PACIFIC SOUTHWEST ASSOCIATION O F CHEMISTRY TEACHERS PLASMA EXPANDERS' ROBERT T. m R R I C K Don Baxter, Inc., Glendale, California
THE administration of blood or plasma to a patient in shock is a complex problem. We are all familiar with the elaborate precautions taken in the preparation and handling of our food. Yet, compare this t o the care necessary in preparing and handling a material which is to be injected directly into the blood stream of a patient.
Egg Albnnm
9z.m
p-LoctogIabulin ropm
0
m
Albuinin
Hemoglobin
69,000
68000
-
0.-Lipoprotein 200.000
-
Insulin 36.000
a- Globulin 90,000
(
y- Globul~n
156.000
4- Lipoprotein
From data. accumulated a t Nagasaki and Hiroshima it has been estimated that five million pints of blood would be required in three weeks to treat the casualties resulting from ten atomic bombs dropped simultaneously on as many cities in this country. This is approximately one-half the amount collected hy the Red Cross in this country during the entire war.
1300.000
Fibrinogen 400.000
Edeshn ?AO.OCO
Zein 5~000
Gelotin(undegraded)
lO.WO
riguleI.
stored up to 21 days. Laboratory tests classify blood into groups according to blood types and Rh factors. No two bloods are exactly alike, however, and reactions sometimes occur due to small differences between the blood of the donor and that of a recipient. Reactions may also be caused by typing errors or by contaminated blood. If the patient does not require the oxygen-carrying capacity of Mood, a plasma transfusion may be preferable to a blood transfusion. Liquid plasma may be stored for two years. Irradiation bf the plasma by ultraviolet light appears to have reduced the incidence of homologousserum jaundice caused by plasma injections. Lyopbilized or freeze-dried plasma may be stored for 5 years, but the dry plasma and distilled water to re. . constitute it before use require twice as much shipping and storage space as liquid plasma. All plasma transfusions are expensive and the supply of plasma is limited. In view of the possibilities of atomic warfaye, Dr. DeGowin, an authority on blood and blood transfnsions, has said?
M O ~ . O shapa ~ I ~ ~and sire01 veious proteini
Blood is collected for traisfusioo purposes by drawing it into ra sterile bottle containine an anticoamlant soPresented before the Southern California Section of the Pacific Southwest Association of Chemistry Teachers on May 23, 1952. s t Pasadena City College, Pasadena, California. ONCLEY,J. L., "Symposium on Nutrition," Charles C. Thomas, Springfield, Illinois, 1950, Vol. 11, p. 3.
.4s you can see, we are in serious need of some substitute for blood or plasma. A true blood substitute, that is, an oxygen-carrying material, is probably many years in the future. The so-called plasma substitutes do not have all of the properties of plasma, and for this reason they are frequently referred to as plasma volume expanders or plasma expanders. An effective plasma expander should resemble albumin (Figure l), the material in plasma respousible for most of its osmotic effect. The ideal plasma substitute should be: plasma. 2, Stable during storage at all temperatures. 3, Fluid in climates, a
DEGOWIN, E.L., Surgwy, 28, 121 (July, 1950).
JULY, 1953 Sterile. 5. Nonpywenic (that is, free of fever-produciw contaminants of bacterial origin). 6, (that is, free antibody-forming shncea). 7. constant and uniform in composition. 8. Free of immediate or delayed reactions or damage to the recipient. 9. Completely excreted from the body, after it has served its purpose. 10. Free of interference with blood typing or blood administration. 11. Easily manufactured from plentiful and inexpensive raw material. 4.
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large molecular weight material remains in the body while the small molecular weight material is rapid]y excreted, control of molecular size is important. PVP has been ap~roved for stock~iline. -. .
-
LJo r I
Many materials have been used as plasma substitutes or expanders. One of the first of these was a 2 per cent solution of gum acacia. This solution, widely-used in F ~ ~ U . I. . ~ ~ ~ y r i ~ ~ ~ 1937 and 1938, fell into disuse when it was found to be Gelatin, a protein material obtained from bone or stored in the various vital organs of the body. In reskin, was one of the first colloidal materials used as a cent years many other materials have been used. plasma expander. It is a unique protein which does Pectin, a methoxylated galacturonic anhydride occurnot cause antigenic or foreign protein reactions when ring widely in plant tissues (Figure 2), is effectiveas a . . injected in humans. Various molecular weight. gelatins have been used as plasma expanders. one of these preparations now on the market hears the seal of acceptance of the American Medical Association. This solution is prepared from a high molecular weight (undegraded) gelatin and is a gel a t room temperature. Before use, it must be liquified by warming. Solutions of low molecular weight gelatin (degraded by heat) are liquid at room temperature, hut are rapidly excreted Figvre 2. Pectin by the patient and act as plasma ex~audersfor onlv plasma expander. However, the solution is not stable a~shorttime. During World War 11, a research group under Proa t a pH above 4.2 and must be mixed with a buffer solution before use. Crystallized bovine albumin, fessors Linus Pauling and Dan H. Campbell, at the polyglucose, animal plasma, and a n okra extract also California Institute of Technology, succeeded in modifying so that a 5 per cent solution wasliouid have been used. . - gelatin Recent work on plasma expanders has been concen- at room ternperat~re.~ I n this process, gelatin is reacted with glyoxal, which trated on dextran, polyvinylpyrrolidone, and gelatin solutions. Dextran is a carbohydrate material (Figure couples the gelatin molecules together to form a poly3) formed by the action of a bacterium, Leuconostoc mesateroides, on sucrose.
Dextran has been approved by the National Research Council for use as a plasma expander. However, important problems remain in the control of molecular size, the tests necessary to produce a suitable product, and the reactions which occur in some patients. Polyvinylpyrrolidone (PVP or Periston), a synthetic material (Figure 4) prepared from acetylene, formaldehyde, and ammonia, was developed during World War 11 as the result of extensive screening tests the Germans for an effective plasma expander. Since the
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JOURNAL OF CHEMICAL EDUCATION
370
gelatin (PG of Figure 5).5 The polygelatin is then oxidized and degraded with hydrogen peroxide to form a material which they named "oxypolygelatin." Property
Gelatin
Osmotic pressure (em. of water) at 37°C. 335405 Visemiti relative to water 5-7 a t 37'C. Above 77' Gel mint (OF.)
Ozypolygelatin
350-400 2.1-2.2 Below 50"
Modification of gelatin in this manner lowers the viscosity and gel poi& of the solution as shown in the ta6 CAMPBELL. D. H., J. P. KOEPFLI,AND I,. PAULING,U. S. Patent No. 2,591,133
ble. The osmotic pressure, on the other hand is not significantly changed. Extensive tests in mice, rabbits, dogs, and patients indicate that oxypolygelatin is effective and nontoxic. Elimination of the material from the body, as indicated by urinary excretion, follows much the same pattern as a gelatin solution. Much work has been done by both chemists and clinicians in developing these various plasma expanders for insurance against the possible disaster of atomic warfare. More harm than good can be done, however, if we fail to keep in mind that these substances are in no way replacements for whole blood.
