U.S. patent number 3,676,553 [Application Number 04/885,295] was granted by the patent office on 1972-07-11 for therapeutic composition.
This patent grant is currently assigned to Cybersol, Inc.. Invention is credited to Beverly L. Reynolds.
United States Patent |
3,676,553 |
Reynolds |
July 11, 1972 |
THERAPEUTIC COMPOSITION
Abstract
A therapeutic composition comprised of an aqueous medium
containing about 75-150 millimoles of Na.sup.+, about 5-50
millimoles of K.sup.+, about 5-50 millimoles of HCO.sub.3 .sup.-,
about 75-150 millimoles of Cl.sup.- and preferably containing about
1-30 millimoles of Mg.sup.+.sup.+ and about 1-30 millimoles of
HPO.sub.4.sup.-.sup.- and/or SO.sub.4.sup.-.sup.- ; the solution
having a pH of about 6.8-8.2 and an osmolality of about 170-460 and
preferably about 260-340 and more preferably 290-310. The solution
can be administered orally but preferably parenterally. Also, the
anhydrous form of the composition in a tablet form as well as an
oral composition containing flavoring agents is taught.
Inventors: |
Reynolds; Beverly L. (Dallas,
TX) |
Assignee: |
Cybersol, Inc. (Dallas,
TX)
|
Family
ID: |
25386579 |
Appl.
No.: |
04/885,295 |
Filed: |
December 15, 1969 |
Current U.S.
Class: |
424/601; 424/682;
424/679; 424/709 |
Current CPC
Class: |
A61K
33/00 (20130101); A61K 33/42 (20130101); A61K
33/16 (20130101); A61K 33/42 (20130101); A61K
33/42 (20130101); A61K 33/00 (20130101); A61K
33/06 (20130101); A61K 33/10 (20130101); A61K
2300/00 (20130101); A61K 33/04 (20130101); A61K
33/14 (20130101); A61K 33/14 (20130101); A61K
33/06 (20130101); A61K 33/00 (20130101); A61K
33/10 (20130101) |
Current International
Class: |
A61K
33/00 (20060101); A61K 33/42 (20060101); A61k
027/00 () |
Field of
Search: |
;424/128,153,180,154,162 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Friedman; Stanley J.
Claims
What is claimed is:
1. An injectable acqueous solution comprising about 75 to about 150
millimoles of sodium cation, about 5 to about 50 millimoles of
potassium cation, about 5 to about 50 millimoles of bicarbonate
anion and about 75 to about 150 millimoles of chloride anion and
having a pH of about 6.8 to about 8.2 and an osmolality of about
290 to about 310.
2. The composition of claim 1 wherein the pH is about 7.4 to about
8.0.
3. The composition of claim 1 wherein the osmolality is about
300.
4. The composition of claim 1 wherein about 1 to about 30
millimoles of magnesium cation and from about 1 to about 30
millimoles of phosphate and/or sulfate anion are incorporated into
the composition.
5. The aqueous solution of claim 1 wherein there is incorporated
about 1 to about 30 millimoles of magnesium cation.
6. The aqueous solution of claim 1 wherein there is incorporated
about 1 to about 30 millimoles of phosphate anion or sulfate anion
or a combination of phosphate and sulfate anions.
7. The aqueous solution of claim 1 wherein the osmolality is about
300.
8. The aqueous solution of claim 1 wherein the pH of the solution
is about 7.4 to about 8.0.
9. An injectable aqueous solution comprised of about 85 to about
140 millimoles of sodium cation, about 10 to about 40 millimoles of
potassium cation, about 2 to about 20 millimoles of magnesium
cation, about 85 to about 130 millimoles of chloride anion, about
10 to about 40 millimoles of bicarbonate anion and about 2 to about
20 millimoles of phosphate and/or sulfate anion(s) and the solution
having a pH within the range of about 6.8 to about 8.2 and having
an osmolality within the range of about 290 to about 310.
