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 mug/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<plus/minus>0.6; P<.05) had improved neurologic outcomes compared with rabbits that received saline solution (Tarlov score, 0.6<plus/minus>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.