Duke University Medical Center researchers have found that blood begins to lose nitric oxide, a key gas that opens up blood vessels to facilitate the transfer of oxygen from red blood cells to oxygen-starved tissues, as soon as it is stored in blood banks after being donated by a person.
The new findings, reported in two separate papers appearing online in the Proceedings of the National Academy of Sciences, suggest that millions of people may be receiving transfusion with blood that has impaired its ability to deliver oxygen.
The researchers have also found that the ability of red blood cells to transfer oxygen to tissues may be restored by adding nitric oxide back to stored blood before transfusion.
Several previous studies have shown that patients who receive blood transfusions have higher incidences of heart attack, heart failure, stroke, and even death.
"It doesn't matter how much oxygen is being carried by red blood cells, it cannot get to the tissues that need it without nitric oxide," said Dr. Duke's Jonathan Stamler, senior author of one of the PNAS papers, whose group originally discovered the role of red blood cell nitric oxide in oxygen delivery.
"Nitric oxide opens up the tiny blood vessels, allowing red blood cells to pass and deliver oxygen. If the blood vessels cannot open, the red blood cells back up in the vessel and tissues go without oxygen. The result can be a heart attack or even death," he added.
He says that despite knowing that the banked blood is not the same as blood in the body, the researchers have for long been unclear about the reasons behind blood's association with worse outcomes.
"The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine. Most people do not appreciate that blood has the intrinsic capacity to open blood vessels, thereby enabling oxygen to get to tissues. Banked blood cannot do this properly," said Stamler, a professor of cardiovascular and pulmonary medicine.
The researcher, however, admitted that transfusions still held importance.
"Banked blood is truly a national treasure that needs to be protected. Blood can be life saving, only it is not helping the way we had hoped and in many cases it may be making things worse. In principle, we now have a solution to the nitric oxide problem--we can put it back--but it needs to be proven in a clinical trial," Stamler said.
In the US, national blood banks require not to store blood for more than 42 days after donation, and on expiration of this period, the unused blood must be discarded.
Dr. Timothy McMohan, a member of the team of Duke researchers, set out to determine exactly what happens to banked blood over the 42 days period, and sampled the blood at regular intervals.
"We were surprised at how quickly the blood changes - we saw clear indications of nitric oxide depletion within the first three hours. Of concern to us is that nitric oxide levels become depressed soon after collection, suggesting that even 'fresh' blood may have adverse biological characteristics," said McMahon, an associate professor of pulmonary medicine.
As blood is often given to patients to prevent heart attacks, the researchers measured blood flow to the hearts of oxygen-deprived animals.
"When we gave stored blood it couldn't increase blood flow properly," Stamler said.
"However, after replacing the nitric oxide, blood flow to the heart was increased, reflecting increased blood vessel dilation. This suggests that adding nitric oxide to human banked blood could theoretically improve its ability dilate blood vessels and thus prevent heart attacks and even death in patients," he added.
Both McMohan and Stamler insist that blood has both benefits and risks, and stress that it be evaluated in the same manner as medications.
"There is little doubt that transfused blood can be harmful. We are only uncertain about how serious the problem is. The availability of a potential solution will hopefully focus the attention of the medical community on the potential magnitude of this problem," said Stamler.