10. The aqueous solution of claim 9 wherein the pH is within the
range of about 7.4 to about 8.0.
11. An injectable aqueous solution comprised of about 103
millimoles of sodium chloride, about 25 millimoles of sodium
bicarbonate, about 17 millimoles of potassium chloride, and about 5
millimoles of magnesium sulfate and having a pH within the range of
about 7.6 to about 7.8.
Description
BACKGROUND OF THE INVENTION
After accidental or elective operative injury to human patients,
there occurs a decrease in the hemoglobin concentration, an
elevation of the erythrocyte sedimentation rate of peripheral
blood, and a loss of red blood cells (RBC) from the effective blood
volume. These events are recognized as anemia. Also, immediately
subsequent to the injury the white cell count is usually elevated,
and the thrombocyte count is decreased, implicating pancytic
mechanisms.
The administration of whole blood is useful to rectify the pancytic
changes. However, most surgeons have been unable to maintain
adequate quantities of peripheral total hemoglobin, red blood
cells, and thrombocytes through the use of whole blood, even when
quantities far in excess of that lost by bleeding are infused.
Also, the collection and storage of whole blood generally produces
a hyperosmolar, acidic water solution, as a result of the changes
in RBC and blood water during collection and storage. Furthermore,
whole blood is expensive, and may produce unwanted
immunohematological responses in the recipient.
The surgeon and anesthesiologist generally have four other choices,
i.e., instead of whole blood infusion, to correct these
adversities. These are administration of (1) plasma, (2) separated
(packed) erythrocytes, (3) synthetic water solutions, or (4)
synthetic water solutions containing synthetic protein. Plasma has
some of the disadvantages of whole blood. Separated erythrocytes,
besides being expensive, have the disadvantage of decreases in
functional and structural life after reinfusion. In recent years,
synthetic water solutions, with or without protein, have been used
to re-establish normalcy in peripheral vascular volumes and for
maintenance of blood pressure.
The development of synthetic water solutions in the prior art has
emphasized ionic content, particular sodium chloride, with little
regard to other physicochemical requirements. Such thinking is
still current. The most recently introduced water solutions beg
their use through ionic contents equivalent to plasma water as the
latter appears during health. Also, the blood water of patients,
receiving a multitude of new anesthetic agents and adjuvants and
subjected to operative techniques of increasing complexity, is
exposed to body water infusates which are at variance, frequently
extreme, with the physicochemical content in health.
Altering ionic content of water solutions has not provided the
water environment considered optimal during elective or traumatic
operative therapy. Furthermore, synthetic water solutions should
provide support to the patient in excess of maintenance of blood
water volume. Water for injection, sterile, U.S.P., may be used to
replace or expand blood water lost during elective or accidental
trauma, if the sole purpose of administered water solution is the
replacement of water losses. However, the anemia or injury is more
intense in the post-operative period after use of sterile water or
of other similar hypo-osmolar solutions, resulting in prolonged
morbidity, particularly in post-operative hospital time, and
accounting for the more frequent use of whole blood before, during,
and after operation.
The addition of sodium chloride to sterile water, in so-called
isotonic concentration (154 mEq/L [milliequivalents/liter]), has
reduced only minimally the post-operative anemia. Such a solution
has enhanced water retention significantly, as evidenced by
consistent gain in weight during operation when saline is
administered. Complimenting normal saline solutions with potassium
and calcium in concentrations equivalent to plasma water (10 mEq/L,
total) has had little additional effect. Hence, the addition of
ions to sterile water in quality and at concentrations
approximately those in blood water has not significantly reduced
anemias observed from the use of sterile water alone.
Examples of parenterally administrable preparations in current use
are: ##SPC1##
Certain of these solutions are compared in specific tests with
applicant's aqueous solution.
