Uncoupling of human cardiac beta-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 beta-adrenoceptors.


RESULTS
We assessed in 12 children with acyanotic congenital heart disease who underwent open-heart surgery right atrial beta-adrenoceptor number and subtype distribution [by (-)-[125I]iodocyanopindolol binding] and adenylate cyclase activation [by the beta-adrenoceptor agonist isoprenaline (100 microM) and by the non-receptor-mediated activators 10 microM GTP, 10 mM NaF, 100 microM forskolin, and 10 mM Mn2+] before and after CPB with cardiac arrest by means of St. Thomas' cardioplegic solution. CPB affected neither beta-adrenoceptor number of subtype distribution nor GTP-, NaF-, forskolin-, or Mn(2+)-induced activation of adenylate cyclase. In contrast, activation of adenylate cyclase by 100 microM isoprenaline was significantly (p = 0.0249) lower after CPB than before CPB.


CONCLUSIONS
CPB with cardioplegic cardiac arrest decreases beta-adrenoceptor-mediated adenylate cyclase activation in a manner compatible with an uncoupling of beta-adrenoceptors from the Gs-protein-adenylate cyclase complex. Such a beta-adrenoceptor desensitization may be the reason why after CPB many patients need inotropic support but do not respond sufficiently to catecholamines.
Schranz
D
D
Department of Internal Medicine, University of Essen, FRG.
Droege
A
A
Broede
A
A
Brodermann
G
G
Schäfer
E
E
Oelert
H
H
Brodde
O E
OE
D000262:Adenylyl Cyclases / Q000378:metabolism; D000293:Adolescent; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D005260:Female; D006324:Heart Arrest, Induced; D006801:Humans; D007223:Infant; D007432:Intraoperative Period; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases