Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion.
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.
Cassada
D C
DC
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, The University of Virginia Health System, Charlottesville, VA 22908, USA.
Tribble
C G
CG
Kaza
A K
AK
Fiser
S M
SM
Long
S M
SM
Linden
J
J
Rieger
J M
JM
Kron
I L
IL
Kern
J A
JA
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
C431129:ATL 146e; D003509:Cyclohexanecarboxylic Acids; D058906:Purinergic P1 Receptor Agonists; D011687:Purines; D043705:Receptor, Adenosine A2A; D000241:Adenosine