Systemic adenosine A(2A) agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord

Background. The adenosine A(2A) agonist ATL-146e (4-{3-[6-Amino-9-(5-ethylc arbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}- cyclohexanecarboxylic acid methyl ester) has been shown to prevent reperfus ion injury in multiple organ systems through inhibition of activated leukoc yte-endothelial interaction. We hypothesized that systemic ATL-146e could r educe spinal cord reperfusion injury after aortic clamping. Methods. Twenty-six rabbits underwent crossclamping of the infrarenal aorta for 45 minutes. One group received intravenous ATL-146e for 3 hours during reperfusion. A second cohort received only vehicle and served as controls. Animals were assessed at 24 and 48 hours using the Tarlov (0 to 5) scoring system for hind limb function. To evaluate neuronal attrition, immunostain ing of lumbar spinal cord sections was performed using anti-SMI 33 antibody against neurofilament. Results. Systemic ATL-146e was tolerated without hemodynamic lability. Anim als that received ATL-146e had significantly improved neurologic outcomes 2 4 and 48 hours after spinal cord ischemia (p < 0.001). There was preservati on of neuronal architecture in the ventral horn of spinal cord sections fro m animals receiving ATL-146e compared with control animals. Conclusions. Intravenous ATL-146e given during reperfusion is tolerated wit hout hemodynamic lability, and results in substantially improved spinal cor d function after ischemia. by preservation of ventral horn neurons. (C) 200 1 by The Society of Thoracic Surgeons.