Cardiotoxicity of ß-mimetic catecholamines during ontogenetic development - possible risks of antenatal therapy.

Catecholamines are involved in the regulation of a wide variety of vital functions. The ß-adrenergic receptor (ß-AR) - adenylyl cyclase system has been identified early in embryogenesis before the heart has received adrenergic innervation. The structure of ß-receptors in the immature myocardium is similar to that in adults; there are, however, significant quantitative developmental changes in the inotropic and chronotropic responsiveness. Information on the toxic effect of the ß-AR agonists in the immature heart is surprisingly scarce, even though these agents are used in clinical practice both during pregnancy and in early postnatal development. Large doses of ß-AR agonists induce malformations of the cardiovascular system; the type of change depends upon the time at which the ß-AR agonist was administered during embryogenesis. During postnatal ontogeny, the cardiotoxicity of ß-AR agonists increased from birth to adulthood. It seems likely that despite interspecies differences, developmental changes in the cardiac sensitivity to ß-AR agonists may exist in all mammals, depending on the degree of maturation of the system involved in ß-adrenergic signaling. All the existing data draw attention to the possible harmful consequences of the clinical use of ß-AR agonists during early phases of cardiac development. Late effects of the early disturbances of the cardiac muscle cannot be excluded.