Effect of nitric-oxide-generating system on microcirculatory blood flow inskin of patients with severe Raynaud's syndrome: a randomised trial

Background Patients with Raynaud's syndrome have abnormal digital vasoconst riction, which may be secondary to impaired synthesis of, or impaired sensi tivity to, nitric oxide. We studied the effect on microcirculation of a nit ric-oxide-generating system applied topically to the finger and forearm of healthy volunteers and patients with primary Raynaud's syndrome. Methods We did a single-blind, randomised, placebo-controlled, cross-over s tudy of the microcirculatory response to topical application of a nitric-ox ide-generating gel in 20 patients with severe Raynaud's syndrome, and ten h ealthy volunteers. We prepared the nitric-oxide-generating system by mixing a solution of KY jelly and sodium nitrite (5% weight/volume), with a solut ion of KY jelly and ascorbic acid (5% weight/volume). About 0.5 mt of each solution was separately applied to the skin of the forearm (3 cm(2)), and t hen mixed with a sterile cotton bud. A similar procedure was done simultane ously on the other arm with KY jelly only (placebo). The procedure was then repeated on the finger pulps. Changes in skin microcirculatory volume and flux were measured bilaterally by infrared photoplethysmography and laser d oppler fluxmetry, respectively. Findings In the forearm, blood flow increased significantly after applicati on of the active gel both in patients with Raynaud's syndrome (microcircula tory volume from mean area under the curve 98 [SE 14] to 1024 [130]; microc irculatory flux from 5060 [462] to 74800 [3940]) and in healthy controls (v olume from 85 [19] to 1020 [60]; flux from 4420 [435] to 84500 [7000]). In the fingers, although baseline blood flow was lower in patients than in con trols, both groups showed increases with application of active gel (volume from 1100 [194] to 3280 [672] and 2380 [441] to 6160 [1160], respectively; flux from 33400 [4200] to 108000 [13600] and 52000 [8950] to 185000 [19500] ). Increases in blood flow with placebo gel were not significant. No advers e effects were reported. Interpretation In primary Raynaud's syndrome, topical application of a nitr ic-oxide-generating system can stimulate an increase in both microcirculato ry volume and flux.