Comparison of systemic and retrograde delivery of adenosine A2A agonist for attenuation of spinal cord injury after thoracic aortic cross-clamping.
BACKGROUND
Paraplegia remains a devastating complication of thoracic aortic surgery, which has been attenuated by retrograde adenosine and systemic adenosine A2A receptor activation. We hypothesized that despite retrograde spinal perfusion of an adenosine A2A agonist (ATL-146e), systemic therapy produces superior spinal cord protection with reduced inflammation.


METHODS
Forty pigs underwent 30-minute thoracic aortic cross-clamping. Pigs received: no therapy (control); retrograde saline (retrograde control); retrograde ATL-146e; systemic ATL-146e; systemic ATL-146e with retrograde saline; or systemic and retrograde ATL-146e. Retrograde therapies were given during ischemia. Systemic ATL-146e (0.06 microg.kg(-1).min(-1)) was given intravenously for 3 hours at reperfusion. At 24 hours, motor function was assessed using the Tarlov scale. Tissue was analyzed for neuronal viability, microtubule-associated protein-2 expression, and neutrophil sequestration (myeloperoxidase activity).


RESULTS
Four pigs received retrograde barium showing both radiographic and histologic spinal cord perfusion. Tarlov scores at 24 hours were significantly improved versus both control groups in all ATL groups except the combined ATL-146e group (all p < 0.05). Neuronal viability by hematoxylin and eosin stain was significantly preserved in systemic ATL groups compared with both control groups (all p < 0.05). Microtubule-associated protein-2 expression was significantly preserved compared with both control groups in all systemic ATL groups. Systemic ATL significantly lowered myeloperoxidase activity versus both control groups (p < 0.01).


CONCLUSIONS
Both retrograde and systemic ATL-146e therapies attenuate ischemic spinal cord injury, but combining the two routes was less effective. Given comparable results between the two routes and the simplicity of systemic delivery, peripheral venous ATL-146e at reperfusion should be preferred for spinal cord protection in thoracic aortic surgery.
Department of Surgery, University of Virginia, Charlottesville, Virginia, USA. tbr5q@virginia.edu
T Brett
TB
Reece
David O
DO
Okonkwo
Peter I
PI
Ellman
Thomas S
TS
Maxey
Carlos
C
Tache-Leon
Patrick S
PS
Warren
Jeffrey J
JJ
Laurent
Joel
J
Linden
Irving L
IL
Kron
Curtis G
CG
Tribble
John A
JA
Kern
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D006429:Hemiplegia / Q000517:prevention & control; D006614:Hindlimb / Q000502:physiology; D023421:Models, Animal; D011183:Postoperative Complications / Q000517:prevention & control; D011687:Purines / Q000627:therapeutic use*; D011859:Radiography; D013116:Spinal Cord / Q000000981:diagnostic imaging; D013119:Spinal Cord Injuries / Q000517:prevention & control*; D013552:Swine
C431129:ATL 146e; D058908:Adenosine A2 Receptor Agonists; D003509:Cyclohexanecarboxylic Acids; D011687:Purines