Nitric oxide could make blood transfusions safer

June 25, 2013 by Marcia Malory, Medical Xpress report

Bags of blood collected during donation. Image: Wikipedia.
(Medical Xpress)—Blood transfusions are supposed to save lives. Doctors give transfusions to severely ill or injured people with the expectation that their conditions will improve. In fact, transfusions do not always help and can even make things worse. When red blood cells are stored, their ability to deliver oxygen decreases. This can cause tissue hypoxia in patients who receive blood transfusions, resulting in severe complications. In a study that appears in the Proceedings of the National Academy of Sciences, Jonathan Stamler of Case Western Reserve University in Cleveland and his colleagues show that adding nitric oxide to stored red blood cells improves oxygen delivery.

Red blood cells deliver oxygen to tissues throughout the body. A transfusion increases the amount of red blood cells in the body, which should, presumably, increase , improving tissue health. However, the oxygen-carrying capacity of stored red blood cells decreases over time. Consequently, transfusions of stored blood can cause tissue hypoxia. Eventually, this can lead to heart attack, or death.

Stamler and his team reasoned that a decrease in nitric oxide levels impairs the ability of banked to deliver oxygen after transfusion. When nitric oxide attaches to , it forms S-nitrosohemoglobin (SNO-Hb), which causes blood vessels to dilate, making it easier for oxygen to reach cells. When blood is stored, SNO-Hb levels decrease over time.

The researchers studied the effect of adding nitric oxide to banked blood, a process known as renitrosylation, before using this blood in transfusions performed on mice, rats and sheep.

They performed top-up transfusions on mice using one-day-old and seven-day-old blood. After one day of storage, rodent blood loses more than 70% of its SNO-Hb. Mice that received renitrosylated blood maintained normal in . In comparison, oxygen levels declined in mice given untreated blood.

Stamler and his colleagues then tested the effect of renitrosylation on blood transfusions performed on anemic rats. After removing between 25 and 30 percent of blood volume, the researchers performed transfusions, using either untreated or renitrosylated stored blood. Oxygen levels in the muscle tissues of rats that received untreated blood remained low. However, rats receiving renitrosylated blood experienced increases in tissue oxygen levels.

Studies of anemic sheep revealed similar results. Stamler's team anesthetized sheep two days after bloodletting and transfused them with 14-day-old blood. Treatment with renitrosylated blood improved vasodilation, blood flow to the kidneys and kidney function. Sheep that received transfusions of renitrosylated blood while remaining awake also experienced sustained improvements in oxygen delivery.

The team suggests that restoring levels of nitric oxide in banked blood would improve outcomes in human patients.

Explore further: Discovery opens new options for improving transfusions

More information: S-nitrosylation therapy to improve oxygen delivery of banked blood, PNAS, Published online before print June 24, 2013, doi: 10.1073/pnas.1306489110

From the perspectives of disease transmission and sterility maintenance, the world's blood supplies are generally safe. However, in multiple clinical settings, red blood cell (RBC) transfusions are associated with adverse cardiovascular events and multiorgan injury. Because ∼85 million units of blood are administered worldwide each year, transfusion-related morbidity and mortality is a major public health concern. Blood undergoes multiple biochemical changes during storage, but the relevance of these changes to unfavorable outcomes is unclear. Banked blood shows reduced levels of S-nitrosohemoglobin (SNO-Hb), which in turn impairs the ability of stored RBCs to effect hypoxic vasodilation. We therefore reasoned that transfusion of SNO-Hb–deficient blood may exacerbate, rather than correct, impairments in tissue oxygenation, and that restoration of SNO-Hb levels would improve transfusion efficacy. Notably in mice, administration of banked RBCs decreased skeletal muscle pO2, but infusion of renitrosylated cells maintained tissue oxygenation. In rats, hemorrhage-induced reductions in muscle pO2 were corrected by SNO-Hb–repleted RBCs, but not by control, stored RBCs. In anemic awake sheep, stored renitrosylated, but not control RBCs, produced sustained improvements in O2 delivery; in anesthetized sheep, decrements in hemodynamic status, renal blood flow, and kidney function incurred following transfusion of banked blood were also prevented by renitrosylation. Collectively, our findings lend support to the idea that transfusions may be causally linked to ischemic events and suggest a simple approach to prevention (i.e., SNO-Hb repletion). If these data are replicated in clinical trials, renitrosylation therapy could have significant therapeutic impact on the care of millions of patients.