SUMMARY OF THE INVENTION
Applicant has discovered a therapeutic composition, preferably
administered parenterally, to overcome at least most of the
disadvantages of similar aqueous solutions in the prior art. The
formulation is based on the mean solute values in extracellular
water (referred to herein as ECW) and is designed to minimize water
movements into fixed cells after operative, anesthetic and
accidental trauma. Also, Applicant's parenteral solution diminishes
loss of functional decrements in all body systems, particularly
heart and circulating fluids, lung, kidney, gastrointestinal tract
and brain. Applicant's composition is useful in tablet form, oral
dosage form containing flavoring agent, etc.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Applicant's therapeutic composition is preferably iso-osmolar with
respect to the mean osmolality of ECW. The mobility of the ions is
preferably maximal in the ECW to minimize ICW (intracellular water)
depletion or overload. Also, the water content is preferably
representative of the ratio of water to solute loss during the
operative procedure or trauma or imbalance.
In extracellular water, the major cations are H.sup.+, K.sup.+,
Na.sup.+, Ca.sup.+.sup.+, and Mg.sup.+.sup.+ whereas the major
anions are OH.sup.-, HCO.sub.3 .sup.-, Cl.sup.-, SO.sub.4
.sup.-.sup.-, HPO.sub.4 .sup.-.sup.-, and IOA ("impermeable"
organic anions). The relative size of the hydrated ions, as
referenced to K.sup.+, and the velocity of each ion in water, in a
uniform electrical field, are:
Velocity of solute ion under gradient of one Relative diameter
Solute Solute volt/cm (univalent ion) of solute ion, cation anion
or 0.5 volt/cm (divalent) Angstroms
__________________________________________________________________________
H.sup.+ 315 0.20 K.sup.+ 64.2 1.00 Na.sup.+ 43.2 1.49 OH.sup.- 173
0.37 HCO.sub.3.sup.- 133 0.72 Cl.sup.- 65.2 0.98 IOA 35 1.84
SO.sub.4.sup.- .sup.- 34 1.89 HPO.sub.4.sup.- .sup.- 28 2.29
Ca.sup.+.sup.+ 25.5 2.51 Mg.sup.+.sup.+ 22.5 2.84
__________________________________________________________________________
The mobility coefficient of each ion in dilute water solution is
dependent upon the size of the hydrated ion and upon its velocity
under a uniform electrical gradient. Changes in solute content, pH,
and osmolality affect the mobility coefficients. The
Mg.sup.+.sup.+, HPO.sub.4 .sup.-.sup.- and SO.sub.4 .sup.-.sup.-
ions are implicated as components of intercellular water or
interstitial water substrates during glycolysis and oxidative
reaction sequences in energy metabolism.
Applicant's parenteral solution contains sodium (Na.sup.+) and
potassium (K.sup.+) as the principal major cation solutes, and
bicarbonate (HCO.sub.3 .sup.-) and chloride (Cl.sup.-) as the
primary anion solutes. These were selected because their
coefficients of mobility, with hydrogen (H.sup.+) and hydroxyl
(OH.sup.-), are maximal with respect to all other solutes, in any
given situation. Magnesium (Mg.sup.+.sup.+) was selected as the
principal minor solute cation, and phosphate
(HPO.sub.4.sup.-.sup.-) and/or sulfate (SO.sub.4 .sup.-.sup.-) as
the principal minor solute cation. The Mg.sup.+.sup.+, HPO.sub.4
.sup.-.sup.- and SO.sub.4 .sup.-.sup.- ions assist in stabilization
of solute velocities, hence distribution, in the extracellular
water and/or the intercellular water. The concentration of the ions
in applicant's aqueous solution are given in millimoles as:
Min- Max- Pre- Most Ion imum imum ferred Preferred
__________________________________________________________________________
Sodium (Na.sup.+) 75 150 85-140 128 Potassium (K.sup.+) 5 50 10-40
17 Magnesium (Mg.sup.+.sup.+) 1 30 2-20 5 Phosphate
(HPO.sub.4.sup.- .sup.-) or 1 30 2-20 5 Sulfate (SO.sub.4.sup.-
.sup.-) Bicarbonate (HCO.sub.3.sup.-) 5 50 10-40 25 Chloride
(Cl.sup.-) 75 150 85-130 120
__________________________________________________________________________
The administrable solution can have an osmolality (defined as the
