The Effect of Chemical Sympathectomy on Catecholamine Release at Birth

Abstract

The precise source of circulating catecholamine (CA) at birth and their role in circulatory adaptation is unclear. In order to determine the contribution of increased postganglionic sympathetic nerve activity to the CA surge at birth, we induced complete sympathectomy in near term fetal lambs prior to delivery by giving 6-hydroxydopamine. Chronically catheterized fetal sheep received either 6-hydroxydopamine (n=5) or control infusion (n=6). Chemical sympathectomy was verified by tyramine infusion. Lambs were delivered at 142 ± 1 days of gestation and serial plasma CA, heart rate, blood pressure, cardiac output, blood gases, blood glucose, and free fatty acids, were measured before and for 4 h after delivery. Myocardial ß-adrenergic receptors and tissue CA concentration were determined following sacrifice. Baseline circulating norepinephrine (NE) values were lower in sympathectomized animals (183 ± 45 versus 373 ± 125 pg/ml, pversus 1305 ± 363 pg/ml respectively, pversus 35 ± 12 mg/dl). Plasma free fatty acid levels rose after cord cutting and were similar in both groups. Tissue NE content in the hearts of sympathectomized animals were less than 5% of control (mean 1.92 ± 0.5%), verifying the completeness of sympathectomy in this tissue. Myocardial ß-adrenergic receptors were 229 ± 21 versus 199 ± 26 fmol/mg protein in sympathectomized and control animals, respectively. These results suggest that the majority of circulating NE seen at birth arises from postganglionic sympathetic neurons rather than adrenal medullary secretion. The comparable hemodynamic and metabolic homeostasis of the two groups underscores the importance of increased circulating adrenal epinephrine at birth.