Adenosine A2A activation attenuates nontransplantation lung reperfusion injury.
BACKGROUND
Lung reperfusion injury is a significant problem in cardiothoracic surgery. Previous studies have demonstrated that an adenosine A(2A) 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 A(2A) agonist would attenuate lung reperfusion injury in a warm ischemia hilar clamping model.


METHODS
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 A(2A) 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.
Ellman
Peter I
PI
Department of Surgery, University of Virginia, Charlottesville, Virginia 22908, USA. pie8y@virginia.edu
Reece
T Brett
TB
Law
Marianna G
MG
Gazoni
Leo M
LM
Singh
Ramesh
R
Laubach
Victor E
VE
Linden
Joel
J
Tribble
Curtis G
CG
Kron
Irving L
IL
D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003250:Constriction; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008168:Lung / Q000601:surgery; D008171:Lung Diseases / Q000188:drug therapy*; D008297:Male; D011687:Purines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*
C431129:ATL 146e; D058908:Adenosine A2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D003509:Cyclohexanecarboxylic Acids; D011687:Purines