specific number of millimoles dissolved in one liter of water)
within the range of from about 170 to about 460, preferably from
260 to 340, more preferably from 290 to 310 and most preferably
about 300. The pH can range from about 6.8 to 8.2 and preferably is
within the range of 7.4 to 8.0 and more preferably about 7.6 to
about 7.8. It is not necessary that the Mg.sup.+.sup.+, SO.sub.4
.sup.-.sup.-, and HPO.sub.4 .sup.-.sup.- be present but it is
preferred where stabilization of solute velocities, thus
distribution, is desired in the ECW and/or ICW. Known water soluble
salts containing the above ions are useful to make up the solution
in U.S.P. water. Examples of such salts include NaCl, KCl,
NaHCO.sub.3, KHCO.sub.3, MgCl.sub.2, Na.sub.2 SO.sub.4, Na.sub.2
HPO.sub.4, MgSO.sub.4, and K.sub.2 HPO.sub.4.
A preferred composition for parenteral administration is one
containing about 25 millimoles of NaHCO.sub.3, about 17 millimoles
of KCl, about 103 millimoles of NaCl and about 5 millimoles of
MgSO.sub.4.
Solutions having an osmolality less than about 290 can be designed
to move into the cells; thus, such solutions are useful in
treatment of heat stroke or situations causing excessive sweating.
However, if the osmolality desired is in excess of about 310, the
solution can be designed to attract water out of the cells. As a
result, such solutions are useful, for example, in the treatment of
overdoses of barbiturates or any situation resulting in an unusual
accumulation of water within the cells.
The pH of the solution is desirably about 6.8 to about 8.2. Such pH
is preferably obtained by using the appropriate salts taught within
this invention and such solution will be highly buffered against pH
changes. Adjustment of the pH can be obtained, if desired, with
known acids or bases, e.g., HCL, NaOH, etc. whose reactions with
the solution will not produce ion solutes different from those
specified.
The solution is preferably administered parenterally; but, it can
be administered orally. Where oral administration is desired, the
salt components are desirably chosen to eliminate objectionable
taste of the solution. For example, KCl can impart a bad taste. A
more acceptable solution from the standpoint of taste is one
containing KHCO.sub.3, NaHCO.sub.3, MgCl.sub.2, and Na.sub.2
SO.sub.4. Flavoring agents, e.g., orange flavoring, etc. and
pharmaceutically acceptable vitamins in dosage form compatible with
applicant's composition can be incorporated. For example, vitamin C
is useful where the solution is taken orally. Other additives
pharmaceutically acceptable and compatible with applicant's
composition can also be incorporated.
Also, the appropriate amount of cations and anions can be contained
in the anhydrous form as well as a concentrated hydrous form. The
hydrous form can be at a concentration more than the desired
osmolality and, before administration, it can be diluted to the
desired osmolality. By containing the solution at a high ion
concentration, shipping charges, storage costs, etc. can be
reduced.
Regarding the anhydrous form, the appropriate salts and the desired
amounts of salts can be contained in a protective container (a
pharmaceutically acceptable container) so that convenient dilution
to the desired volume and at the desired place of usage can be
obtained. Also, the salts can be compressed in a uniform mixture
and can optionally contain an inert diluent, e.g., binder. Thus,
the salts can be embodied in a tablet suitable for dilution and
eventually oral administration.
The tablet binder is a pharmaceutically acceptable binder and is
preferably one that produces minimum osmotic effects and is one
that is not ionized. Examples of useful binders include nonionic
detergents such as Pluronic F-68 (trademark of Wyandotte Chemicals
Corp., defined as a condensate of ethylene oxide with a condensate
of propylene oxide and propylene glycol) and similar nonionic
detergents, preferably having molecular weights above about 8,000.
