Inhaling a small dose of nitric oxide gas may one day help sickle cell patients avoid pain crises and live healthier lives, researchers say.
Nitric oxide may help normalize a sickle cell patient's hemoglobin by restoring the natural charge and shape to the oxygen-carrying component of red blood cells, Medical College of Georgia researchers have found.
"Hemoglobin S plus nitric oxide behaves much like normal adult hemoglobin, which does not sickle," says Dr. C. Alvin Head, chair of the Medical College of Georgia Department of Anesthesiology and Perioperative Medicine.
In fact, their test-tube studies of human hemoglobin show nitric oxide not only prevents unhealthy clustering of hemoglobin S molecules but can melt existing polymers, leaving more hemoglobin free to do its job of oxygen delivery to the body.
Inhaling the short-acting gas naturally found on hemoglobin allows low concentrations to come in close contact with red blood cells and essentially turns the lungs into a hemoglobin repair shop.
"This is clearly a novel idea," Dr. Head says of findings that show the extra nitric oxide changes the neutral charge of hemoglobin S to the slightly negative charge much like normal hemoglobin. It could also help prevent development of the unwanted hemoglobin S polymers in the microcirculation when oxygen levels are lower, once hemoglobin releases its oxygen to the tissues.
Those surface irregularities create unfortunate puzzle pieces that help hemoglobin S molecules fit together to form the polymer. The neutral charge permits this abnormal bonding that eventually deforms the red blood cells that carry them, Dr. Head says. "As the polymer gets longer, it binds to the red cell membrane and begins to deform the cell. If you can prevent this from occurring, you won't get the abnormal-shaped cells," he says or the resulting pain crises as the sickled cells deprive body tissue of adequate oxygen.
Add nitric oxide to the equation and the newly created negative charge helps hemoglobin molecules repel each other and stay independent, round and functional, he says of findings being presented during the American Society of Anesthesiologists' annual meeting in Atlanta Oct. 22-26. Sabina Wang, a research associate who performed these studies, will present their work. Dr. Steffen Meiler, vice chair of research for the MCG Department of Anesthesiology and Perioperative Medicine, also is a contributing co-author.
Oxygen also can break apart dangerous polymers, but the smaller nitric oxide is more agile, has a higher affinity for hemoglobin and – perhaps most importantly – can normalize the charge of hemoglobin S, Ms. Wang notes.
Anesthesiologists and other physicians already give low doses of nitric oxide to patients for reasons such as hypoxic respiratory failure in the newborn.