Uncoupling of Human Cardiac ,-Adrenoceptors During Cardiopulmonary Bypass With Cardioplegic Cardiac Arrest

Background. It is well known that during cardiopulmonary bypass (CPB) with cardioplegic cardiac arrest, catecholamines are vigorously increased. We therefore investigated whether this might cause desensitization of human cardiac 8-adrenoceptors. Methods and Results. We assessed in 12 children with acyanotic congenital heart disease who underwent open-heart surgery right atrial P-adrenoceptor number and subtype distribution [by (-)-["~I]iodocyanopindolol binding] and adenylate cyclase activation [by the f-adrenoceptor agonist isoprenaline (100 l M) and by the non-receptor-mediated activators 10 ,LM GTP, 10 mM NaF, 100 ,uM forskolin, and 10 mM Mn2'] before and after CPB with cardiac arrest by means of St. Thomas' cardioplegic solution. CPB affected neither 3-adrenoceptor number or subtype distribution nor GTP-, NaF-, forskolin-, or Mn2+induced activation of adenylate cyclase. In contrast, activation of adenylate cyclase by 100 ,uM isoprenaline was significantly (p=0.0249) lower after CPB than before CPB. Conclusions. CPB with cardioplegic cardiac arrest decreases P-adrenoceptor-mediated adenylate cyclase activation in a manner compatible with an uncoupling of 3-adrenoceptors from the G,-protein-adenylate cyclase complex. Such a f3adrenoceptor desensitization may be the reason why after CPB many patients need inotropic support but do not respond sufficiently to catecholamines. (Circulation 1993;87:422-426)