Cardiovascular Responses to Autonomic Blockade in Hypoxemic Fetal Lambs

Abstract

The cardiovascular responses of 11 fetal lambs in utero to hypoxemia were evaluated before and after autonomic blockade. Hypoxemia was produced by lowering the maternally inspired oxygen or by progressive constriction of the umbilical cord by a cuff occluder. The animals were studied serially from 112 days’ gestation to term. Fetal carotid arterial pO₂ fell from 24 to 12 torr and was accompanied by a 35% decline in heart rate and 32% rise in blood pressure. Parasympathetic blockade with atropine produced a 114% increase in heart rate in the hypoxemic fetuses compared to 26% in the normoxemic controls. Pretreatment with atropine prevented the hypoxemia-induced bradycardia without altering the hypertensive response. α-Adrenergic blockade resulted in a 22% decrease in blood pressure in the hypoxemic group, three times greater than the controls. Pre-hypoxemia α-blockade prevented the hypertension without affecting the fall in fetal heart rate. It is concluded that fetal bradycardia in response to hypoxemia is due to a direct increase in parasympathetic activity rather than secondary to a hypertension-induced baroreflex. The α-mediated increase in systemic vascular resistance and blood pressure may be a compensatory mechanism to maintain placental blood flow despite the decline in combined ventricular output.

Fetal Cardiovascular and Catecholamine Responses to Hypoxemia after Chemical Sympathectomy

“…The vagally mediated decline in HR occurs promptly with the onset of significant hypoxemia and, as we have demonstrated previously, is not merely the result of a baroreflex phenomenon (14). The rise in BP, however, appears to be somewhat more gradual in the chemically sympathectomized fetus.…”

“…Furthermore, the inter-relationship of adrenergic neuronal and humoral elements also occurs within the adrenal gland itself because sympathetic innervation of the adrenal medulla appears to be essential for the proper discharge of E into the circulation during hypoxia. Before the development of the sympathetic nerve supply to the adrenal gland during the final quarter of gestation, the hypertensive response of the fetus to hypoxia appears to be regulated adequately by the interaction of the sympathetic nervous system and adrenal medullary NE release (14,15).…”

“…Ten fetal lambs with time-dated gestations were operated between 105-1 15 d (0.70-0.77 gestation) as previously described (14)(15)(16). Briefly, the ewes were sedated with acepromazine and low spinal anesthesia was administered.…”

“…Fetal arterial POz was lowered to 10-12 torr by gradual constriction of the umbilical cord over 15-30 min during which time the ewe breathed room air (14,15). Arterial blood specimens for catecholamine analysis were obtained during a pre-hypoxia control period and during maximal hypoxia.…”

“…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).…”