8/12/2019 Low Oxygen, Nitirc Oxide Worsen Sickle Cell Trait_Medical College of Georgia

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3/20/2014 Low levels of oxgen, nitric oxide worsen sickle cell disease

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IMAGE: This is a photo of Dr.Tohru Ikuta, a molecularhematologist at the MedicalCollege of Georgia at GeorgiaReg ents Un iversity.

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20-Mar-2014

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Contact: Toni Bakertbaker@gru.edu706-721-4421Medical College o f Georgia a t Georgia Regents University

Low levels of oxgen, nitric oxide worsen sickle celldiseaseLow levels of both oxygen and the pow erful blood vesse ldilator nitric oxide a ppear to have an unfortunate s ynergyfor patients with sickle cell disea se , rese archers report.

Their studies indicate that the two conditions common insickle cell disease, d ramatically increas e red blood cells'adhesion to the lining of blood vesse ls walls and thedeb ilitating pain crises that can res ult.

The good new s is that res toring normal levels of nitricoxide can substa ntially reduce red blood cell adhesion,

said Dr. Tohru Ikuta, a molecular hematologist at theMedical College of Georgia at Geo rgia Regents University.Ikuta and Dr. C. Alvin Head , former Chairman of MCG'sDepartment o f Anes thesiology and Periope rative Medicine,are co-correspo nding authors of the s tudy in the journalBlood .

The study also points to a pote ntially new the rapeutictarget, the se lf-adhesion molecule P-selectin, which therese archers found played a central role in increase d red blood cell adhe sion. Low levels of oxygen and nitric oxide both increase express ion of P-selectin.

Hypoxia, or low oxygen levels, can strike a nyone in the face of, for instance, the flu, a ba dcold, strenuous exercise or exposure to high altitud es . Additiona lly, sickle cell patients can

have chronic problems w ith oxygen de livery.

Oxygen is carried in hemoglobin, which travels the bloods tream to its target tissue insidetypically flexible, oval-shaped red blood cells. The si ckled shape o f the hemog lobin in sicklecell disease can impede the journey and often resu lts in oddly shaped , fragile red blood cellsas w ell, said Ikuta. These red blood cells can sp ill their contents into the bloodstream, whereoxygen rea dily binds with the nitric oxide and patients quickly find themselves w ith insufficientlevels of both.

To understand the relationship be twe en low levels of oxygen and nitric oxide, researchersinfu sed sickled red blood cells into mice incapabl e o f producing nitric oxide . The ce llsim mediate ly beg an s ticking to blood ves sel w alls, while no rmal mice w ere unaffected. In theface of low oxygen levels, or hypoxia, cell adhesion increase d s ignificantly in the nitric oxide-deficient mice.

"It's a synergy," Ikuta said. "This sho ws that hypoxia and low nitric oxide levels w orktoge ther in a bad wa y for sickle cell patients."

Whe n they res tored normal nitric oxide levels by having mice b reathe in the short-lived ga s as p atients have done in clinical trials cell adhesion d id not increase whe n oxygen levelsdecreased. Interes tingly, there wa s no additional bene fit from increasing nitric oxide levelsbeyond normal. Rather, resto ring normal nitric oxide levels appe ars the most efficient,effective way to reduce red blood cell adhes ion, the rese archers write.

Clinical trials of nitric oxide therapy to ease pain in sickle cell patients have yielded conflictingresults, with some patients reporting increas ed pa in. The new findings and the fact thatpatients with s ickle cell disea se have s ignificant variability in their nitric oxide levels e venduring a pain crisis likely explains w hy, Ikuta sa id.

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8/12/2019 Low Oxygen, Nitirc Oxide Worsen Sickle Cell Trait_Medical College of Georgia

2/2

3/20/2014 Low levels of oxgen, nitric oxide worsen sickle cell disease

http://www.eurekalert.org/pub_releases/2014-03/mcog-llo032014.php 2/2

Nitric oxide therapy likely would benefit only patients with intermittent or chronically lowlevels, he said. "The answ er is that some patients may not nee d this. And, our studiesindicate tha t there is no therape utic bene fit to increasing levels beyond physiologic levels."

Nitric oxide blood levels can be readily measured, he noted , and are more likely to drop inevery patient during a pain crisis.

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The studies w ere funded in part by the National Institutes of Health.

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