Introduction to Synthetic Blood

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Contents

1. Understanding Hemoglobin
2. The Ideal Blood Substitute

  • Please click on images to be linked to their references. All images are referenced.

Understanding Hemoglobin

The structure of Hb was determined in 1959 by Max Perutz for which he was awarded a Nobel Prize. Human Hb is a 64 kDa Hemoglobin picturetetrameric protein comprised of two a subunits and two ß-globin subunits that fold into compact quaternary structure (a2ß2). Each a and ß subunit contain an iron-heme group that binds to oxygen molecule allowing for transport. A fully saturated Hb molecule carries a maximum of four oxygen molecules. Environmental conditions such as pO2 , pH, temperature, and pCO2 cause Hb to undergo conformational change from a high oxygen affinity state to a lower oxygen affinity state. Such a transition is also facilitated by the binding of an allosteric effector, 2,3-diphosphoglycerate (DPG), causing a decrease in Hb oxygen affinity and facilitating oxygen offloading. As oxygen is being unloaded CO2 binds to the globin chain, resulting in carbamino-Hb which is then transported to the lungs. However, only about 20% of the CO2 is transported in the blood. The rest of the CO2 is transported in the form of bicarbonates. Local conditions in the lungs including higher pO2 , higher pH, and lower temperature, cause Hb to shift back to the higher oxygen affinity state and dissociate with DPG. Such a transition favors CO2 release, which is then exhaled.

Although blood transfusion is effective, it is not without risks. Allogeneic blood transfusion may cause fatal hemolytic reactions, transmit blood-borne infectious agents, and compromise overall immune function. It is therefore highly desirable to have an artificial oxygen carrying fluid that is readily available, free of infectious agents, and can be used independent of the recipient blood type.

What would constitute the ideal blood substitute?

Blood substitutes or synthetic blood are currently labeled as "oxygen carriers". This is because they are unable to mimic many of the other functions of blood; they do not contain cells, antibodies, or coagulation factors. Their main function is to replacing lost blood volume and oxygen carrying capacity.

The ideal blood substitute could be defined by the following terms:

  • increased availability that would rival that of donated blood, even surpass it
  • oxygen carrying capacity, equalling or surpassing that of biological blood
  • volume expansion
  • universal compatibility: elimination of crossmatching
  • pathogen free: elimination of blood contained infections
  • minimal side effects
  • survivability over a wider range of storage temperatures
  • long shelf life
  • cost efficient

Partial blood substitutes not involved in oxygenation are platelet substitutes. They cover a different realm than oxygen carriers, and are created for mainly one purpose: coagulation. They are considered mainly in the hopes of eliminating risks of bacterial contamination and the short shelf life. Platelets are covered in detail on a later a page.

 

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Webpage designed in April 2005 by students of

Brown University

(Organ Replacement 108, Prof. Lysaght)

Evan Werlin, Garland McQuinn, Gabriel Lepine, Ruth Ophardt