Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion

David C. Cassada, Curtis G. Tribble, Aditya K. Kaza, Steven M. Fiser, Stewart M. Long, Joel Linden, Jayson M. Rieger, Irving L. Kron, John A. Kern

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background. We hypothesized that inflammation during spinal cord reperfusion worsens ischemic injury. ATL-146e, an adenosine A2A agonist with known anti-inflammatory properties, was used to test this hypothesis at varied intervals to determine the time course of reperfusion injury. Methods. Forty rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group (n = 14 animals) received 0.06 μg/kg/min systemic ATL-146e over 3 hours, beginning after 30 minutes of ischemic time. A second group (n = 6 animals) received ATL-146e over 1.5 hours. A third group (n = 3 animals) received ATL-146e over 1 hour, and a fourth group (n = 17 animals) received saline solution. All animals were assessed at 48 hours for hind limb motor function (Tarlov scale, 0-5). Results. Animals that received ATL-146e for 3 hours (Tarlov score, 4.3 ± 0.22; P < .001) or 1.5 hours (Tarlov score, 2.7 ± 0.6; P < .05) had improved neurologic outcomes compared with rabbits that received saline solution (Tarlov score, 0.6 ± 0.29). Animals that received ATL-146e for 1 hour (Tarlov score, 0.7 ± 0.8) were not significantly different from those animals that received saline solution. Conclusions. Systemic ATL-146e, given during reperfusion, results in time-dependent improvement in spinal cord function after ischemia. This implies that the mechanism of spinal reperfusion injury includes leukocyte-mediated inflammation at a critical post-ischemic time interval.

Original languageEnglish (US)
Pages (from-to)230-235
Number of pages6
JournalSurgery
Volume130
Issue number2
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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    Cassada, D. C., Tribble, C. G., Kaza, A. K., Fiser, S. M., Long, S. M., Linden, J., Rieger, J. M., Kron, I. L., & Kern, J. A. (2001). Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. Surgery, 130(2), 230-235. https://doi.org/10.1067/msy.2001.115838