Additive effect of allopurinol and deferoxamine in the prevention of spinal cord injury caused by aortic crossclamping.
Fourteen domestic swine were divided into two groups. Group A (n = 7) was the control group, in which no pharmacologic intervention was applied. In group B (n = 7), the ischemic-reperfused spinal cord was treated with the combination of allopurinol (50 mg/kg/day for 3 days before the day of operation) and deferoxamine (Desferal, 50 mg/kg administered intravenously over 3 to 4 hours). The administration of deferoxamine was completed 1 hour before crossclamping. The crossclamp was placed on the descending aorta just distal to the left subclavian artery for 30 minutes. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. Methods of assessment included an evaluation of the neurologic status of the animals by quantitative Tarlov criteria, blood flow by radiolabeled microspheres, and histologic examination of the spinal cord. All animals in the control group, group A, were completely paraplegic with 0% recovery by Tarlov criteria at 24 hours after the removal of the crossclamp. In contrast, all animals in group B, in which the combination of allopurinol and deferoxamine was used, completely recovered (100% recovery by Tarlov criteria), and at 24 hours after the ischemic episode they were able to walk with no difficulty and had intact sensation. Functional parameters of these animals fully correlated with the morphologic findings. Widespread acute neuronal injury and vacuolation of neuropil were observed in the control group of animals. In contrast, animals in group B showed much less pronounced morphologic changes after the same period of ischemia. In summary, the combined use of these agents significantly (p < 0.001) reduced the incidence of paraplegia induced by aortic crossclamping with 82% additivity.
Qayumi
A K
AK
Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Janusz
M T
MT
Dorovini-Zis
K
K
Lyster
D M
DM
Jamieson
W R
WR
Poostizadeh
A
A
Feeley
E J
EJ
Nikbakht-Sangari
M
M
D000493:Allopurinol / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001013:Aorta, Thoracic; D003250:Constriction; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D010264:Paraplegia / Q000209:etiology / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013116:Spinal Cord / Q000098:blood supply*; D013552:Swine; D013997:Time Factors
D000493:Allopurinol; D003676:Deferoxamine