Perfluorocarbons
Perfluorocarbons (PFC's) are molecules comprised of carbon and flourine atoms, though they may contain other atoms such as oxygen, nitrogen, and even bromine. They are chemically inert and resistant to thermal and radiation damage.1They have been considered in the use for manufacture of a blood substitute because they act as solvents for all common gases. Approximately 45 mL of oxygen will dissolve in 100mL of a perfluorocarbon liquid. Carbon Dioxide is approximately 2.5 times more soluble than is oxygen.1
Perfluorocarbons are insoluble in other liquids and must be emulsified usually in phospholipids, for use in a blood substitute. The emulsifier is referred to as a surfactant. This emulsion is filtered producing what is usually a sterile product.1 By themselves, PFC's would not make a good blood substitue. PFC's have little or no osmotic or oncotic pressure. It is necessary to add electrolytes and volume expanders to fulfill this requirement.1
Composition of PFC Preparation1
Component PFC surfactant hydroxyethyl
starch
NaCl, KCl, MgCl2, CaCl2, NaH2PO4 NaHCO3 H2O
Role Gas Transport Emulsifier Oncotic Agent Osmotic Pressure and Salts Buffer Continuous Phase
Concentration 25% (w/v) 1-3% (w/v) 3% (w/v) Adjust to 290 mOsm/mL 40mM to volume
Perhaps the most promising type of perfluorocarbon is Fluosol DA. Fluosol DA, manufactured by Green Cross is a mixture of seven parts perfluorodecalin ( a perfluorocarbon), 3 parts perfluorotripropylamine (another perfluorocarbon), 2.7% pluronic F-68 (an emulsifier), and .4% phospholipids from egg yolk to form the membrane coating for the emulsion.13 The average partical size is .118 micrometers.13 One of the reasons Fluosol is considered to be a better choice for a blood substitute than other perfluorocarbons is because it has a shorter tissue retention time. Most perfluorocarbons have tissue retention times T1/2 of 800 days. Fluosol DA has a T1/2 of only 64.7 days. This shorter retention time makes Fluosol a much more desirable alternative.13 It is often referred to as "white blood" because it is not hemoglobin based and doesn't bind iron like normal blood, therefore it lacks the reddish hue of human blood and takes on a color resembling that of milk.11 The advantages of having a totally artificial blood supply like Fluosol DA for emergencies are that it does not need to be cross-matched or screened for diseases, and it has a much longer shelf life than the 35 days of refrigerated human blood. Another advantage Fluosol DA has over human blood is that it can dissolve about three times as much oxygen as human blood, making it much more efficient than normal blood and meaning less Fluosol DA than blood would be needed to perform the same job in the emergency room.11 In fact, the maximum amount of Fluosol used is 20%. This is because of its high viscosity at high concentrations. Since this concentration is so low, and because oxygen can only be dissolved in the perfluorocarbon itself, the patient must breathe air that is between 70 to 90 percent oxygen.13 Fluosol DA also transports carbon dioxide to the lungs for excretion. Fluosol DA must be stored in the frozen state.13 Although the first set of trials of Fluosol DA were lethal to the rats it was tested on (it caused embolism),11 a second series of tests resolved this problem, and a final version of Fluosol DA was developed in 1978.9 Skepticism about the safety of the product has remained high, and after many tests by the FDA, it has only recently been licensed to aid in oxygen delivery during coronary artery balloon angioplasty.10 However, the market for blood substitutes for angioplasty is rather small(about 3% of the total market), making it difficult for companies to turn a profit. The two companies leading the way in regards to perfluorocarbon research are HemaGen in St. Louis, Missouri, and Alliance Pharmaceutical Corporation, which is based in San Diego, California. Of the two Alliance is the farthest ahead in terms of testing PFC's in new areas other than angioplasty; as of May 1993 they were already conducting clinical trials on human subjects.12
Perfluorocarbons are not without their flaws. PFC's can only be removed from the body via the lungs. Because of this, there is a great possibility that they may accumulate in other body organs such as the liver and spleen.5 In addition, there is some evidence that the body's immune system will attack the emulsifying agent which may cause headaches and other side effects.5 PFC's have been shown to increase the patients risk of infection, though it is anticipated that this will be eliminated with futher research.13
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