Systemic adenosine A2A agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord

被引:34
作者
Cassada, DC
Gangemi, JJ
Rieger, JM
Linden, J
Kaza, AK
Long, SM
Kron, IL
Tribble, CG
Kern, JA
机构
[1] Univ Virginia, Hlth Sci Ctr, Dept Surg, Hlth Syst, Charlottesville, VA 22908 USA
[2] Univ Virginia, Div Thorac & Cardiovasc Surg, Hlth Syst, Charlottesville, VA 22908 USA
[3] Univ Virginia, Dept Mol Physiol, Hlth Syst, Charlottesville, VA 22908 USA
[4] Univ Virginia, Dept Chem, Coll Arts & Sci, Charlottesville, VA 22903 USA
关键词
D O I
10.1016/S0003-4975(01)03057-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. The adenosine A(2A) agonist ATL-146e (4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-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 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, 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. (C) 2001 by The Society of Thoracic Surgeons.
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页码:1245 / 1250
页数:6
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