Chemicals Allow Blood to Release More Oxygen : New Hope for Stroke and Heart Patients

A new technique to increase the amount of oxygen that blood can deliver to vital organs was described by researchers Thursday at an American Chemical Society meeting here.

The technique--involving the treatment of red blood cells with chemicals--could be especially useful in treating patients undergoing blood transfusions as well as in keeping alive donor organs destined for transplantation.

And in cases of stroke or heart failure, the ability of blood to release more oxygen would minimize tissue damage.

Clinical trials of the technique are scheduled to begin within two weeks, according to Murray Weiner, clinical pharmacologist of the University of Cincinnati College of Medicine.

Oxygen is carried through the blood by a protein called hemoglobin, which is found inside red blood cells. But in times of stress, Weiner said, “it holds on to the oxygen more tightly than is desirable.”

This is particularly true when blood is lost after an accident or when the flow of blood to all or part of the body is blocked by heart attacks, clogged arteries, or strokes, he said. Blood that has been stored in blood banks for more than a day or two also holds on to oxygen too tightly.

The release of oxygen from blood is made possible by DPG, a naturally occurring chemical in red blood cells. Normally DPG causes about half of the oxygen bound to blood to be released.

But when blood is stored in banks, DPG is lost from the red cells and the blood can deliver only a small fraction of its oxygen immediately--when oxygen is needed the most. The body eventually replaces the DPG, but that process takes hours.

Promise of Phytic Acid

DPG concentrations in banked blood cannot be restored artificially because the molecule is too big to pass through the red cell’s membrane. Scientists have thus been searching for molecules that are more effective than DPG in releasing oxygen as well as for new ways to get such chemicals into the cells.

One promising chemical is phytic acid, a sugarlike compound obtained from plants. Phytic acid is very effective at releasing oxygen, but it is even bigger than DPG.

Scientists have tried many different ways to get phytic acid into red cells, such as breaking the cellular membrane, then allowing it to heal. These techniques have often been very difficult to carry out, however, and many red cells are normally lost, often 50% or more of the total.

Now Weiner thinks he has found a better way.

He uses a chemical called DMSO (dimethyl sulfoxide), which is often used to preserve red cells when they are frozen. DMSO enters the cells readily. When the cells are subsequently exposed to water, DMSO causes them to absorb water rapidly and swell up before the DMSO is washed away.

During this swelling, phytic acid can be carried into the cells with the water. When the DMSO is washed away and the cells return to normal size, the phytic acid is trapped inside.

Weiner says this whole process can take place in seconds. The technique can be used to treat banked blood or can be used on a patient’s own blood in a process similar to dialysis.

Phytic acid-treated blood is much more efficient than normal red cells at releasing oxygen, Weiner said. And tests in France with pigs, whose circulatory systems are very similar to those of humans, have shown that the treated blood reduces blood flow so that the heart does less work, even though blood pressure and pulse rate remain constant.

Working with scientists at the Navy Blood Research Center in Boston, Weiner has shown in baboons that the treated blood remains in the circulatory system just as long as normal blood and that no ill effects are associated with its use.

The group has just received approval from the U.S. Food and Drug Administration to begin similar tests in healthy individuals to show that the treated blood is safe.

The first clinical use of the treated blood, Weiner said, will probably be in sickle cell anemia patients when they require blood transfusions during surgery. Typically, when such patients receive blood from a blood bank, the added blood holds on to its oxygen more tightly than their own blood. When this happens, their own blood gives up its oxygen, and the cells deform into a sickle shape, creating many physical problems for the patient.

‘Sickling’ Prevented

Tests in the laboratory, Weiner said, show that treated blood releases its oxygen before the patient’s blood does, and “sickling” is prevented.

Weiner said they chose sickle cell disease to study first because it is “the condition in which it is easiest to demonstrate efficacy.” If those trials prove successful, he added, they will study heart disease and stroke.

Biochemist Reinhold Benesch of Columbia University, who is working on other ways to increase oxygen release, said that Weiner’s work looks very promising, but cautioned that he would like to see more information about the possible side effects of phytic acid before reaching any conclusions.