Significant physiological adaptations are required for successful newborn transition to life outside the womb. These include major cardiovascular, pulmonary and metabolic alterations. Ample evidence exists to suggest that neurosympathetic system activation is vital to these adaptive changes. We have developed the ability to support a premature lamb in the extrauterine environment in much the same fashion as we would a premature infant. This model and highly sensitive methods to measure plasma and tissue catecholamine levels make it possible to further explore the role of catecholamines, the hormone-neurotransmitters released by the neurosympathetic system, in the circulatory and metabolic alterations occurrring in the newborn period. We will examine the magnitude of catecholamine release at the time of birth at several developmental ages, measure catecholamine production rates and clearance rates, and measure the thresholds for circulatory and metabolic effects. Preliminary evidence suggests that part of the disproportionately higher newborn mortality in male infants is due to delayed neurosympathetic maturation relative to female infants. We plan to examine sex differences in catecholamine physiology to support or refute this hypothesis.
The specific aims of the present project will provide valuable insights into the mechanisms of newborn adaptation. A better understanding of these mechanisms will allow development of strategies for augmentation of neurosympathetic control or pharmacologic manipulation of the neurosympathetic system which will improve survival of the premature infant as well as the compromised term infant.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Los Angeles County Harbor-UCLA Medical Center
United States
Zip Code
Stein, H M; Martinez, A; Oyama, K et al. (1995) Effect of corticosteroids on free and sulfoconjugated catecholamines at birth in premature newborn sheep. Am J Physiol 268:E28-32
Stein, H M; Martinez, A; Blount, L et al. (1994) The effects of corticosteroids and thyrotropin-releasing hormone on newborn adaptation and sympathoadrenal mechanisms in preterm sheep. Am J Obstet Gynecol 171:17-24
Berg, R A; Donnerstein, R L; Padbury, J F (1993) Dobutamine infusions in stable, critically ill children: pharmacokinetics and hemodynamic actions. Crit Care Med 21:678-86
Stein, H; Oyama, K; Martinez, A et al. (1993) Plasma epinephrine appearance and clearance rates in fetal and newborn sheep. Am J Physiol 265:R756-60
Stein, H M; Oyama, K; Martinez, A et al. (1993) Effects of corticosteroids in preterm sheep on adaptation and sympathoadrenal mechanisms at birth. Am J Physiol 264:E763-9
Berg, R A; Padbury, J F; Donnerstein, R L et al. (1993) Dobutamine pharmacokinetics and pharmacodynamics in normal children and adolescents. J Pharmacol Exp Ther 265:1232-8
Oyama, K; Padbury, J; Chappell, B et al. (1992) Single umbilical artery ligation-induced fetal growth retardation: effect on postnatal adaptation. Am J Physiol 263:E575-83
Stein, H M; Oyama, K; Sapien, R et al. (1992) Prolonged beta-agonist infusion does not induce desensitization or down-regulation of beta-adrenergic receptors in newborn sheep. Pediatr Res 31:462-7
Oyama, K; Padbury, J; Martinez, A et al. (1992) Effects of fetal growth retardation on the development of central and peripheral catecholaminergic pathways in the sheep. J Dev Physiol 18:217-22
Martinez, A M; Padbury, J F; Thio, S (1992) Dobutamine pharmacokinetics and cardiovascular responses in critically ill neonates. Pediatrics 89:47-51

Showing the most recent 10 out of 38 publications