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

Abstract

BACKGROUND:

We hypothesized that inflammation during spinal cord reperfusion worsens ischemic injury. ATL-146e, an adenosine A(2A) 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 microg/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.

• Authors: D C Cassada, C G Tribble, A K Kaza, S M Fiser, S M Long, J Linden, J M Rieger, I L Kron, J A Kern
• Journal: Surgery (Surgery) Vol. 130 Issue 2 Pg. 230-5 (Aug 2001) ISSN: 0039-6060 [Print] United States
• PMID: 11490354 (Publication Type: Journal Article)

Chemical References

• ATL 146e
• Cyclohexanecarboxylic Acids
• Purinergic P1 Receptor Agonists
• Purines
• Receptor, Adenosine A2A
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Animals
• Aorta, Thoracic
• Cyclohexanecarboxylic Acids (pharmacology)
• Disease Models, Animal
• Drug Administration Schedule
• Neurologic Examination
• Purinergic P1 Receptor Agonists
• Purines (pharmacology)
• Rabbits
• Receptor, Adenosine A2A
• Recovery of Function (drug effects)
• Reperfusion Injury (drug therapy, pathology)
• Spinal Cord (blood supply, pathology)
• Surgical Instruments