Effects of hypoxia-ischemia and inotropes on expression of cardiac adrenoceptors in the preterm fetal sheep
| Autor: | Nadia Hale, Flora Y. Wong, Nadine Brew, Teresa Vu, Dana S. Hutchinson, Jon Merlin, David W. Walker |
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| Rok vydání: | 2018 |
| Předmět: |
Inotrope
medicine.medical_specialty Cardiotonic Agents Adrenergic receptor Physiology Dopamine Adrenergic Hypoxia ischemia 03 medical and health sciences 0302 clinical medicine Ischemia Dobutamine 030225 pediatrics Physiology (medical) Internal medicine medicine Animals Hypoxia Fetus Sheep business.industry Myocardium Heart Hypoxia (medical) Receptors Adrenergic Endocrinology Animals Newborn Models Animal medicine.symptom business Infant Premature 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Applied Physiology. 125:1368-1377 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.00472.2018 |
| Popis: | Preterm infants frequently suffer cardiovascular compromise, with hypotension and/or low systemic blood flow, leading to tissue hypoxia-ischemia (HI). Many preterm infants respond inadequately to inotropic treatments using adrenergic agonists such as dobutamine (DB) or dopamine (DA). This may be because of altered cardiac adrenoceptor expression because of tissue HI or prolonged exposure to adrenergic agonists. We assessed the effects of severe HI with and without DB/DA treatment on cardiac adrenoceptor expression in preterm fetal sheep. Fetal sheep (93–95 days) exposed to sham surgery or severe HI induced by umbilical cord occlusion received intravenous DB or saline for 74 h (HI + DB, HI, Sham + DB, Sham). The HI groups were also compared with fetal sheep exposed to HI and DA. Fetal hearts were collected to determine β-adrenoceptor numbers using [125I]-cyanopindolol binding and mRNA expression of β1-, β2-, α1A-, α2A-, or α2B-adrenoceptors. The HI group had increased β-adrenoceptor numbers compared with all other groups in all four heart chambers ( P < 0.05). This increase in β-adrenoceptor numbers in the HI group was significantly reduced by DB infusion in all four heart chambers, but DA infusion in the HI group only reduced β-adrenoceptor numbers in the left atria and ventricle. DB alone did not affect β-adrenoceptor numbers in the sham animals. Changes in β1-adrenoceptor mRNA levels trended to parallel the binding results. We conclude that HI upregulates preterm fetal cardiac β-adrenoceptors, but prolonged exposure to adrenergic agonists downregulates adrenoceptors in the preterm heart exposed to HI and may underpin the frequent failure of inotropic therapy in preterm infants. NEW & NOTEWORTHY This is the first study, to our knowledge, on the effects of hypoxia-ischemia and adrenergic agonists on adrenoceptors in the preterm heart. In fetal sheep, we demonstrate that hypoxia-ischemia increases cardiac β-adrenoceptor numbers. However, exposure to both hypoxia-ischemia and adrenergic agonists (dobutamine or dopamine) reduces the increase in β-adrenoceptor numbers, which may underpin the inadequate response in human preterm infants to inotropic therapy using adrenergic agonists. Dobutamine alone does not affect the cardiac adrenoceptors in the sham animals. |
| Databáze: | OpenAIRE |
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