Adenosine A2A receptor activation decreases reperfusion injury associated with high-flow reperfusion

Steven M. Fiser, Curtis G. Tribble, Aditya K. Kaza, Stewart M. Long, John A. Kern, David C. Cassada, Joel Linden, Jayson Rieger, Victor E. Laubach, Andy Matisoff, Irving L. Kron

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Introduction: High pulmonary artery flow rates can result in severe reperfusion injury after lung transplantation. Our hypothesis was that selective activation of the adenosine A2A 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 μg · 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 A2A receptor analogue ATL-146e significantly decreases the severity of reperfusion injury in the setting of both high-flow and controlled high-flow reperfusion.

Original languageEnglish (US)
Pages (from-to)973-978
Number of pages6
JournalJournal of Thoracic and Cardiovascular Surgery
Volume124
Issue number5
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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    Fiser, S. M., Tribble, C. G., Kaza, A. K., Long, S. M., Kern, J. A., Cassada, D. C., Linden, J., Rieger, J., Laubach, V. E., Matisoff, A., & Kron, I. L. (2002). Adenosine A2A receptor activation decreases reperfusion injury associated with high-flow reperfusion. Journal of Thoracic and Cardiovascular Surgery, 124(5), 973-978. https://doi.org/10.1067/mtc.2002.124886