Abstract
Rationale:
Acute changes in cardiopulmonary hemodynamics that include tricuspid-regurgitant-jet-velocity elevation measured by Doppler-echocardiography are often encountered during sickle cell vaso-occlusive pain and acute chest syndrome. Arginine and nitric oxide depletion develop in patients with these complications. Arginine administration may therefore improve nitric oxide bioavailability and potentiate pulmonary vasodilatation.
Objectives:
To evaluate effects of L-arginine supplementation on Doppler-indices of cardiopulmonary hemodynamics in children with sickle cell anemia experiencing pain.
Methods:
A prospective double-blinded randomized placebo-controlled trial of oral arginine in children with sickle cell anemia age 5-17 years hospitalized with severe pain and/or acute chest syndrome.
Measurements:
Blood biomarkers and Doppler-echocardiographic indices of cardiopulmonary hemodynamics, were measured pre- and post-supplementation. The mean change in tricuspid-regurgitant-jet-velocity, pulmonary artery systolic pressure, mean pulmonary artery pressure and other indices of cardiopulmonary hemodynamics were tested with paired Student's t-test and correlated with markers of arginine bioavailability using Pearson correlation.
Main results:
Sixty-six children were randomized into arginine vs placebo groups. An elevated TRV≥2.5m/s was seen in 40 (61%) patients. A day-5 Doppler-echocardiogram was performed in 47 patients who remained hospitalized. A greater reduction in median tricuspid-regurgitation-jet-velocity occurred in the arginine group compared to placebo (22.2%, n=22 vs. 3.8%, n=25 p<0.01). A larger percent increase in global arginine bioavailability was associated with a lower tricuspid-regurgitation-jet-velocity after 5 days of supplementation, r=-0.533, p=0.001. Significant differences in multiple indices of cardiopulmonary hemodynamics and mean Pro-BNP were also noted after arginine therapy.
Conclusions:
Oral arginine supplementation improves cardiopulmonary hemodynamics during sickle cell disease vasoocclusive pain and acute chest syndrome. Clinical trial registration available at https://pactr.samrc.ac.za/, ID: PACTR201611001864290.
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