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Academic Emergency Medicine Volume 10, Number 5 552,

© 2003 Society for Academic Emergency Medicine

ISCHEMIA/REPERFUSION

L-arginine, the Substrate for Nitric Oxide, Is Significantly Low in Acute Vasoocclusive Sickle Cell Crisis

Bernard L Lopez, Allyson A Kreshak, Claudia R Morris, Samir K Ballas, Linda Davis-Moon and Xin L Ma

Jefferson Medical College: Philadelphia, PA, Children's Hospital Oakland: Oakland, CA

ABSTRACT

Objective: Vasoocclusive crisis (VOC) is the most common presentation of adult sickle cell patients in the ED. Our prior studies demonstrated an inverse relationship between nitric oxide (an endogenous vasodilator) metabolite (NOx) levels and pain scores during VOC, suggesting that an NO deficiency may result in vasoconstriction with resultant ischemia and pain. Our prior study (AEM 2002; 9:409) of 34 subjects revealed low L-arginine (l-arg, the substrate for NO formation) and NO levels in VOC. We report the final data of the largest l-arg study in adult VOC. Methods: Patients > 18 years presenting to the ED with uncomplicated, typical VOC had plasma l-arg and NO levels obtained prior to treatment. L-arg was measured using ion-exchange chromatography and NOx was measured by an NO-specific chemiluminesence technique (SIEVERS 280I NO analyzer). Excluded were those with atypical pain or acute, co-existing illness. Pain was measured prior to and at the end of ED treatment using a 100 mm visual analog scale (VAS). Subjects were divided into a persistent pain group ({Delta}VAS < 13 mm) and an improved pain group ({Delta}VAS >= 13 mm). Results: 50 subjects with VOC had a significantly low plasma l-arg level (29.78 µM ± 11.21, p < 0.05 vs. steady-state control = 41.16 µM ± 5.04) and significantly low plasma NOx (12.33 µM ± 10.28, p < 0.05 vs steady-state control = 25.2 µM ± 2.6). Neither L-arg nor NOx levels could predict the clinical course of VOC—there was no difference in either measurement between the persistent pain and the improved pain groups nor between those admitted and discharged from the ED. Conclusions: L-arg, the substrate for NO, is significantly low in adult VOC patients in the ED. However, this low l-arg level is still ten times higher than the km of the enzyme NO synthase. Serum l-arg levels alone, therefore, cannot explain low NO levels in VOC and suggest that other mechanisms such as altered intracellular transport may play a significant role.

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