Microcirculatory basis for the design of artificial blood

Artificial blood or blood substitutes are being developed using molecular s olutions of modified free hemoglobin. When these products are used and the red blood cell mass is reduced below the transfusion trigger, there is a co ndition of extreme hemodilution which is characterized by a significant red uction of blood viscosity and NO production, reflex vasoconstriction, decre ased functional capillary density, and impaired microvascular function. Thi s combination of events may be lethal because decreased NO availability may also increase the intrinsic oxygen consumption of the tissue. Current deve lopments in the understanding of the physiology of the microcirculation in extreme hemodilution, and the physical events associated with the substitut ion of red blood cells with molecular hemoglobin solutions show that a viab le "artificial blood"; can be obtained from a new formulation of the produc t, where viscosity is such that when introduced in the circulation the resu lting viscosity of blood is close to normal, the dissociation curve is left shifted and the concentration of hemoglobin is in the range of 3-5 g Hb/dl . This formulation redistributes viscous losses in the circulation causing higher capillary pressure which maintains functional capillary density, a k ey parameter in tissue survival. Furthermore the increased plasma viscosity increases shear stress in the microcirculation, enhancing the production s hear dependent vasodilators, thus counteracting the vasoconstrictor effects due to NO scavenging by free hemoglobin solutions. A principal feature of this formulation is that it maintains microvascular function when the trans fusion trigger is passed and the circulation is subjected to extreme hemodi lution.