygen in sQrum was identical to that in plasma. Also, testing indicated that the antifoaming agent had no effect on the oxygen solubility in serum. Oxygen of 9% purity was then bubbled into the solution for a period of ten minutes to allow the solution to bscome fully saturated. Samples were taken with special airtight syringes and injected into a gas chromatograph for determination of the oxygen content of the sample, using a method previously described by Navarri (3). The apparatus used MS a Beckman Gc2A thermal conductivity machine fitted with a molecular The samples injQCtQd first passed through a drying tube sieve column.
VoZwntz 28, Number 3
S
-Z?ClilROIDCJ
September,
2976
containing calcium sulfate in order to remove the liquid from the sample. Preliminary tests showed that the gases were not absorbed in this section, but passed directly into the gas chromatograph. An integrating recorder was used to provide direct mQ:surements of the oxygen solubility. The procedures pre done at 25 C., and the temperature was maintained within 1 of this leval throughout the testing. Following QStabliShmQnt of the normal oxygen solubility level, a similar procedure was performed on serum samples containing various concentrations of steroids. The values rsported are relative to the normal oxygen solubility ~QVQ~ and are exprsssed as a percentage incrQasQ or dQCreaSQ in oxygen solubilitu. Each test w&S rapeated a number of times and the values obtained were within a % range. RESULTS Testing
was done with
ignated
by their
article),
were
trivial
several
names
cortisone*,
steroids.
These
(IVPAC nomenclature
compounds, given
cOrtiSOl*, prQdnisolonQ*,
des-
following
methylprednisolone:
dexamethasone*, and betanzethasone*. Of the compounds tested, only dexamethasone and betamethasone (Figure 1).
caused an increase in oxygen solubility
The ma,jor increases occurred in a concentration range of
0.5 - 4.0 micrograms/milliliter
for dexamethasone and 0.625 - 5.0
micrograms/millilitslr for betamethasone. 507; Change in 0 Solu 2.zlity
-IO- , 0 05
2
3
4
6
IO
I 40
I 100
Dexamethasone Concentration (fig/ml of SQrU d W 'l/o Change in 0 Solu a*zlity
IO 5 0 0.625 2.5 DetamQthasonQ Concentration (ug/ml of Serum)
Figure 1.
Oxygen Solubility with Dexamethasone
20
and Detamethsone
S The other (Figure
steroids
all
used in clinical
309
caused a decrease
The concentrations
2).
those
tested
TIIEOXDI
of
the drugs
in oxygen
solubility
used were similar
to
medicine.
% Change in 0 Solu 6 ility -3ot 0
,
,
,
,
I
IO
25
50
Cortisone (j&ml
-301
, 0
2.5
,
,
,
5
IO
40
uncertain
caused an increase resemblance (4)
transport
to
the organic
and thus
support
curve, only
the steroids data,
are obviously irmnediately
small oxygen
Whether
needed for
have clinical
effect
this
We have sur-
but have no data solubility
significance
on the oxygenation
in viva
metabolic
in the plasma,
It
the same gas
in oxygen
determination.
significance.
in serum.
do (5). case,
have any clinical
oxygen for
is available
normally in this
the changes
such as the
usable
amount which should
tested
solubility
can perform
occurs
some
which are known to carry
oxygen
erythrocytes
mechanism
contention.
known and other
ftuorocarbons, increase
and betamethasone
These compounds bear
solubility.
fluorochemicals
which
a similar
this with
occur
should that
functions
that
80
Concentration of Serum)
as to why dexamethasone in oxygen
has been suggested
mised
,
with Cortisone and Prednisolone Oxygen Solubility* 2. *(Similar decreases in the solubility of oxygen were also obtained with hydrocortisone and methylprednisolone)
We are
oxygen
, 200
Concentration QfSerum)
Prednisolone (us/ml Figure
, 100
that
is not saturation
However,
since
processes
is
a change
to
in total
the the
plasmuz
310 REFEREN(Z&S I. 2. 3.
4. 5.
Long Dfl, Maxwelt RF, French LA: Staroids and Brain Edema- Edited by HJ Reulen, K Sch&man. NQW York,?&=,?!?!, p !%‘-% Beischer DE: Man’s DependQnce on ths Earthy New York,Taxl lan, by K i%b~Q~. Systemsttt Ph,D. Nuvarri RPI: “Mass Transport in Biological Dissertion, &tversity of Virgtnia, ChartOttQsVftle, ytrginia Geger RP: -FQd Proe 29:1?58-1763, Z970, J. Appt PhusioZ 27,666Z, Sloviter, HA st al:
1969,
Antt-foamtng agent: Antt-Foamw - A, Dow Corning BQtamQthasonQ: BetamethasQnQ sodium phosphate, CQlQstone@, $~Iuoro-~1~,17,2~-trihydroxy-I68-mQthyl-l,6-prQgnadieno-~,20dione, Schsring Cortisone acstatca, Upjohn Cortisone: DQxamQthasonQsodium phosphate, Dscadron @, DQxamethasone: $~1uoro-lIa,17,21-trihy~oxg-j!6a-nzathyl-l,4-pregnadiene-J,20dione, Merck Sharps and Do&e Cort 2.901: Hgdrocortisone sodium succinate, SoZu Corte $ , Upjohn HethyLprQ ‘so tons: ~Qth~~pre~is~~one sodium succtnate, So&E%dro 9 138,17,21-trihydroxg-6a-msthyl-1,4-pregnadienQ~3,~ dions, ~pjo~ PrQdnZsolone: PrQ~~s~lonQ sodfun suceinata, MetieortQ~~ne @I, IZLB,2?,2l-trihydroxg-f,~-prczgnadSene-J,X)-dtono, Sehering