MYOCARDIAL BETA-ADRENOCEPTOR DENSITY AND THE DISTRIBUTION OF BETA-1-ADRENOCEPTOR AND BETA-2-ADRENOCEPTOR SUBPOPULATIONS IN CHILDREN WITH CONGENITAL HEART-DISEASE

Twenty-six infants and children with congenital heart disease (CHD) undergoing cardiac surgery were investigated for alterations in myocardial beta-adrenoceptor density. The patients were divided into three groups according to type and severity of CHD: group I consisted of 6 patients with acyanotic shunt lesions of moderate severity; group II comprised 13 children with severe acyanotic shunt and valve lesions and group III included 7 children with cyanotic CHD. The myocardial beta-adrenoceptor density was determined using (-)3-[I-125]Iodocyanopindolo ([I-125]ICYP) and was reduced by approximately 50% in severe acyanotic CHD (33.6 fmol/mg protein) and cyanotic CHD (35.3 fmol/mg protein) in comparison with the group with less severe acyanotic shunt defects (64.4 fmol/mg protein). The affinity dissociation constant (K(d, ICYP)) did not differ statistically between the groups. The proportion of beta-1- and beta-2-subpopulations was evaluated by ICI 118,551-[I-125]ICYP competition studies. In group II (61.5%) and group III (69.1%) significant lower portions of beta-1-adrenoceptors were found compared with group I (78.2%). This shift of subpopulations was due to a decreased beta-1-receptor density while beta-2-receptor density was unchanged in all groups. While the plasma noradrenaline levels of group I were similar to those of a control group of 13 healthy children, respective values of group II and III were significantly elevated. A significant negative correlation was found between plasma noradrenaline levels and myocardial beta-adrenoceptor density. It is concluded that exposure of these receptors to increased circulating catecholamines, due to an enhanced sympathetic tone, leads to a reduction of their density. Noradrenaline, a preferential agonist of beta-1-adrenoceptors, is most probably responsible for the shift of the beta-adrenocetor subpopulations from the beta-1- to beta-2-subtype, depending on severity and type of cardiac disease.