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Published on: November 5, 2019
Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity
M T Gladwin1, A N Schechter, J H Shelhamer
1Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA. mgladwin@nih.gov
Inhaled nitric oxide (NO) did not alter red blood cell oxygen affinity in sickle cell disease patients. However, it increased nitrosylated hemoglobin, suggesting potential for improved microvascular perfusion.
Area of Science:
- Physiology
- Hematology
- Medical Biochemistry
Background:
- Nitric oxide (NO) inhalation may affect sickle cell erythrocytes by altering hemoglobin's oxygen affinity.
- S-nitrosation of beta-chain cysteine 93 is a proposed mechanism potentially impacting sickle cell disease pathophysiology.
Purpose of the Study:
- To investigate the effects of inhaled nitric oxide on oxygen affinity and nitrosylated hemoglobin in sickle cell disease.
- To evaluate the potential of inhaled NO to improve microvascular perfusion in sickle cell disease.
Main Methods:
- Controlled study involving 2-hour treatment with varying concentrations of inhaled nitric oxide.
- Measurement of oxygen affinity (P50) and arterial/venous levels of nitrosylated hemoglobin in controls and sickle cell disease patients.
Main Results:
- Inhaled nitric oxide did not significantly change oxygen affinity (P50) in either controls or sickle cell disease individuals.
- A dose-dependent increase in nitrosylated hemoglobin was observed with NO inhalation, with a significant arterial-venous difference at the highest dose.
- The levels of nitrosylated hemoglobin were insufficient to impact overall hemoglobin oxygen affinity.
Conclusions:
- Inhaled nitric oxide does not alter hemoglobin oxygen affinity in sickle cell disease.
- Augmented nitric oxide transport to the microvasculature via inhalation shows promise for enhancing microvascular perfusion in sickle cell disease.
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