Desensitization of Myocardial /3-Adrenergic Receptors During Cardiopulmonary Bypass Evidence for Early Uncoupling and Late Downregulation

surgery, is a potent stimulant to the release of endogenous catecholamines. Hence, we tested the hypothesis that CPB results in myocardial P-adrenergic receptor (PAR) desensitization. Methods and Results. We obtained canine transmyocardial left ventricular biopsies before, during (155 minutes), and after CPB (pre-CPB, CPB, and post-CPB, respectively) and determined PAR density, proportion of f1AR to I2AR, and PAR coupling capacity to adenylyl cyclase. PAR density was stable at 112±14 fmol/mg (pre-CPB) and 103±9 fmol/mg (CPB) but decreased post-CPB to 84+7 fmol/mg. The ratio of ,31AR to .32AR (determined by two-site fit for [1251]-iodocyanopindolol competition binding with the fI1AR selective antagonist 1C189.406) remained constant throughout (60+3:40±3 pre-CPB, 55±3:44±3 CPB, and 61±2:39±2 post-CPB), revealing that both P1AR and R2AR subtypes were downregulated. A different pattern was noted in the functional properties of these receptors during CPB. Decreased maximal isoproterenol-stimulated adenylyl cyclase activity (252±14 to 216±12 pmol/30 min/ mg), submaximal isoproterenol-stimulated adenylyl cyclase activity (183±+10 to 157±+11 pmol/30 min/mg), and zinterol-stimulated adenylyl cyclase activity (187+±11 to 159±+11 pmol/30 min/mg, a measure of f2AR subtype activation) were noted during CPB, at the time when weaning from CPB takes place. However, this desensitized pattern was found to be completely reversed by 30 minutes post-CPB, with adenylyl cyclase activities returning to pre-CPB levels