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Objective: To assess the safety of regadenoson, a selective agonist of A2A adenosine receptors, combined with low-level exercise in subjects with severe chronic obstructive pulmonary disease (COPD), referred for myocardial perfusion imaging (MPI)., Methods: We studied prospectively 12 male patients with severe COPD. Stress was 4min of low-level exercise with bolus injection of regadenoson (0.4mg) at 1.5min, followed by (99m)Tc-MPI agent injection. Demographics, medical history, lung medications, adverse events, oxygen saturation (SatO2), MPI findings for coronary artery disease (CAD), and changes in systolic blood pressure (SBP), and heart rate (HR) were registered., Results: The observed adverse event profile of regadenoson was similar to that of patients with mild-moderate COPD. There was no clinical exacerbation of COPD. Adverse events were self-limiting: dyspnea (33.3%), fatigue (25.0%), chest pain, headache (16.7%, respectively), and gastrointestinal discomfort, dry mouth, flushing, feeling hot and dizziness (8.3%, respectively). 25.0% of patients did not report any symptoms. We observed significant increases in SBP and HR from baseline (142.6mmHg±22.3 vs 152.5mmHg±18.5, and 80 b.p.m.±18 vs 105 b.p.m.±22, respectively; p<0.05)., Conclusions: Regadenoson combined with low-level exercise is safe and well tolerated in stable patients with severe COPD undergoing MPI., (Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.)