Press release

Related Stories

Discovery opens new options for improving transfusions

July 15, 2011
Donated red blood cells lose a key feature that diminishes their lifesaving power the longer they have been stored, according to researchers at Duke University Medical Center.

Drug approved for inherited blood disorder

January 24, 2013
(HealthDay)—Exjade (deferasirox) has been approved by the U.S. Food and Drug Administration to remove excess iron in the blood among people with a genetic blood disorder called non-transfusion-dependent thalassemia (NTDT).

Researchers work to improve efficacy of blood transfusions for preterm babies

November 22, 2012
(Medical Xpress)—Results of new research from the University of Adelaide are a promising step forward in helping to improve the quality of life-saving blood transfusions for preterm babies, by reducing the likelihood of ...

'Shelf life' of blood? Shorter than we think

March 4, 2013
A small study from Johns Hopkins adds to the growing body of evidence that red blood cells stored longer than three weeks begin to lose the capacity to deliver oxygen-rich cells where they may be most needed.

Transfusion not always best treatment for anemia, age of stored blood may play a role

October 12, 2011
University of Kentucky researchers, including lead author Samy Selim of the Division of Cardiovascular Medicine and the Saha Cardiovascular Research Center, have recently published a paper suggesting that transfusion may ...

Researchers say it's time to treat anemia seriously

January 24, 2013
Up to one-third of patients undergoing surgery in Ontario have a treatable form of anemia but are not optimally treated for it.

Recommended for you

Researchers explore new way of killing malaria in the liver

December 8, 2018
In the ongoing hunt for more effective weapons against malaria, international researchers said Thursday they are exploring a pathway that has until now been little studied—killing parasites in the liver, before the illness ...

Study may offer doctors a more effective way to treat neuroblastoma

December 7, 2018
A very large team of researchers, mostly from multiple institutions across Germany, has found what might be a better way to treat patients with neuroblastoma, a type of cancer. In their paper published in the journal Science, ...

Progress made in transplanting pig hearts into baboons

December 6, 2018
A large team of researchers from several institutions in Germany, Sweden, Switzerland and the U.S. has transplanted pig hearts into baboons and kept them alive for an extended period of time. In their paper published in the ...

'Chemo brain' caused by malfunction in three types of brain cells, study finds

December 6, 2018
More than half of cancer survivors suffer from cognitive impairment from chemotherapy that lingers for months or years after the cancer is gone. In a new study explaining the cellular mechanisms behind this condition, scientists ...

Hybrid prevalence estimation: Method to improve intervention coverage estimations

December 6, 2018
LSTM's Professor Joseph Valadez is senior author on a new study published today in the Proceedings of the National Academy of Sciences, which outlines proposals for a more accurate estimator of health data.

World's smallest wearable device warns of UV exposure, enables precision phototherapy

December 5, 2018
The world's smallest wearable, battery-free device has been developed by Northwestern Medicine and Northwestern's McCormick School of Engineering scientists to measure exposure to light across multiple wavelengths, from the ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (1) Jun 26, 2013
This makes sense.
NO inhalation therapy has been used for some time to dilate capiliaries and increase blood flow in Blue Baby syndrome and ARDS (Acute Respiratory Distress Syndrome) where the alveolar capillary network collapses and leads to multiple organ failure.
Viagra works on the same principle by inhibiting the enzyme which breaks down NO, thus increasing the level of NO and blood flow.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.