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Ann Thorac Surg 2002;74:846-850
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Adenosine A_2A agonist reduces paralysis after spinal cord ischemia: correlation with A_2A receptor expression on motor neurons¹

^a Division of Vascular and Endovascular Surgery, University of Tennessee Medical Center, Knoxville, Tennessee, USA
^b Division of Thoracic and Cardiovascular Surgery, Departments of Surgery and Molecular Pharmacology, University of Virginia Health System, and Department of Chemistry, University of Virginia, Charlottesville, Virginia, USA

* Address reprint requests to Dr Kern, Department of Surgery, Box 181-95, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
e-mail: jak3r{at}virginia.edu

Presented at the Forty-eighth Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 8–10, 2001.

Background. The adenosine A_2A agonist ATL-146e ameliorates reperfusion inflammation, reducing subsequent paralysis and neuronal apoptosis after spinal cord ischemia. We hypothesized that neuroprotection with ATL-146e involves inducible neuronal adenosine A_2A receptors (A_2A-R) that are upregulated after ischemia.

Methods. Eighteen rabbits underwent laparotomy, and 14 sustained spinal cord ischemia from cross-clamping the infrarenal aorta for 45 minutes. One group (ischemia-reperfusion [I/R] + ATL) received ATL-146e intravenously for 3 hours during spinal cord reperfusion. A second group (I/R) received equivolume intravenous saline solution for 3 hours and served as an ischemic control, and a third group (Sham) underwent sham laparotomy. At 48 hours, all subjects were assessed for motor impairment using the Tarlov scoring system (0 to 5). Lumbar spinal cord sections were immunolabeled for A_2A-R and graded in a blinded fashion using light microscopy.

Results. There was a significant improvement in Tarlov scores in I/R + ATL animals compared with the I/R group. Sham-operated animals demonstrated no A_2A-R immunoreactivity. There was a dramatic increase in A_2A-R immunoreactivity in neurons of lumbar spinal cord sections from I/R compared with I/R + ATL and sham-operated animals.

Conclusions. Reduction in paralysis in animals receiving ATL-146e correlates with the new finding of A_2A-R expression on lumbar spinal cord motor neurons after ischemia. Adenosine A_2A agonists may exert neuroprotective effects by binding to inducible neuronal A_2A-R that are upregulated during spinal cord reperfusion, and reduced in response to administration of an A_2A-R-specific agonist.

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