DOWN-REGULATION AND DESENSITIZATION OF THE BETA-ADRENERGIC-RECEPTOR SYSTEM OF HUMAN-LYMPHOCYTES AFTER CARDIAC-SURGERY

We used the beta-adrenergic receptor (betaAR) system of human lymphocytes as a model to examine perioperative adrenergic regulation in 12 patients undergoing coronary artery bypass grafting and 12 patients undergoing mitral or aortic valve replacement. BetaAR function was assessed by measuring cyclic adenosine monophosphate (cAMP) production in the unstimulated state and in response to maximal stimulation by isoproterenol and prostaglandin E1. Receptor number and dissociation constant (K(D)) were assessed with [I-125]iodopindolol. In the valve surgery patients, basal, isoproterenol-stimulated, and prostaglandin E1-stimulated cAMP production were significantly decreased postoperatively, by 39%, 55%, and 24%, respectively. BetaAR number decreased from a mean of 1333 +/- 143 sites/cell to 897 +/- 56 sites/cell postoperatively, whereas the K(D) increased from 12.9 +/- 1.1 pM to 37.0 +/- 7.3 pM. In the coronary artery bypass graft patients, there were no significant alterations in cAMP production or receptor number, but the K(D) increased from 19.8 +/- 2.9 pM to 57.5 +/- 11.8 pM. These findings suggest that cardiac surgery and/or cardiopulmonary bypass may result in significant down-regulation and desensitization of the betaAR system of lymphocytes, which may parallel alterations in other organ systems.