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

• Published in: Canadian journal of physiology and pharmacology 2018-07, Vol.96 (7), p.639-646
• Main Authors: Ostadal, Bohuslav, Parizek, Antonin, Ostadalova, Ivana, Kolar, Frantisek
• Format: Article
• Language: English
• Subjects: Adrenergic receptors; Cardiac muscle; Cardiotoxicity; Cardiovascular system; Catecholamines; Embryogenesis; Embryonic growth stage; Innervation; Myocardium; Ontogeny; Pharmacology; Physiology; Pregnancy
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2017-0774

Catecholamines are involved in the regulation of a wide variety of vital functions. The β-adrenergic receptor (β-AR) - adenylyl cyclase (AC) system has been identified early in embryogenesis before the heart has received adrenergic innervation. The structure of β-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 β-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 β-AR agonists induce malformations of the cardiovascular system; the type of change depends upon the time at which the β-AR agonist was administered during embryogenesis. During postnatal ontogeny the cardiotoxicity of β-AR agonists increased from birth to adulthood. It seems likely that despite interspecies differences, developmental changes in the cardiac sensitivity to β-AR agonists may exist in all mammals depending on the degree of maturation of the system involved in β-adrenergic signaling. All the existing data draw attention to the possible harmful consequences of the clinical use of β-AR agonists during early phases of cardiac development. Late effects of the early disturbances of the cardiac muscle cannot be excluded.