Researchers at the Medical College of Georgia have found that 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.

“ Hemoglobin S plus nitric oxide behaves much like normal adult hemoglobin, which does not sickle,” says C. Alvin Head, at the Medical College of Georgia.

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,” 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, 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.

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, 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.

“ We knew that nitric oxide would bind to hemoglobin very, very rapidly,” says Head. “ That has been very well proven in the medical literature. In fact, that is the basis of why when you inhale it in very low concentrations, you do not get systemic vascular effects,” he says of the powerful dilator of blood vessels. “ It rapidly crosses the lungs, binds to the hemoglobin, then circulates in the blood.” It was when he was giving nitric oxide to lung transplant patients years ago, patients who might end up breathing the gas for days or weeks at a time without apparent ill effects, that he first considered how it also might benefit sickle cell patients.

Source: Medical College of Georgia, 2005


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