Work on promising inorganic blood substitute to move forward with $1.5 million grant from NIH

04/15/04

Compound produces circulating “microbubbles” that pick up and deliver oxygen

BUFFALO, N.Y. -- A patient who is losing large amounts of blood presents a medical emergency, requiring proper blood-typing and immediate access to multiple units of compatible blood.

Health workers must hope that transfusing large amounts of blood doesn't add to the emergency and that the patient has no objection to receiving blood products. Then there are the cost and logistics of maintaining large stocks of blood at the ready.

The solution to these problems may lie in an inorganic compound with the cumbersome name dodecaflouropentane emulsion, or DDFPe, a fluorocarbon-based compound used originally as a contrast medium for taking ultrasound images that University at Buffalo researchers are developing as a blood substitute.

Claes Lundgren, M.D., Ph.D., professor in the Department of Physiology and Biophysics in the UB School of Medicine and Biomedical Sciences, is principal researcher on a new $1.5 million, four-year grant from the National Institutes of Health to fund work to define further the compound's use for this purpose.

Lundgren holds up a vial containing the milky emulsion that is half the size of a roll of breath mints. "These five milliliters would be adequate to save the life of a child weighing 10-15 kilograms [26-40 pounds] who had lost half his/her blood supply," he said.

Hugh Van Liew, Ph.D., UB professor emeritus of physiology, and Mark Burkard, Ph.D., who worked with Van Liew as his research assistant, did the initial work to establish DDFPe's use as an oxygen transporter. Lundgren, Van Liew, Burkard and Ingvald Tyssebotn, M.D., Ph.D., UB professor of physiology and biophysics, hold the patent on the product's use as a blood substitute.

The key to this product's ability to prevent hemorrhagic shock lies in the capacity of the emulsion's invisible droplets to expand at body temperature into microbubbles small enough to pass through capillaries, and the strong affinity of the microbubbles for oxygen. If sufficient circulation remains to carry the bubbles to the lungs, they can pick up oxygen and deliver it to tissues.

Nearly all other blood substitutes currently in use or in development are based on hemoglobin, the iron molecule that carries oxygen. Hemoglobin products are expensive and can cause hypertension, Lundgren said. Moreover, they raise some of the same concerns associated with any blood product, and can't be used in persons who refuse transfusion for religious or other reasons.

DDFPe circumvents all the hazards associated with the use of blood products and is 500 times more effective than other fluorocarbon-based blood substitutes, Lundgren said. "We know that if it is administered soon after blood loss, the product has a dramatic effect. Very small amounts introduced into the circulation of a pig after severe blood loss can save the animal from hemorrhagic shock."

His current research will concentrate on finding out how soon the treatment must occur after bleeding begins. The goal is to postpone collapse of the circulatory system during severe blood loss for at least four hours. Researchers will gather physiological and biochemical data relating to the effects of severe blood loss on organs and tissues throughout the investigation.

"Our findings should help to lay a solid foundation for pursuing FDA approval for human use of this blood substitute," Lundgren said. "In the best of circumstances, it would be carried in every ambulance."

Source: Eurekalert & others

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