title: Pathophysiological aspects and clinical outcome of intra-anal application of isosorbide dinitrate in patients with chronic anal fissure.
abstract: BACKGROUND
  Relaxation of the internal anal sphincter can be achieved by local application of exogenous nitric oxide donors.
  
  
  OBJECTIVE
  To evaluate the influence of topical application of isosorbide dinitrate (ISDN) on anal pressure, anodermal blood flow, and fissure healing.
  
  
  METHODS
  Thirty four consecutive patients (male/female: 18/16; mean age (SEM): 39 (10)) with a chronic anal fissure were studied.
  
  
  METHODS
  All patients were treated for at least six weeks or a maximum period of 12 weeks. Before treatment and at three and six weeks 22 patients underwent conventional anal manometry and laser Doppler flowmetry of the anoderm.
  
  
  RESULTS
  Within 10 days the fissure related pain was resolved in all patients. At six, nine, and 12 weeks the anal fissure was completely healed in 14, 22, and 30 patients respectively. At three and six weeks manometry was performed at least one hour after the last application of ISDN. These recordings showed a reduction of the maximum resting anal pressure (mean (SD), pretreatment 111 (26) mm Hg; three weeks 86 (19); six weeks 96 (27), p < 0.001). Simultaneous recordings of anodermal blood flow showed a significant increase of flow (pretreatment 0.53 (0.17); three weeks 0.80 (0.16); six weeks 0.76 (0.31), p < 0.005). The mean (SEM) duration of follow up after successful outcome was 11 (5) months. Within this period fissure relapsed in two of 30 patients (7%), eight and 10 weeks after treatment had been stopped.
  
  
  CONCLUSIONS
  Local application of ISDN reduces anal pressure and improves anodermal blood flow. This dual effect results in a fissure healing rate of 88% at 12 weeks. This new and simple treatment modality seems to be an attractive alternative for the current available surgical procedures.
authors.affiliation: Department of Surgery, University Hospital Dijkzigt, Rotterdam, Netherlands.
authors.forename: W R
authors.initials: WR
authors.lastname: Schouten
authors.forename: J W
authors.initials: JW
authors.lastname: Briel
authors.forename: M O
authors.initials: MO
authors.lastname: Boerma
authors.forename: J J
authors.initials: JJ
authors.lastname: Auwerda
authors.forename: E B
authors.initials: EB
authors.lastname: Wilms
authors.forename: B H
authors.initials: BH
authors.lastname: Graatsma
mesh_terms: D000328:Adult; D001003:Anal Canal / Q000098:blood supply / Q000503:physiopathology; D002908:Chronic Disease; D005260:Female; D005401:Fissure in Ano / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008365:Manometry; D008875:Middle Aged; D011312:Pressure; D012039:Regional Blood Flow; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate