title: Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion.
abstract: BACKGROUND
  We hypothesized that inflammation during spinal cord reperfusion worsens ischemic injury. ATL-146e, an adenosine A(2A) agonist with known anti-inflammatory properties, was used to test this hypothesis at varied intervals to determine the time course of reperfusion injury.
  
  
  METHODS
  Forty rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group (n = 14 animals) received 0.06 microg/kg/min systemic ATL-146e over 3 hours, beginning after 30 minutes of ischemic time. A second group (n = 6 animals) received ATL-146e over 1.5 hours. A third group (n = 3 animals) received ATL-146e over 1 hour, and a fourth group (n = 17 animals) received saline solution. All animals were assessed at 48 hours for hind limb motor function (Tarlov scale, 0-5).
  
  
  RESULTS
  Animals that received ATL-146e for 3 hours (Tarlov score, 4.3 +/- 0.22; P <.001) or 1.5 hours (Tarlov score, 2.7 +/- 0.6; P <.05) had improved neurologic outcomes compared with rabbits that received saline solution (Tarlov score, 0.6 +/- 0.29). Animals that received ATL-146e for 1 hour (Tarlov score, 0.7 +/- 0.8) were not significantly different from those animals that received saline solution.
  
  
  CONCLUSIONS
  Systemic ATL-146e, given during reperfusion, results in time-dependent improvement in spinal cord function after ischemia. This implies that the mechanism of spinal reperfusion injury includes leukocyte-mediated inflammation at a critical post-ischemic time interval.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, The University of Virginia Health System, Charlottesville, VA 22908, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Cassada
authors.forename: C G
authors.initials: CG
authors.lastname: Tribble
authors.forename: A K
authors.initials: AK
authors.lastname: Kaza
authors.forename: S M
authors.initials: SM
authors.lastname: Fiser
authors.forename: S M
authors.initials: SM
authors.lastname: Long
authors.forename: J
authors.initials: J
authors.lastname: Linden
authors.forename: J M
authors.initials: JM
authors.lastname: Rieger
authors.forename: I L
authors.initials: IL
authors.lastname: Kron
authors.forename: J A
authors.initials: JA
authors.lastname: Kern
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D009460:Neurologic Examination; D058906:Purinergic P1 Receptor Agonists; D011687:Purines / Q000494:pharmacology*; D011817:Rabbits; D043705:Receptor, Adenosine A2A; D020127:Recovery of Function / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D013116:Spinal Cord / Q000098:blood supply / Q000473:pathology*; D013525:Surgical Instruments
chemical_list: C431129:ATL 146e; D003509:Cyclohexanecarboxylic Acids; D058906:Purinergic P1 Receptor Agonists; D011687:Purines; D043705:Receptor, Adenosine A2A; D000241:Adenosine