title: Adenosine A2A receptor activation decreases reperfusion injury associated with high-flow reperfusion.
abstract: BACKGROUND
  High pulmonary artery flow rates can result in severe reperfusion injury after lung transplantation. Our hypothesis was that selective activation of the adenosine A(2A) receptor with a highly specific analog (ATL-146e) would inhibit leukocyte activation and decrease reperfusion injury after high-flow reperfusion.
  
  
  METHODS
  Using our isolated, ventilated, blood-perfused rabbit lung model, all groups (n = 8 per group) underwent lung harvest, 4 hours of cold storage, and blood reperfusion for 30 minutes. Measurements of pulmonary artery pressure (in millimeters of mercury), arterial oxygenation (in millimeters of mercury), myeloperoxidase, peak inspiratory pressure, and wet/dry weight ratio were obtained. Groups 1 (high flow) and 2 (high flow ATL-146e) underwent reperfusion at 120 mL/min for 30 minutes. Groups 3 (controlled high flow) and 4 (controlled high flow ATL-146e) underwent controlled reperfusion with an initial reperfusion of 60 mL/min for the first 5 minutes, followed by a rate of 120 mL/min for 25 minutes. During reperfusion, groups 2 and 4 received ATL-146e at 4 microg. kg(-1). min(-1).
  
  
  RESULTS
  ATL-146e significantly improved lung physiologic measurements under both high-flow (group 1 vs group 2) and controlled high-flow (group 3 vs group 4) conditions after 30 minutes.
  
  
  CONCLUSIONS
  The adenosine A(2A) receptor analogue ATL-146e significantly decreases the severity of reperfusion injury in the setting of both high-flow and controlled high-flow reperfusion.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA. smf9e@virginia.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Fiser
authors.forename: Curtis G
authors.initials: CG
authors.lastname: Tribble
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Kaza
authors.forename: Stewart M
authors.initials: SM
authors.lastname: Long
authors.forename: John A
authors.initials: JA
authors.lastname: Kern
authors.forename: David C
authors.initials: DC
authors.lastname: Cassada
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Jayson
authors.initials: J
authors.lastname: Rieger
authors.forename: Victor E
authors.initials: VE
authors.lastname: Laubach
authors.forename: Andy
authors.initials: A
authors.lastname: Matisoff
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D008168:Lung / Q000201:enzymology / Q000378:metabolism / Q000601:surgery; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D011651:Pulmonary Artery / Q000737:chemistry / Q000473:pathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines / Q000494:pharmacology*; D011817:Rabbits; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000627:therapeutic use*; D015424:Reperfusion / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D013997:Time Factors
chemical_list: C431129:ATL 146e; D003509:Cyclohexanecarboxylic Acids; D011687:Purines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D009195:Peroxidase