Fetal cardiovascular and catecholamine responses to hypoxemia after chemical sympathectomy

Chemical sympathectomy was performed in fetal lambs in utero by daily intravenous administration of 6-hydroxydopamine (6HD) until a total dose of 60-70 mg/kg was reached. The completeness of adrenergic denervation was confirmed by the absence of any cardiovascular response to tryamine 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 +/- 4 pg/ml (control). These mildly elevated catecholamine levels were accompanied by a small but significant increase in resting blood pressure (BP) (P less than 0.05). Heart rate (HR), however, was no different from control. Hypoxemia induced a marked increase in plasma catecholamines in control animals (NE, 2416 +/- 419 pg/ml and E, 2017 +/- 749 pg/ml) along with hypertension and bradycardia. Sympathectomized fetuses maintained a profound NE response to hypoxemia (NE, 1550 +/- 261 pg/ml) but a significant reduction in peak E response was observed (E, 244 +/- 42 pg/ml, P less than 0.05). HR and BP responses to hypoxemia were generally similar to control animals though there appeared to be a brief 1-3 min lag period 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.