Development of the ovine fetal cardiovascular defense to hypoxemia towards full term

Abstract

. Development of the ovine fetal cardiovascular defense to hypoxemia towards full term. Am J Physiol Heart Circ Physiol 291: H3023-H3034, 2006. First published July 21, 2006 doi:10.1152/ajpheart.00504.2006.-We tested the hypothesis that fetal cardiovascular responses to hypoxemia change close to full term in relation to the prepartum increase in fetal basal cortisol and investigated, in vivo, the neural and endocrine mechanisms underlying these changes. Fetal heart rate and peripheral hemodynamic responses to 1 h of hypoxemia were studied in 25 chronically instrumented sheep within three narrow gestational age ranges: 125-130 (n ϭ 13), 135-140 (n ϭ 6), and Ͼ140 (n ϭ 6) days (full term ϳ145 days). Chemoreflex function and plasma concentrations of vasoconstrictor hormones were measured. Reductions in fetal arterial PO2 during hypoxemia were similar at all ages. At 125-130 days, hypoxemia elicited transient bradycardia, femoral vasoconstriction, and increases in plasma concentrations of catecholamines, neuropeptide Y (NPY), AVP, ACTH, and cortisol. Close to full term, in association with the prepartum increase in fetal basal cortisol, there was a developmental increase in the magnitude and persistence of fetal bradycardia and in the magnitude of the femoral constrictor response to hypoxemia. The mechanisms mediating these changes close to full term included increases in the gain of chemoreflex function and in the magnitudes of the fetal NPY and AVP responses to hypoxemia. Data combined irrespective of gestational age revealed significant correlations between fetal basal cortisol and fetal bradycardia, femoral resistance, chemoreflex function, and plasma AVP concentrations. The data show that the fetal cardiovascular defense to hypoxemia changes in pattern and magnitude just before full term because of alterations in the gain of the neural and endocrine mechanisms mediating them, in parallel with the prepartum increase in fetal basal cortisol.fetus; prepartum cortisol surge; glucocorticoid IN ALL MAMMALIAN SPECIES studied to date, fetal basal cortisol concentration increases immediately before full term (23). In the ovine fetus, this increase in plasma cortisol begins in the last 15 days of gestation, at ϳ130 days (full term ϳ145 days) (3, 43), and increases most dramatically within the last 5 days before delivery, between 140 and 145 days. The prepartum cortisol surge is known to be an important factor in the developmental maturation of fetal tissues and physiological systems in preparation for the transition to neonatal life (23). For example, the prepartum maturation of basal cardiovascular function in the fetus is influenced by cortisol. The developmental increase in ovine fetal mean arterial blood pressure (FBP) and fall in fetal heart rate (FHR) are prevented by fetal adrenalectomy and restored to normal by cortisol replacement (63). Similarly, the prepartum cortisol surge has been associated with developmental changes in the basal activity of many fetal endocrine vasoconstrictor mechanisms, such as the norad...

Hypotension in the chronically hypoxic chicken embryo is related to the β-adrenergic response of chorioallantoic and femoral arteries and not to bradycardia

“…1), yet hypotension remained. In the absence of a chemoreflex, cardiovascular function in the chicken embryo is mainly maintained through adrenergic pathways stimulated by catecholamines of adrenomedullary rather than sympathetic origin (11), which, in turn, could elevate heart rate as shown in the chronically hypoxic sheep fetus (14,27). Circulating norepinephrine levels are increased in E19 chickens (Fig.…”

“…In the late-gestation sheep fetus, acute hypoxia elicits a chemoreflex resulting in an increase in vagal activity, causing bradycardia and an increased sympathetic vascular tone causing systemic vasoconstriction (19). This reflex is instrumental in the redistribution of cardiac output (CO) to the heart, brain, and adrenals, while blood is diverted away from the liver and kidneys (14,32). The initial hypoxic bradycardia is transient, and HR returns to baseline values during a more prolonged hypoxic period, likely due to the increase of humoral factors, such as catecholamines or vasopressin (14,27).…”

The vulnerable developing brain

“…For instance, it is known that the fetal chemoreflex and endocrine response to hypoxia mature in the last third of gestation, in parallel with the prepartum surge in fetal plasma cortisol (13). Consequently, exposure of the preterm fetus to synthetic glucocorticoid matures the brain-sparing response to term levels (14).…”

Mild chronic hypoxemia modifies expression of brain stem angiotensin peptide receptors and reflex responses in fetal sheep

“…In fetal sheep, acute episodes of hypoxemia induce a redistribution of cardiac output to maintain blood flow and oxygen delivery to the heart and brain (14). This response is initiated by stimulation of peripheral chemoreceptors and maintained by endocrine mechanisms involving secretion of hormones such as catecholamines, neuropeptide Y, arginine vasopressin, and cortisol (11). During acute severe hypoxia, i.e., complete occlusion of the umbilical cord, fetuses respond with a fall in heart rate (FHR) and an increase in blood pressure.…”

“…During acute severe hypoxia, i.e., complete occlusion of the umbilical cord, fetuses respond with a fall in heart rate (FHR) and an increase in blood pressure. This acute FHR during hypoxia represents a key fetal adaptation, believed to help reduce myocardial work and oxygen requirements (11). This initial bradycardia, which is mediated by chemoreflex vagal pathways (5,17,23), occurs before the increase in blood pressure and is an indication of the severity of the hypoxic insult (5).…”