Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension

The primary hypothesis of this study is that glutamine supplementation will improve the
erythrocyte glutamine/glutamate ratio, a biomarker of oxidative stress, hemolysis and
pulmonary hypertension (PH) in sickle cell disease (SCD) and thalassemia (Thal) patients
with PH. PH is defined as a tricuspid regurgitant jet velocity (TRV) on Doppler
echocardiography > 2.5 m/s. We also predict that glutamine therapy will increase arginine
bioavailability and subsequently alter sickle red cell endothelial interaction that can be
identified using endo-PAT technology through nitric oxide (NO) generation, leading to
changes in biological markers, and clinical outcome. Specifically our second hypothesis is
that oral glutamine will decrease biomarkers of hemolysis and adhesion molecules, and
improve the imbalanced arginine-to-ornithine ratio that occurs in hemolytic anemias, leading
to improved arginine bioavailability and clinical endpoints of endothelial dysfunction and
PH in patients with SCD and Thal.