Early adenosine receptor activation ameliorates spinal cord reperfusion injury.
OBJECTIVE
Adenosine receptor activation at reperfusion has been shown to ameliorate ischemia-reperfusion injury of the spinal cord, but the effects of therapy given in response to ischemic injury are unknown. We hypothesized that adenosine receptor activation with ATL-146e would produce similar protection from ischemic spinal cord injury, whether given at reperfusion or in a delayed fashion.


METHODS
Twenty-two New Zealand white rabbits were divided into three groups. All three groups, including the ischemia-reperfusion group (IR, n = 8), underwent 45 min of infrarenal aortic occlusion. The early treatment group (early, n = 8) received 0.06 mug/kg/min of ATL-146e for 3 h beginning 10 min prior to reperfusion. The delayed treatment group (delayed, n = 6) received ATL-146e starting 1 h after reperfusion. After 48 h, hind limb function was graded using the Tarlov score. Finally, lumbar spinal cord neuronal cytoarchitecture was evaluated.


RESULTS
Hemodynamic parameters were similar among the groups. Hind limb function at 48 h was significantly better in the early group (3.5 +/- 1.0) compared to the IR group (0.625 +/- 0.5, P < or = 0.01). There was a trend towards better hind limb function in the early group compared to the delayed group (2.4 +/- 1.1, P = 0.08). Hind limb function was similar between delayed and IR groups. Hematoxylin-eosin spinal cord sections demonstrated preservation of viable motor neurons in the early group compared to the delayed and IR groups.


CONCLUSIONS
Early therapy with ATL-146e provided better protection in this study; therefore, therapy should not be delayed until there is evidence of ischemic neurological deficit. This study suggests that adenosine receptor activation is most effective as a preventive strategy at reperfusion for optimal protection in spinal cord ischemia-reperfusion injury.
Reece
T Brett
TB
Department of Surgery, University of Virginia, Charlottesville, Virginia, USA. brett.reece@UCHSC.edu
Tribble
Curtis G
CG
Okonkwo
David O
DO
Davis
Jonathon D
JD
Maxey
Thomas S
TS
Gazoni
Leo M
LM
Linden
Joel
J
Kron
Irving L
IL
Kern
John A
JA
D000704:Analysis of Variance; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D006439:Hemodynamics; 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*; D018709:Statistics, Nonparametric
C431129:ATL 146e; D003509:Cyclohexanecarboxylic Acids; D011687:Purines; D043705:Receptor, Adenosine A2A