Increased plasma total nitric oxide among patients with severe chronic venous disease

Skin damage in chronic venous disease (CVD) may be partially attributable to free radical injury including that of nitric oxide (NO). The aim of this study was to measure total plasma NO in patients with CVD compared to control subjects.

Forty-four patients with CVD and 13 control subjects with no arterial or venous disease were included in this study. The patients underwent duplex ultrasonography to confirm the extent of the venous disease and were assigned to the appropriate CEAP clinical stage. Exhaustive exclusion criteria were applied to prevent the influence of dietary intake and other diseases in total NO production. Patients were studied after resting supine for 10 min in room temperature. Blood samples were taken from the long saphenous or a dorsal foot vein. Plasma was separated and frozen at -80 degrees C within 1 hour of venesection. Total NO was assayed with a colorimetric test using the Griess reaction (R&D systems, UK).

The median total NO levels among patients with the C5 was 55 micromol/L (interquartile range 51 to 64); with C4 was 53 micromol/L (interquartile range 44 to 58); C2 and C3 was 44 micromol/L (interquartile range 36 to 50) and with control subjects it was 43 micromol/L (interquartile range 41 to 50). Those with healed ulcers (C5) showed statistically raised NO levels compared to controls (median difference 12 micromol/L [95% confidence interval: 5-22]). Combining the data in the C4 and C5 patients results in a set of data significantly different from control subjects (median difference 9 [95% C.I. 2-15]).

Raised total NO is strongly associated with the more severe stages (lipodermatosclerosis and healed ulceration), in patients with venous disease.