News:Duke Research Teams Provide Insight into Small Vessels, Stored Blood, and Nitric Oxide

October 10, 2007 By Grendel Burrell [mailto:grendel.burrell@gmail.com]

Dr. Jonathan Stamler, Duke University, author of one of the publications was quoted in the Miami Herald as stating, "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.” Furthermore, he stated in the Miami Herald article, "The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine.” Stamler and coauthor, James Reynolds, Ph.D., found that, in the lab and in dogs’ blood, the addition of nitric oxide restores the cells' ability to dilate blood vessels and oxygenate tissue. If nitric oxide was restored at any point, the red blood cells were again able to open blood vessels and deliver oxygen to tissues. Researchers had not previously measured the amount of that chemical in stored blood. These findings may provide the opportunity to investigate interventions that would improve the efficacy of transfusions.

Chris Granger, CCU director at Duke University told WikiDoc, “I am increasingly concerned about the potential negative impact of bleeding and of giving blood transfusions, which may be a double edged sword in cardiovascular patients. This is important research that may help to optimize the benefits and reduce the risks of blood transfusions.”

Suspecting that a deficiency in nitric oxide was responsible for increased rates of death and ischemia among transfusion recipients, Dr. Stamler and colleagues, focused their investigation on S-nitrohemoglobin, a derivative of hemoglobin that carries nitric oxide. They found that levels of S-nitrohemoglobin declined rapidly in stored red blood cells, with a 70% drop in the first day (P<0.05). By day 21, they were unable to detect S-nitrohemoglobin in stored blood. Treatment of RBCs with a solution of aqueous nitric oxide increased the level of S-nitrohemoglobin 10-fold when compared with untreated samples. Furthermore, the levels of S-nitrohemoglobin were found to be not significantly different from fresh blood.

Timothy McMahon, MD, PhD, directed another group of researchers at Duke who studied the changes in stored blood over time. Currently blood can only be kept in blood banks for up to 42 days. After that it must be discarded. The authors saw indications of nitric oxide depletion within the first three hours of storing blood. Dr. McMahon’s group tested stored human blood cells for a range of parameters, and they, observed declines in S-nitrohemoglobin and related molecules that were significant (P<0.01) as soon as three hours after the blood was stored.

McMahon et al concluded that one approach would be to test whether replenishing S-nitrohemoglobin or preventing its loss would improve patient outcomes in the setting of a clinical trial. Dr. Robert Harrington, Director of the Duke Clinical Research Institute, told WikiDoc, "These are interesting and potentially important observations. Now we need to test the hypothesis in a randomized, controlled, clinical trial."

Stamler and colleagues’ research was supported by the NIH and the Duke University Anesthesiology Fund. Dr. Stamler and co-author James Reynolds, Ph.D., have consulting and/or equity relationships with Nitrox/N30, a company developing approaches for the treatment of disorders of oxygen delivery.

The American Heart Association and Nitrox/N30 supported the study by Dr. McMahon and colleagues. Dr. McMahon and several co-authors disclosed financial relationships with Nitrox/N30, and two of the study's co-authors are employees of the company. Dr. McMahon is co-inventor of a patent: "Red blood cells loaded with S-nitrosothiols and uses therefore."

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