title: Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model.
abstract: OBJECTIVE
  To investigate the effect of sildenafil citrate (SC) on skeletal muscle ischemia-reperfusion (IR) injury in rats.
  
  
  METHODS
  Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG), sildenafil citrate-treated (SCG), and sham group (SG). CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion. Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells). Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups.
  
  
  RESULTS
  Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18 ± 0.1 for the total cohort; 0.14 ± 0.06 for the 4h reperfusion groups and 0.19 ± 0.08 for the 24h groups (p<0.05). The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05).
  
  
  CONCLUSIONS
  Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model.
authors.affiliation: Department of Surgery, Sao Francisco Valley Federal University, Petrolina, PE, Brazil. darmst13@jhmi.edu
authors.forename: Dinani Matoso Fialho de Oliveira
authors.initials: DM
authors.lastname: Armstrong
authors.forename: Anderson da Costa
authors.initials: Ada C
authors.lastname: Armstrong
authors.forename: Regina Célia Bressan Queiroz
authors.initials: RC
authors.lastname: Figueiredo
authors.forename: Joao Eduardo
authors.initials: JE
authors.lastname: Florentino
authors.forename: Paulo Fernandes
authors.initials: PF
authors.lastname: Saad
authors.forename: Karen
authors.initials: K
authors.lastname: Fox-Talbot
authors.forename: Marc Kenneth
authors.initials: MK
authors.lastname: Halushka
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.forename: Murched Omar
authors.initials: MO
authors.lastname: Taha
authors.forename: Djalma José
authors.initials: DJ
authors.lastname: Fagundes
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000032:analysis; D004195:Disease Models, Animal; D005121:Extremities / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D020011:Protective Agents; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D053148:Caspase 3