Systemic adenosine A2A agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord.
BACKGROUND
The adenosine A2A agonist ATL-146e (4-[3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxytetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester) has been shown to prevent reperfusion injury in multiple organ systems through inhibition of activated leukocyte-endothelial interaction. We hypothesized that systemic ATL-146e could reduce spinal cord reperfusion injury after aortic clamping.


METHODS
Twenty-six rabbits underwent cross-clamping 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, immunostaining of lumbar spinal cord sections was performed using anti-SMI 33 antibody against neurofilament.


RESULTS
Systemic ATL-146e was tolerated without hemodynamic lability. Animals that received ATL-146e had significantly improved neurologic outcomes 24 and 48 hours after spinal cord ischemia (p < 0.001). There was preservation of neuronal architecture in the ventral horn of spinal cord sections from animals receiving ATL-146e compared with control animals.


CONCLUSIONS
Intravenous ATL-146e given during reperfusion is tolerated without hemodynamic lability, and results in substantially improved spinal cord function after ischemia by preservation of ventral horn neurons.
Cassada
D C
DC
Department of Surgery, The University of Virginia Health System, Charlottesville 22908, USA.
Gangemi
J J
JJ
Rieger
J M
JM
Linden
J
J
Kaza
A K
AK
Long
S M
SM
Kron
I L
IL
Tribble
C G
CG
Kern
J A
JA
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D009460:Neurologic Examination / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D058906:Purinergic P1 Receptor Agonists; D011687:Purines / Q000494:pharmacology*; D011817:Rabbits; D043705:Receptor, Adenosine A2A; D015427:Reperfusion Injury / Q000473:pathology*; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000473:pathology*
C431129:ATL 146e; D003509:Cyclohexanecarboxylic Acids; D058906:Purinergic P1 Receptor Agonists; D011687:Purines; D043705:Receptor, Adenosine A2A