Significant activation of the sympathoadrenal system (SAS) occurs during the transition from fetal to neonatal life. Increases in circulating catecholamines, derived predominantly from adrenal medullary secretion and also post-ganglionic sympathetic nerves, support major cardiovascular, pulmonary and metabolic adaptations to postnatal life. While activation of the sympathoadrenal system is vital to these alternation the duration of this dependence is unknown. The duration of elevated circulating catecholamines will be determined in newborn sheep. The effects of ablation of these responses through adrenalectomy will be determined in preterm sheep. Physiologic thresholds for the hemodynamic, metabolic and endocrine effects of circulating catecholamines in newborn and adult sheep will be compared with recent data from fetal animals. The contribution of individual organ systems to the catecholamine responses at birth and the physiologic significance of regional metabolism of catecholamines will be elucidated using regional organ kinetic studies. The pulmonary vascular bed normally metabolizes a large fraction of circulating vasoactive amines. The developmental basis for this phenomenon in vivo will be studied. Endocrine changes during fetal life, including antenatal increases in cortisol and thyroid hormones, may importantly condition the sympathoadrenal system responses at birth. These effects on the developing sympathoadrenal system will be studied. Intrauterine growth retardation and chronic hypoxia may alter development of sympathetic nerve function, adrenal catecholamine synthesis, release of catecholamines or adrenergic receptor maturation. Each of these components of the SAS will be studied in growth retarded fetal lambs or lambs subjected to chronic hypoxia. The clinical pharmacology of adrenergic agents in use in critically ill neonates will be studied with sensitive and specific hormone assays. It is believed these experiments will lead to important new strategies new strategies for the care of premature infants as well as the compromised term infant.
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