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 Citations (Scopus)

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

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Reperfusion Injury
Spinal Cord Injuries
Adenosine
Sodium Chloride
Reperfusion
Myelitis
Rabbits
Spinal Injuries
ATL 146e
Constriction
Nervous System
Aorta
Spinal Cord
Leukocytes
Anti-Inflammatory Agents
Ischemia
Extremities
Inflammation
Wounds and Injuries

ASJC Scopus subject areas

  • Surgery

Cite this

Cassada, D. C., Tribble, C. G., Kaza, A. K., Fiser, S. M., Long, S. M., Linden, J., ... 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

Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. / Cassada, David C.; Tribble, Curtis G.; Kaza, Aditya K.; Fiser, Steven M.; Long, Stewart M.; Linden, Joel; Rieger, Jayson M.; Kron, Irving L.; Kern, John A.

In: Surgery, Vol. 130, No. 2, 01.01.2001, p. 230-235.

Research output: Contribution to journalArticle

Cassada, DC, Tribble, CG, Kaza, AK, Fiser, SM, Long, SM, Linden, J, Rieger, JM, Kron, IL & Kern, JA 2001, 'Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion', Surgery, vol. 130, no. 2, pp. 230-235. https://doi.org/10.1067/msy.2001.115838
Cassada DC, Tribble CG, Kaza AK, Fiser SM, Long SM, Linden J et al. Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. Surgery. 2001 Jan 1;130(2):230-235. https://doi.org/10.1067/msy.2001.115838
Cassada, David C. ; Tribble, Curtis G. ; Kaza, Aditya K. ; Fiser, Steven M. ; Long, Stewart M. ; Linden, Joel ; Rieger, Jayson M. ; Kron, Irving L. ; Kern, John A. / Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. In: Surgery. 2001 ; Vol. 130, No. 2. pp. 230-235.
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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.",
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AU - Tribble, Curtis G.

AU - Kaza, Aditya K.

AU - Fiser, Steven M.

AU - Long, Stewart M.

AU - Linden, Joel

AU - Rieger, Jayson M.

AU - Kron, Irving L.

AU - Kern, John A.

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N2 - 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.

AB - 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.

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