Pharmacological mechanisms in the cardiovascular effects of DCLHb, a hemoglobin based blood substitute

textabstractThe search for a clinically useful blood substitute has been stimulated by the inherent limitations of the homologous blood transfusion system, particularly its sufficiency, safety and costs. Blood has been described as the "most complicated fluid in animals" (Winslow, 1992). An attempt to forulUlate a blood substitute is misguided because blood is composed of a complex mixture of fluids, cells, salts, proteins and numerous other molecules having various functions and characteristics. The hemorrhage or loss of blood foremost results in a hypovolemic state and ultimately leads to depletion of oxygen delivering capability (Dracker, 1995). Biologically significant hemorrhage may be defined as a blood loss sufficient to impair oxygen transport (Shoemaker et al., 1973; Bassin et al., 1971; Hauser and Shoemaker, 1982). The major physiological effect of hemorrhage is anemia and hypovolemia leading to drastic aIterations in blood flow to the vital organ systems (Prough et al., 1991). The persistent hypoperfusion to organ systems is responsible for ultimate organ failure even after reperfusion (Knaus et al., 1985). The infusion of large volume of Ringer's lactate in the resuscitation of hemorrhaged patients is associated with several disadvantages. In addition, problems associated with blood transfusion necessitate the development of an alternative resuscitative solution which can be administered in small volumes and is effective in combating the comprom.ised hemodynamics. Haemoglobin-based blood substitutes (oxygen carriers) have been proposed to be effective in the treatment of hemorrhagic shock. The major categories of blood substitutes include the (I) perfluorocarbon solutions and (2) haemoglobin based compounds