Artificial Blood: Why and When?
The idea of producing artificial blood may sound simple, at least until you think more about all that we mean when we talk about blood. Ever since William Harvey first described the circulation of blood in 1616, scientists have thought about whether blood that had been intentionally or accidentally lost could be replaced by other fluids. Those early scientists thought that by doing so, diseases could be cured and even that personalities could be changed. Obviously, there were some interesting but disappointing experiments!
Our modern efforts to produce artificial blood were spurred by the military in World Wars I and II and, more recently, by the discovery in the early 1980s that HIV could be transmitted by blood transfusion. If a liquid, or even a partial liquid, containing microparticles that could replace blood were available, completely safe and stable for long periods; it would be extremely useful in emergencies, disaster and wars-as well as in countries where blood is not collected and stored as it is in the U.S. and western Europe. In the U.S., for example, situations not usually associated with a need for artificial blood include patients with stroke (the third leading cause of death in the U.S.), where limited studies have shown that one form of artificial blood reduces long-term effects through the oxygenation of the tissues. Another example is sickle cell disease, which affects 100,000 Americans and as many as 50 million people in Africa (in parts of which HIV infection is endemic and donors are nearly non-existent and storage of blood is a severe problem).
Keep in mind that blood does many things. Currently the artificial blood being tested is designed to do only one of them: carry oxygen and carbon dioxide. No substitutes have been invented that can replace the other vital functions of blood: coagulation and immune defense. Thus, replacement solutions being developed today are more accurately described as oxygen carriers. There are basically two types of oxygen carriers, which differ in the way they transport oxygen. One is based on perfluorochemicals (PFC); the other based on hemoglobin.
The first are inert materials that can dissolve approximately 50 times more oxygen than blood plasma. These perfluorochemicals are inexpensive and fairly easy to produce and can be prepared completely free of biological materials; therefore, there is no risk of infectious agents contaminating them. In order to work, however, they must be combined with other materials that enable them to mix in with the bloodstream. These companion materials are fatty compounds known as lipids. They take the form of an emulsion, a suspension of extremely small particles in a liquid that can be injected into a patient. Improved versions of perfluorocarbon emulsions are being developed and are under various phases of FDA approved investigation. Hemoglobin-based oxygen carriers (HBOCs) utilize the same oxygen-carrying protein molecule found in blood. Oxygen bonds chemically to the hemoglobin, whereas it dissolves only into the PFC emulsions. HBOCs differ from red blood cells in that the hemoglobin is not contained within a membrane. The membrane of a red blood cell contains the antigen molecules that determine the type of the blood (A, B, AB or O). Because HBOCs have no membranes, they do not need to be cross-matched by type and can be given to any patient without previous testing. In addition, these artificial oxygen carriers can be stored for long periods, greatly simplifying the work of the blood bank. Best of all, HBOCs can be used in situations and locations where real blood is not available, as at disaster sites, underdeveloped countries or battle zones.
Two main problems arise when hemoglobin is removed from the red blood cells; these problems account for the large amount of scientific research that has been conducted so far in this area. First, the red cell membrane protects hemoglobin from degradation and protects tissues from the toxic effects of free hemoglobin. Second, when oxygen is being delivered by a cell-free carrier instead of red blood cells, complex biological mechanisms alter the flow through the smallest blood vessels (the arterioles and capillaries). Major advances have been made in overcoming both of these problems, and several HBOC products are now in advanced human trials. It is anticipated that in the next one to two years the first of these products will become available to physicians for use in patients.
While PFC's may never eliminate the practice of blood transfusion or be approved as a blood substitute, they do hold a great deal of potential for other applications. They could be incorporated into solutions used in open heart surgery, and in supplying devascularized organs with oxygen prior to transplantation. Along those same lines, they could be used to perfuse the myocardium or brain tissue in heart attacks and strokes, oxygenating obstructed regions due to blockage and hopefully improving survival and recovery.
Another possible area of application is in cancer therapy. PFC's could increase the oxygenation of tumors, consequently benefiting radiation and/or chemotherapy in cancer treatment. Chemotherapeutic drugs could be added to the PFC and carried along to the site of the cancer. Also, local application of toxic doses of PFC resulted in the necrosis of cancer cells. This is especially promising in the treatment of cancers of the head and neck regions, which are currently difficult to treat.
Other possible applications include the treatment of fungal/bacterial skin and GI tract infections, oxygen deficient conditions (i.e. carbon monoxide poisoning), Alzheimer's disease and medical imaging.