Fetal Cardiovascular and Catecholamine Responses to Hypoxemia after Chemical Sympathectomy

Abstract

SummaryChemical sympathectomy was performed in fetal lambs in utero by daily intravenous administration of 6-hydroxydopamine (6HD) until a total dose of 60-70 mgFg was reached. The completeness of adrenergic denervation was confirmed by the absence of any cardiovascular response to tyramine infusion. Baseline plasma catecholamine concentrations in normoxemic, sympathectomized fetuses were slightly higher than controls but the differences were not statistically significant. The concentration of norepinephrine (NE) was 313 + 73 pg/ml after 6HD administration compared with 259 + 25 pg/ml in control animals. Similarly, the concentration of epinephrine (E) was 39 + 15 pg/ ml (6HD) versus 21 f 4 pg/ml (control). These mildly elevated catecholamine levels were accompanied by a small but significant increase in resting blood pressure (BP) ( P < 0.05). Heart rate (HR), however, was no different from control. Hypoxemia induced a marked increase in plasma catecholamines in control animals (NE, 2416 f 419 pg/ml and E, 2017 2 749 pg/ml) along with hypertension and bradycardia. Sympathectomized fetuses maintained a profound NE response to hypoxemia (NE, 1550 f 261 pg/ml) but a significant reduction in peak E response was observed (E, 244 + 42 pg/ml, P c 0.05). HR and BP responses to hypoxemia were generally similar to control animals though there ameared to be a brief 1-3-min lag ~eriod between the nadir of the bradycardia and the peak of the BP response. We conclude that the generalized chemical sympathectomy after 6HD administration in the fetal lamb in utero is useful in evaluating the interaction of the autonomic nervous system and adrenal medullary function on the regulation of the fetal cardiovascular system. Abbreviations BP, blood pressure E, epinephrine 6HD, 6-hydroxydopamine HR, heart rate NE, norepinephrine NS, not significant Hypertension and bradycardia characterize the fetal cardiovascular response to hypoxemia and are mediated by increases in sympathetic and parasympathetic tone (2,3,14,16,23). The increased level of sympathetic tone appears to be the result of synergism between elevated adrenergic neuronal activity and circulating catecholamines (4, 1 3, 15). Previous investigations in normoxemic fetal lambs have shown that NE is the predominant circulating catecholamine whereas E is present in relatively low concentrations (4,5,13,15). Under hypoxemic conditions, NE levels rise 8-10-fold whereas plasma E increases approximately 50-fold (8, 15). Additionally, increased activity in the sympathetic nerves supplying systemic arteriolar resistance vessels may augment further the degree of catecholamine-mediated vasoconstriction. Nevertheless, the relative contributions of both adrenergic neuronal tone and humoral catecholamines to the overall compensatory sympathetic response of the hypoxic fetus remains unclear.Sympathectomy has often been used to study the activity of the sympathetic nervous system. Comline and Silver (4, 5) have shown that splanchnic denervation of the fetal adrenal glands results in decrease i...

The Effect of Chemical Sympathectomy on Catecholamine Release at Birth

“…60HDA is not reported to affect adrenal medullary CA content or secretion (13,23,24,26). This is consistent with our observation that E in both groups increased markedly after cord cutting, reaching concentrations 5-to 7-fold higher than basal levels.…”

“…There may have been some direct effect of 60HDA on adrenal function although this is said not to occur. Lewis et al (13) performed chemical sympathectomy with 60HDA in chronically catheterized fetal sheep and then subjected them to hypoxia. NE responses were only reduced marginally in the denervated animals but the E responses were markedly decreased.…”

“…DISCUSSION 60HDA is a synthetic CA which causes acute depletion of sympathetic neuronal stores of NE followed by histologic, electronmicrographic, and biochemical evidence of prolonged destruction of postganglionic sympathetic neurons. Its use in experimental models has been extensive (12) and recent studies have been conducted in fetal and newborn sheep to investigate the role of the sympathetic nervous system in responses to hypoxia and circulatory control (13,23,24). In order to investigate the origin of increased circulating CA at birth in newborn lambs we performed chemical sympathectomy with 60HDA on chronically catheterized fetal sheep.…”

Cardiovascular and Catecholamine Responses to Successive Episodes of Hypoxemia in the Fetus

“…3), and were similar to previously reported levels from our laboratory [8,13]. Following the initial episode of cord com pression-induced hypoxemia, plasma NE and E rose to 7,190 ± 4,190 and 2,217 ± 1,576 pg/ml, respectively.…”

The role of the neural sympathetic and parasympathetic systems in diurnal and sleep state-related cardiovascular rhythms in the late-gestation ovine fetus

“…Peripheral sympathectomy achieved by 6-OHDA leads to loss of sympathetic nerve terminals, and thus of peripheral norepinephrine release (18,22). We found no effect of sympathectomy on norepinephrine levels, which indicates that norepinephrine was still being released from other sources, such as the adrenal gland.…”