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Myocardial β-adrenoceptor density and the distribution of 388-1388-1388-1388-2388-2388-2subpopulations in children with congenital heart disease

  • Cardiology
  • Original Papers
  • Published:
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Abstract

Twenty-six infants and children with congenital heart disease (CHD) undergoing cardiac surgery were investigated for alterations in myocardial β-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 β-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 (K d, ICYP) did not differ statistically between the groups. The proportion of β1- and β1-subpopulation was evaluated by ICI 118,551-[125I]ICYP competition studies. In group II (61.5%) and group III (69.1%) significant lower portions of β1-adrenoceptors were found compared with group I (78.2%). This shift of subpopulations was due to a decreased β1-receptor density while β2-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 β-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 β1-adrenoceptors, is most probably responsible for the shift of the β-adrenoceptor subpopulations from the β1- to β2-subtype, depending on severity and type of cardiac disease.

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Abbreviations

Bmax :

maximum bindings

CHD:

congenital heart disease

Gs :

guanosine triphosphate regulating protein

[125I]ICYP:

[125I] Iodocyanopindolol

K d :

radioligand constant

K d,h :

high affinity β2-component

K d,h :

low affinity β1-component

P Pa/P AO :

ratio between pulmonary and aortic pressure

Q p/Q s :

ratio between pulmonary and systemic blood flow

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Authors and Affiliations

  1. Zentrum für Kinderheilkunde, Heinrich-Heine Universität Düsseldorf, Moorenstrasse 5, W-4000, Düsseldorf 1, Federal Republik of Germany

    H. H. Kramer & H. Wicht

  2. Abteilung für Thorax- und Kardiovaskuläre Chirurgie, Heinrich-Heine Universität Düsseldorf, Moorenstrasse 5, W-4000, Düsseldorf 1, Federal Republik of Germany

    A. Krian & J. Ostermeyer

  3. Kinderpoliklinik der Ludwig-Maximilians-Universität München, Pettenkoferstrasse 8a, W-8000, Munich 2, Federal Republik of Germany

    R. Kozlik & D. Reinhardt

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  1. R. Kozlik
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Kozlik, R., Kramer, H.H., Wicht, H. et al. Myocardial β-adrenoceptor density and the distribution of 388-1388-1388-1388-2388-2388-2subpopulations in children with congenital heart disease. Eur J Pediatr 150, 388–394 (1991). https://doi.org/10.1007/BF02093715

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  • DOI: https://doi.org/10.1007/BF02093715

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