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Development of parasympathetic and sympathetic reflexes controlling heart rate, vascular pressures, and blood flows was investigated in fetal lambs weighing 300-5,800 g (65-165 days' gestation). Cardiovascular responses to veratridine injections, atrial stretching, bilateral cervical vagotomy, and cholinergic blockade with atropine were used to test parasympathetic activities. Responses to propranolol and phenoxybenzamine were used to test beta- and alpha-adrenergic activities. Autonomic ganglionic blockade and stimulation provided additional information on both cholinergic and adrenergic systems. Fetal responses to various tests were compared to those of the mother. Results show: a) little parasympathetic tone on resting heart rate and other circulatory functions exists prior to fetal maturity; b) despite the feeble resting tone, the parasympathetic system is capable of exerting significant control when stimulated in both premature and mature fetuses, the capability increases as fetus approaches term; c) alpha- and beta-adrenergic tone in control of resting heart rate and peripheral circulation exists in early fetal life and increases as the fetus reaches maturity, and both adrenergic receptors respond strongly to stimuli in immature, premature, and mature fetuses; d) in immature fetuses, veratridine does not elicit a vagally mediated reflex; instead, it produces a centrally mediated alpha- and beta-adrenergic stimulation; e) the fetal cardiovascular response to any given test is dampened by the existence of the various vascular shunts, the umbilicoplacental circulation and, possibly, by incomplete maturation of vasomotor tone.

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SUMMARY We studied the autonomic control of resting heart rate and of systemic and pulmonary vascular blood pressures (BP) in chronically instrumented neonatal lambs 1-8 weeks of age. The maximum response to ganglionic blockade and sympathetic and parasympathetic antagonists was taken as an index of the magnitude of the total neural, adrenergic, and cholinergic tones. The reactivity of the circulatory parameters to adrenergic and cholinergic agonists also was investigated. All findings were compared with those in adult nonpregnant sheep studied concomitantly and with data previously obtained from term fetal lambs. The results of our studies show: (1) resting heart rate declines spontaneously throughout the 8 weeks of neonatal life approaching that of adult sheep; (2) the progressive bradycardia is not related to changes in the parasympathetic or sympathetic tone; (3) resting systemic BP is under strong neurohumoral control during the first two to three weeks of neonatal life; the control decreases progressively, becoming similar to that of adult sheep; (4) resting pulmonary artery pressure of neonatal and adult sheep has no neurohumoral control; (5) the systemic BP response of the neonate to autonomic agonists is greater than that of the term fetus and is similar to that of the adult; (6) in neonatal and adult sheep, compared to the term fetus, the pressor response to norepinephrine is accompanied by a baroreceptormediated bradycardia, and acetylcholine-induced systemic hypotension is accompanied by a "paradoxical" tachycardia mediated through /3-adrenergic stimulation; (7) in contrast to our finding for the fetus, the pulmonary vascular pressure of neonatal and adult sheep is unresponsive to autonomic agonists.PREVIOUS studies on fetal lambs between 60 days and term gestation (fetal weight, 300-5,00,0 g) have shown that (1) the sympathetic control of the cardiovascular functions begins earlier during fetal development than the parasympathetic control; (2) the influence of both systems on the fetal circulation increases with fetal growth until term; and (3) the fetal cardiovascular response to autonomic agonists increases during intrauterine development mainly because of maturation of the effector system. 1 ' 2The present report deals with data that compare the changes in the neurohumoral control of the heart rate, systemic arterial pressure, and pulmonary vascular pressure of the neonatal lamb (3-60 days of age) with changes in the adult nonpregnant sheep. MethodsNear-term ewes of mixed breed with well dated gestation were allowed to deliver spontaneously in our animal facilities; hence, the exact age of each lamb was known. The lambs were housed with their mothers so that normal lactation could be accomplished until they were able to eat the same alfalfa diet given to the ewes and drink on their own during the period of observation. Each lamb was allowed a 2-to 3-day period of neonatal adjustment before it was subjected to surgery. Chronic instrumentation of the lamb or the adult sheep was accomplished under a...

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Changes in resting cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR) during neonatal growth were studied in chronically instrumented lambs from the 1st to 5th wk of age; adult nonpregnant sheep values measured simultaneously were used as standard reference. Neonatal responses to autonomic agonists and antagonists were also investigated. Total CO increased linearly with neonatal growth, but decreased strikingly when expressed per weight unit; at 5 wk of age, CO/kg was still significantly higher than the adult value. SV also increased with neonatal growth but did not change when related to body weight; at 5 wk of age, SV/kg values were still higher than those of adult sheep. SVR changed reciprocally to CO. The decrease in CO/kg during neonatal growth paralleled the progressive decline in heart rate (HR). Beta receptor stimulation increased neonatal CO markedly and the increment was the same from the first through the fifth neonatal week. Beta blockade had insignificant effects, but cholinergic blockade produced moderate CO increases.

The effects of hyperbaric oxygen (at 3 atmospheres absolute) on uteroplacental and fetal circulations were studied in pregnant ewes near term. The ewe was given spinal anesthesia, the fetus was marsupialized to the abdominal walls to protect the umbilical circulation, and the fetal head was covered with a saline-filled glove to prevent breathing. During hyperbaric oxygenation, maternal arterial blood Po 2 rose to 1,300 mm Hg while umbilical vein blood Poo rose to 300 mm Hg; umbilical arterial Po 2 rose to only 50 mm Hg. Maternal and fetal arterial pressures did not change significantly, but uteroplacental and umbilical flows decreased slightly. Ductus arteriosus blood flows decreased strikingly when the oxygen tension of the pulmonary blood rose; net pulmonary blood flow increased markedly because of a decrease in pulmonary vascular resistance produced by oxygen. Ascending aortic flow increased, but effective fetal cardiac output (aortic plus ductus arteriosus flows) decreased. These studies indicate that the fetal pulmonary vascular bed is sensitive to oxygen in that it undergoes vasodilatation when the oxygen tension of the blood passing through it rises; the ductus arteriosus responds to the same stimulus by constricting. Hyperbaric oxygenation seems to establish a circulatory pattern in the fetus similar to that of the early neonatal period.From the

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