Myocardial beta-adrenoceptor density and the distribution of beta 1- 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-[125I]Iodocyanopindolol [( 125I]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 (Kd.ICYP) did not differ statistically between the groups. The proportion of beta 1- and beta 2-subpopulations was evaluated by ICI 118,551-[125I]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.(ABSTRACT TRUNCATED AT 250 WORDS)
Kozlik
R
R
Kinderpoliklinik, Ludwig-Maximilians-Universität München, Federal Republik of Germany.
Kramer
H H
HH
Wicht
H
H
Krian
A
A
Ostermeyer
J
J
Reinhardt
D
D
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003490:Cyanosis / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004837:Epinephrine / Q000097:blood; D006330:Heart Defects, Congenital / Q000097:blood / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D020120:Iodocyanopindolol; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D009638:Norepinephrine; D004837:Epinephrine