Also, the tablet can contain pharmaceutically acceptable
effervescent agents such as citric acid, tartic acid, etc. Where
the salts are in the anhydrous form, the concentration of the ions
can be (mole %):
Preferred Most Ion Range Range Preferred Range
__________________________________________________________________________
Na.sup.+ 46.3-32.6 44.0-35.9 42.7 K.sup.+ 3.1-10.9 5.2-10.1 5.7
Mg.sup.+.sup.+ .6-6.5 1.0-5.1 1.7 HPO.sub.4.sup.-.sup.- or
SO.sub.4.sup.- .sup.- .6-6.5 1.0-5.1 1.7 HCO.sub.3.sup.- 3.1-10.9
5.2-10.1 8.3 Cl.sup.- 46.3-32.6 44.0-33.4 40.0
__________________________________________________________________________
Where the Mg.sup.+.sup.+ and HPO.sub.4 .sup.-.sup.- and/or SO.sub.4
.sup.-.sup.- ions are absent, the molar composition can be about
37.5-46.9% Na.sup.+, about 3.1-12.5% K.sup.+, about 3.1-12.5%
HCO.sub.3 .sup.-, and about 46.9-37.5% Cl.sup.-. But, preferably,
the Mg.sup.+.sup.+ and HPO.sub.4 .sup.-.sup.- and/or SO.sub.4
.sup.-.sup.- are present.
Applicant's solution is preferably administered to mammals before
operation, during anesthesia, during operation and after operation
or trauma. Desirably, it is administered in quantities calculated
to replace water and osmolar losses in the ECW. Excessive
administration of the solution can be tolerated by the mammal,
however, over-expansion of the ECW can modify moble cell
mobilization. Preferably, the solution is administered before
trauma and in amounts calculated to replace water and osmolar
losses in the ECW. Where administered before operation and before
anesthesia, it is preferably begun about 2 hours prior to
anesthesia.
Proper administering of applicant's solution, inter alia, can have
the following benefits:
1. iso-osmolar expansion of ECW with predictable equilibration of
administered water between circulating water volume and ISW space
components of ECW;
2. as a result of (1), a high tolerance of unplanned overloading of
the circulating water volume--thus hypertension, cardiac pulmonary
failure and coma can be reduced;
3. as a result of (1), maintenance of suspension indices of
solutes, e.g., mobile cells, lipids, and proteins, in ECW is
obtained;
4. as a result of (1) and (3), iso-osmolar expansion of large
solutes in ECW is obtained;
5. as a result of (4), minimization of mobile cell destruction
(particularly red cell) and of intravascular aggregation of cells
is obtained--both of which otherwise follow planned or unplanned
trauma;
6. as a result of (1), enhancement of perfusion of tissues during
elective, operative, and anesthetic trauma, with or without prior
accidental trauma, is reduced.
Other benefits are obvious after the specification and claims are
read and fully understood.
The following examples are presented merely to teach specific
working embodiments of the invention. Equivalents and uses, obvious
to those skilled in the art, are intended to be incorporated within
the invention as defined in the specification and appended
claims.
EXAMPLE
Mongrel canines having a mean weight of 15 kgm were operated on
under pentobarbital sodium anesthesia for bilateral placement of
ligatures about the renal pelvi and/or for splenectomy. Seven days
after operation, these animals were exposed to either water loading
or water deprivation test, as indicated below. The aoric blood
pressure, the hematocrit (HCT), blood water volume (B1W), and
extracellular water volume (ECW) were determined before and after
either loading or deprivation, and at indicated times. Where a
control patient is used, neither loading nor deprivation was
effected and a lapse of time equal to the same lapse for either
loading or deprivation was allowed for the after determination.
