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Thirteen patients undergoing cardiac surgery were studied to examine whether β-adrenergic desensitization occurs in the perioperative period surrounding cardiac surgery, using peripheral blood lymphocytes as a model. Lymphocytes were isolated before induction of anesthesia (PRE) and on the morning of the first postoperative day (POST). Cyclic adenosine monophosphate (cAMP) production from the lymphocytes was assayed in the untreated (BASAL) state, and after treatment with 5 μM isoproterenol, 10 μM prostaglandin E1, or 20 mM sodium fluoride with 10 μM AlCl3 (NaF). All cAMP values are reported as picomoles per 106 cells, mean ± SEM. BASAL cAMP production did not change significantly between the PRE and POST samples (PRE, 1.2 ± 0.1; POST, 1.0 ± 0.1). Isoproterenol-stimulated cAMP was significantly lower postoperatively (PRE, 8.36 ± 0.9; POST, 5.1 ± 0.5; P < 0.005). Prostaglandin E1-stimulated cAMP did not change (PRE, 21.7 ± 2.4; POST, 25.3 ± 2.5), and NaF-stimulated cAMP was increased postoperatively (PRE, 8.8 ± 1.6; POST, 14.3 ± 2.0; P < 0.05). These findings suggest that cardiac surgery and/or cardiopulmonary bypass results in significant desensitization of the β-adrenergic receptor/adenylate cyclase system of lymphocytes, which may parallel changes in the adrenergic response of other organ systems.