Adenosine A2A Activation Attenuates Nontransplantation Lung Reperfusion Injury

• Published in: The Journal of surgical research Vol. 149; no. 1; pp. 3 - 8
• Main Authors: Ellman, Peter I., M.D, Reece, T. Brett, M.D, Law, Marianna G., M.D, Gazoni, Leo M., M.D, Singh, Ramesh, M.D, Laubach, Victor E., Ph.D, Linden, Joel, Ph.D, Tribble, Curtis G., M.D, Kron, Irving L., M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01.09.2008
• Subjects: Adenosine A2 Receptor Agonists; Animals; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; Constriction; Cyclohexanecarboxylic Acids - therapeutic use; Disease Models, Animal; General aspects; Lung - surgery; Lung Diseases - drug therapy; Male; Medical sciences; Purines - therapeutic use; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Surgery; adenosine; adenosine A 2A; lung reperfusion injury; Medicine; Lung disease; Purine nucleoside; Adenosine; Reperfusion; Treatment; Respiratory disease; Surgery; adenosine A2A; Activation
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2007.08.008

Background Lung reperfusion injury is a significant problem in cardiothoracic surgery. Previous studies have demonstrated that an adenosine A2A agonist can attenuate lung reperfusion injury in a lung transplantation model. There has been little work, however, examining its effects in the setting of nontransplant ischemia reperfusion. Our hypothesis was that an A2A agonist would attenuate lung reperfusion injury in a warm ischemia hilar clamping model. Study design Sprague Dawley rats underwent 90 min of left hilar clamping followed by 4 h of reperfusion. Group 1 ( n = 13) received an intravenous infusion of 0.06 ug/kg/min of ATL-146e, which was started 10 min before reperfusion. Group 2 ( n = 16) received an equivalent saline infusion. A third sham group ( n = 14) received the same protocol as Group 2 but no lung ischemia. Results Animals receiving ATL-146e showed significant improvements in oxygenation (Group 1: 447 ± 26.02 mmHg versus Group 2: 223 ± 24.46 mmHg ( P < 0.001) as well as ventilation (pCO2 Group 1: 48.78 ± 3.88 versus Group 2: 63.56 ± 4.80 ( P = 0.009)). Total protein in the bronchoalveolar lavage was significantly higher in the saline group compared with the adenosine as well as a higher proportion of neutrophils. Histological analysis demonstrated a significantly higher number of neutrophils in the IR group compared with the adenosine group. Conclusions ATL-146e, an adenosine analogue that is a specific agonist for the A2A receptor, attenuates reperfusion injury in an in vivo rat lung model. Arterial blood gas measurements demonstrate a statistically significant increase in oxygenation and improved ventilation.