Where loading experiments were done, 30 minutes was allowed between
the determinations. In depletion experiments, determinations were
made immediately after hemorrhage, at 2 hours past hemorrhage, and
at 5 days past hemorrhage. The B1W was measured with T-1824 dye,
also defined as Evans blue dye; 30 minutes was allowed for
equilibration of the dye. HCT was determined from multiple arterial
and venous microhematocrit determinations (corrected for trapped
plasma) and was related to the true or "total body" hematocrit by
the ratio 0.85--this ratio was empirically measured by comparing
direct red cell volume and blood water measurements in 25 canines.
Red cell mass (RBC) was calculated from the hematocrit and blood
water volume. ECW was measured with radiobromium, Br-82, 2 hours
was allowed for equilibration of the isotope. Interstitial water
(ISW) was determined as the difference between ECW and TBV.
Osmolality was determined by commercial osmometer. Specific
gravities of all water solutions either added or removed were
determined, thus specific correlations were established between the
weight of either added or removed fluids. The partial pressure of
water vapor in the ambient air was adjusted to the partial pressure
of water vapor in the expired air of the animal under evaluation.
During loading, the ligatures were tightened about the renal pelvi.
Therefore, after the 30 minute interval for distribution of added
water solutions, during the 2 hours allowed for equilibration of
isotope and 30 minutes for equilibration of the dye, water losses
from the animals were minimized.
All solutions were prepared on the day of use after careful
weighing of dried reagents and addition of sterile water for
injection, U.S.P., to 1,000 milliliters. Sterilization was
accomplished by autoclave, after which a 5-milliliter aliquot of
each was removed and analyzed for solute content, osmolality, pH
and sterility. After evaluation, ligatures were removed, incisions
closed, and animals returned to their cages.
Deprivation Tests
Fifteen canines to each of five series were observed during water
deprivation of the ECW by hemorrhage at 47 percent of the TBV. In
one series, no replacement water solution was administered, and, as
reported in Table I, no animals survived 24 hours; these animals
expiring secondary to cardiac and pulmonary arrest. In four
additional series, Applicant's solution (U.S.P. water containing 25
millimoles of NaHCO.sub.3, 17 millimoles of KCL, 103 millimoles of
NaCl and 5 millimoles of MgSO.sub.4, osmolality = 300 pH = 7.6-7.8)
and certain other water solutions were infused singly into the
canines at the onset of ventricular fibrillation and cardiac
arrest. The infused quantities were equal to the shed blood volume.
Survival was 100 percent in animals receiving applicant's solution,
with a mobilization of an additional 16 percent of RBC. Survival
was reduced markedly in all animals receiving other water
solutions. Regarding other water solutions, enhancement of TBV was
best with sodium chloride, but pH and RBC decreases contributed to
low survival. Similarly, pH and RBC alterations by other water
solutions decreased survival. Furthermore, there is no statistical
difference between animals receiving either no water replacement or
either lactated Ringer's solution or Normosol-R. These results are
reported in Table I.
TABLE I
Comparison of applicant's solution with other water solutions (all
values 1 hour after replacement of water solution equal to shed
blood volume) ##SPC2##
Effect of Varying Osmolalities of Applicant's Solution During Water
Deprivation
Table II indicates the effect of varying the osmolality of
applicant's solutions (pH = 6.8-8.2) upon the mortality of canines
after water deprivation through hemorrhage of 47 percent of steady
state TBV. A 47 percent hemorrhage was sufficient to produce death
in 100 percent of the canines in the absence of injection of
parenteral fluids. The replacement of applicant's solution is equal
to shed blood:
TABLE II
Osmolality of in- Mor- RBC Mass after infusion fused solution
tality Percent of a TBV after (millimoles/liter) percent 47%
Hemorrhage
__________________________________________________________________________
460 15 -10 340 15 -10 310 Zero + 4.0 300 Zero +15 290 Zero + 2.5
260 25 .+-. 1.5 170 25 - 7
__________________________________________________________________________
The above data clearly indicates basis for preferred osmolality
ranges, especially the 290-310 range.
