title: Protective effects of angiotensin II type-1 receptor blockade with olmesartan on spinal cord ischemia-reperfusion injury: an experimental study on rats.
abstract: BACKGROUND
  Spinal cord injury is a major complication of thoracoabdominal aortic operations. We aimed to investigate neuroprotective role of olmesartan administered to rats before ischemia against ischemia-reperfusion (I-R) injury.
  
  
  METHODS
  Twenty-four Wistar albino rats were randomly divided into three groups (n = 8 per group): group I (control group, the sham-operation group), group II (the I-R group undergoing aortic occlusion without pharmacologic treatment), and group III (olmesartan-treated group receiving 3 mg/kg/d olmesartan for 14 days before ischemia). Spinal cord ischemia was induced by infrarenal aortic clamping for 45 minutes, followed by reperfusion. Neurological status was assessed by using modified Tarlov score preoperatively and at 48 hours postoperatively. Spinal cords were harvested for histopathologic examination with hematoxylin-eosin staining and biochemical analysis for tissue malondialdehyde, superoxide dismutase, and glutathione peroxidase levels.
  
  
  RESULTS
  The rats in the ischemia group had severe deficits including paraplegia after surgery, and they had a worse neurological status compared with the sham group (p < 0.05). The mean Tarlov scores in the ischemia and olmesartan-treated groups at 48 hours postoperatively were 1.6 +/- 0.4 and 2.2 +/- 0.9, respectively (p < 0.05). Histopathologic analyses demonstrated typical changes of ischemic necrosis in the ischemia group; however, olmesartan attenuated tissue necrosis. Decreased spinal cord tissue malondialdehyde (p = 0.047) and increased tissue superoxide dismutase (p = 0.001) and glutathione peroxidase (p = 0.009) levels were measured in the olmesartan-treated group compared with the ischemia group.
  
  
  CONCLUSIONS
  Olmesartan may protect the spinal cord from I-R injury and reduce the incidence of associated neurological dysfunction after temporary aortic occlusion.
authors.affiliation: Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Adem
authors.initials: A
authors.lastname: Güler
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Sahin
authors.forename: Alper
authors.initials: A
authors.lastname: Ucak
authors.forename: Burak
authors.initials: B
authors.lastname: Onan
authors.forename: Kaan
authors.initials: K
authors.lastname: Inan
authors.forename: Emin
authors.initials: E
authors.lastname: Oztaş
authors.forename: Siddik
authors.initials: S
authors.lastname: Arslan
authors.forename: Bülent
authors.initials: B
authors.lastname: Uysal
authors.forename: Ufuk
authors.initials: U
authors.lastname: Demirkiliç
authors.forename: Harun
authors.initials: H
authors.lastname: Tatar
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery; D003250:Constriction; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009043:Motor Activity; D009336:Necrosis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000068557:Olmesartan Medoxomil; D010264:Paraplegia / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D018696:Neuroprotective Agents; D013777:Tetrazoles; D008315:Malondialdehyde; D000068557:Olmesartan Medoxomil; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase