title: Effect of nitric-oxide-generating system on microcirculatory blood flow in skin of patients with severe Raynaud's syndrome: a randomised trial.
abstract: BACKGROUND
  Patients with Raynaud's syndrome have abnormal digital vasoconstriction, which may be secondary to impaired synthesis of, or impaired sensitivity to, nitric oxide. We studied the effect on microcirculation of a nitric-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 study of the microcirculatory response to topical application of a nitric-oxidegenerating gel in 20 patients with severe Raynaud's syndrome, and ten healthy volunteers. We prepared the nitric-oxide-generating system by mixing a solution of KY jelly and sodium nitrite (5% weight/volume), with a solution of KY jelly and ascorbic acid (5% weight/volume). About 0.5 mL of each solution was separately applied to the skin of the forearm (3 cm2), and then mixed with a sterile cotton bud. A similar procedure was done simultaneously 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 doppler fluxmetry, respectively.
  
  
  RESULTS
  In the forearm, blood flow increased significantly after application of the active gel both in patients with Raynaud's syndrome (microcirculatory volume from mean area under the curve 98 [SE 14] to 1024 [130]; microcirculatory flux from 5060 [462] to 74,800 [3940]) and in healthy controls (volume from 85 [19] to 1020 [60]; flux from 4420 [435] to 84,500 [7000]). In the fingers, although baseline blood flow was lower in patients than in controls, 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 33,400 [4200] to 108,000 [13,600] and 52,000 [8950] to 185,000 [19,500]). Increases in blood flow with placebo gel were not significant. No adverse effects were reported.
  
  
  CONCLUSIONS
  In primary Raynaud's syndrome, topical application of a nitric-oxide-generating system can stimulate an increase in both microcirculatory volume and flux.
authors.affiliation: Clinical Microvascular Unit, St Bartholomew's Hospital, London, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Tucker
authors.forename: R M
authors.initials: RM
authors.lastname: Pearson
authors.forename: E D
authors.initials: ED
authors.lastname: Cooke
authors.forename: N
authors.initials: N
authors.lastname: Benjamin
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005385:Fingers / Q000098:blood supply; D005542:Forearm / Q000098:blood supply; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D017156:Photoplethysmography; D011928:Raynaud Disease / Q000188:drug therapy* / Q000503:physiopathology; D016037:Single-Blind Method; D012867:Skin / Q000098:blood supply*; D012977:Sodium Nitrite / Q000008:administration & dosage*
chemical_list: D009569:Nitric Oxide; D012977:Sodium Nitrite; D001205:Ascorbic Acid