Early adenosine receptor activation ameliorates spinal cord reperfusion injury.

Abstract

OBJECTIVES:

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.

• Authors: T Brett Reece, Curtis G Tribble, David O Okonkwo, Jonathon D Davis, Thomas S Maxey, Leo M Gazoni, Joel Linden, Irving L Kron, John A Kern
• Journal: Journal of cardiovascular medicine (Hagerstown, Md.) (J Cardiovasc Med (Hagerstown)) Vol. 9 Issue 4 Pg. 363-7 (Apr 2008) ISSN: 1558-2027 [Print] United States
• PMID: 18334890 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ATL 146e
• Cyclohexanecarboxylic Acids
• Purines
• Receptor, Adenosine A2A

Topics

• Analysis of Variance
• Animals
• Cyclohexanecarboxylic Acids (pharmacology)
• Disease Models, Animal
• Hemodynamics
• Purines (pharmacology)
• Rabbits
• Receptor, Adenosine A2A
• Recovery of Function (drug effects)
• Reperfusion Injury (drug therapy, pathology)
• Spinal Cord (blood supply, pathology)
• Statistics, Nonparametric