Missing nitric oxide may be why banked blood is a risk to some patients
Two research groups have discovered that nitric oxide disappears rapidly from banked blood -a finding that may explain recent medical studies showing that blood transfusions can sometimes increase a patient’s chances of dying from a lack of oxygen.
In red blood cells, nitric oxide (NO) is covalently attached to cysteine residues of haemoglobin. This nitrosylation serves as a signal that makes blood vessels dilate and so increases the amountof oxygen reaching cells.
But Jonathan Stamler from the Duke University Medical Center at Durham, North Carolina, who led one of the two teams, says that the signal goes missing from stored red blood cells.
’S-nitrosylated haemoglobin is short-lived in situ, as it reacts with cellular nucleophiles such as glutathione,’ Stamler explains. ’It can be repleted in vivo by NO synthetase, but not ex vivo.’
Stamler’s team found rapid decline of nitroso-haemoglobin and its accompanying vasodilatory effect during storage in most samples they examined. The researchers were able to restore the vasodilatory effect of banked blood samples at any time during the 42-day storage period legally allowed for transfusion by exposing them to NO.1
Separately, the group of Timothy McMahon, also at Duke, also found that the vasodilation triggered by red blood cells is significantly reduced in samples processed and stored according to the guidelines of the American Association of Blood Banks (AABB). Using two distinct methods of analysis, McMahon’s group found that the nitroso-haemoglobin in the samples almost vanished within the first three hours of storage and remained negligibly small during the next 42 days.2
The results of both groups, which have both worked in association with the Duke spinout company Nitrox (now rebranded N30 Pharma), appear to suggest immediate measures that can be implemented both to monitor the quality of banked blood samples, and to regenerate samples that have lost their NO.
’Strategies to correct or prevent these problems should now be tested with the goal of improving patient outcomes with transfusions, which frequently do more harm than good unless they are restricted,’ McMahon said.
et al.,PNASet al.,PNAS, 2007, DOI: 10.10.1073/pnas.0708160104