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Objective Adenosine (ADO) is an endogenous nucleoside, which has been involved in blood pressure failure during severe systemic inflammatory response syndrome (severe SIRS) after cardiac surgery with cardiopulmonary bypass (CPB). Adenosine acts via its receptor subtypes, namely A1, A2A, A2B, or A3. Because A2Areceptors are implicated in vascular tone, their expression might contribute to severe SIRS. We compared adenosine plasma levels (APLs) and A2AADO receptor expression (ie, B, K, and mRNA amount) in patients with or without postoperative SIRS.Patients This was a prospective comparative observational study. Forty-four patients who underwent cardiac surgery involving CPB. Ten healthy subjects served as controls.Measurements and Results Among the patients, 11 presented operative vasoplegia and postoperative SIRS (named complicated patients) and 33 were without vasoplegia or SIRS (named uncomplicated patients). Adenosine plasma levels, K, B, and mRNA amount (mean ± SD) were measured on peripheral blood mononuclear cells. Adenosine plasma levels, B, and Kwere significantly higher in complicated patients than in uncomplicated patients (APLs: 2.7 ± 1.0 vs 1.0 ± 0.5 µmol l-1, P< 0.05; B: 210 ± 43 vs 65 ± 26 fmol/mg, P< 0.05; K: 35 ± 10 vs 2 ± 1 nM, P< 0.05). In uncomplicated patients, APLs remain higher than in controls (1 ± 0.5 vs 0.6 ± 0.25 µmol/L; P< 0.05). Mean arterial pressure was inversely correlated to APLs (R = -0.58; P< 0.001) and B(R = -0.64; P< 0.001) leading to an increased requirement of vasoactive drugs during the postoperative period in vasoplegic patients.Conclusions High expression of A2AADO receptor and high APLs may be a predictive factor of postoperative severe SIRS after CPB.