Comparison of systemic and retrograde delivery of adenosine A2A agonist for attenuation of spinal cord injury after thoracic aortic cross-clamping
| Autor: | David O. Okonkwo, Peter I. Ellman, T. Brett Reece, Curtis G. Tribble, Patrick S. Warren, Joel Linden, Irving L. Kron, Carlos Tache-Leon, Jeffrey J. Laurent, John A. Kern, Thomas S. Maxey |
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| Rok vydání: | 2005 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adenosine A2 Receptor Agonists Cyclohexanecarboxylic Acids Swine Ischemia Aorta Thoracic Hemiplegia Central nervous system disease Postoperative Complications hemic and lymphatic diseases medicine.artery medicine Animals Spinal cord injury Spinal Cord Injuries Aorta business.industry medicine.disease Spinal cord Adenosine Hindlimb Radiography medicine.anatomical_structure Spinal Cord Purines Anesthesia Models Animal Surgery Cardiology and Cardiovascular Medicine business Paraplegia Perfusion medicine.drug |
| Zdroj: | The Annals of thoracic surgery. 81(3) |
| ISSN: | 1552-6259 |
| Popis: | 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.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).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 p0.05). Neuronal viability by hematoxylin and eosin stain was significantly preserved in systemic ATL groups compared with both control groups (all p0.05). 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 (p0.01).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. |
| Databáze: | OpenAIRE |
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