Establishment of pH Range
Five canines to each of 10 series were observed during separate
water deprivation tests of hemorrhage of 47 percent of TBV. The
exact quantity of shed TBV was replaced at the onset of cardiac
arrest with sodium chloride and sodium bicarbonate mixtures at pH
in range of from 5.5 to 8.8 although these solutions are not the
same as applicant's solution, these data obtained are applicable
with their invention. The critical pH established with minimum
mortality, i.e., no mortality, is from 6.8 to 8.2.
Water Loading
Each of 15 canines in three different series were observed during
water loading with (1) aqueous solutions of sodium chloride, (2)
aqueous solutions of sodium bicarbonate and (3) applicant's aqueous
solution containing 25 millimoles of NaHCO.sub.3, 17 millimoles of
KCl, 103 millimoles of NaCl and 5 millimoles of MgSO.sub.4. The
mean ECW of the canine = 3,000 ml. Results of the tests are given
in Table III: ##SPC3##
The above data indicate that with applicant's solution the ECW was
expanded by the same increment as the load and there was neither an
increase nor decrease in osmolality. Also, the RBC component of TBV
was increased by same percentage as was the ECW, hence BIW was
expanded in identical manner, 20 percent, such that TBV was
increased 20 percent.
Comparison with Other Water Solutions During Loading
Applicant's solution was compared with other water solutions at 30
minutes after canine water loading. The loading was equal to 100
percent of TBV. Data are presented in Table IV: ##SPC4##
The above data indicate that with sodium chloride, the RBC was
reduced 17 percent, and 20 percent of the canines expired. The
other solutions produced no mortality, however, each produced
dislocations of water and solutes and reduction in RBC as compared
to applicant's solution (identified in "Water Loading" tests,
osmolality = 300).
Effect on Blood Pressure With Applicant's Solution
During water loading and water deprivation tests, the effect on the
aortic and femoral blood pressures were observed. Results of these
tests are indicated in Table V. Applicant's aqueous solution is
identical to the one identified in "Water-Loading" tests.
TABLE V
Condition Blood Pressure Blood Pressure BIW Increase (%) Decrease
(%) Increase Aortic Femoral Aortic Femoral (%)
__________________________________________________________________________
Water loading (% of TBV) 10 2.3 1 25 20 3 8 11 30 8 15 35 Water
Depri- vation (% of TBV through hemorrhage) 10 2.0 2 20 3 12.25 4
30 5.0 60 9.5 35 7.0 77 10 47 9.3 99 18
__________________________________________________________________________
Loading at Different Osmolalities and pH
Loading of ECW with applicant's solution at different osmolalities
and pH was effected. The loading was equal to 100 percent of TBV.
The infused solutions contain Na.sup.+, K.sup.+, Cl.sup.- and
HCO.sub.3 .sup.- as the primary components and Mg.sup.+.sup.+,
HPO.sub.4 .sup.-.sup.- and SO.sub.4 .sup.-.sup.- as minor
components (3-10 millimoles) at the indicated osmolalities and pH.
Results are indicated in Table VI:
TABLE VI
Osmolality % % Change Per Cent (mO/L) pH ECW in RBC Mortality
__________________________________________________________________________
300 7.8 +22.5 +22 Zero 6.8 +21 +12 Zero 170 7.6 +11 0 Zero 6.8 + 9
- 3 Zero 260 7.8 +15 + 5 Zero 6.8 +13.5 0 Zero 290 7.8 +20 +10 Zero
6.8 +19 + 3 Zero 310 7.8 +26 + 8 Zero 6.8 +28 + 2 Zero 340 7.8 +34
0 Zero 6.8 +40 - 5 Zero 460 7.8 +40 - 5 Zero 6.8 +57 -10 Zero
__________________________________________________________________________
* * * * *