C.R. Brinkman

Development of neurohumoral control of fetal, neonatal, and adult cardiovascular functions

Neurohumoral control of fetal, neonatal, and adult cardiovascular functions have been reviewed. Resting fetal heart rate remains fairly constant but neonatal heart rate declines progressively, reaching adult levels within six to eight weeks; systemic arterial pressure rises while pulmonary pressure falls to adult levels within the first week after birth. Sympathetic and parasympathetic control of circulatory functions matures at different rates during fetal and neonatal development; the sympathetic system becomes active earlier in fetal life than does the parasympathetic system. After birth, the parasympathetic tone of the resting heart rate rises to adult levels while adrenergic tone decreases. Despite changing autonomic activities, resting heart rate is set at given levels through alterations in intrinsic control. In the fetus, peripheral circulation is under neurohumoral tone of increasing magnitude; after birth, neurohumoral tone declines progressively, reaching levels comparable to those of adult nonpregnant sheep. Fetal cardiovascular response to neurotransmitters increases with age because of maturation of the effector system. The pulmonary bed responds primarily to acetylcholine whereas the systemic circulation responds to norepinephrine. After birth, the neonatal cardiovascular system becomes four to five times more sensitive to the action of neurotransmitters mainly because of closure of vascular shunts and elimination of umbilicoplacental circulation. In the neonate and adult, the pulmonary vascular bed loses its reactivity to neurotransmitters.

Comparison of maternal and fetal cardiovascular functions in acute and chronic experiments in the sheep

Abstract Comparative studies have been made of various maternal and fetal circulatory functions and blood respiratory gases and pH obtained from pregnant sheep under acute experimental condition and from chronically instrumented animals. The maternal and fetal values observed in pregnant animals studied under pentobarbital anesthesia were compared to those observed in ewes studied under spinal anesthesia. In addition, the impact of various anesthetic agents on the behavior of maternal and fetal vasomotor tones and regional circulation was investigated. The data show that anesthetic agents affect cardiovascular functions in different ways. Some anesthetic agents abolish totally or partially maternal and fetal neural reflexes controlling circulatory functions; they also alter the vascular responses to vasoactive substances. Despite these alterations, the values for maternal and fetal circulatory functions in the acute anesthetized animal were not significantly different from those observed in the chronically instrumented, unanesthetized animal. In terms of research objectives, the data was used to discuss: (a) the criteria for defining the animals health condition; (b) knowledge of the effects of anesthesia on a given maternal and fetal function; (c) the place of the acute and the chronic experimental preparation; and (d) the care to be observed in comparing data with the published literature.

A comparison of the morbidity of midforceps and cesarean delivery

Neonatal and maternal outcome in 358 midforceps and 486 cesarean deliveries was compared by retrospective analysis. Neonatal outcome was evaluated on the basis of Apgar score, cord blood gas values, admission to the neonatal intensive care unit, and birth trauma. Maternal outcome was based on intraoperative and postoperative complications, blood loss, and hospital stay. There was no increase in significant short-term neonatal morbidity in the midforceps group, while maternal morbidity was higher in the cesarean delivery group. It is concluded that, in selected cases, midforceps delivery is safe for the neonate and mother.

Circulatory shock in pregnant sheep

Uteroplacental and fetal hemodynamics and oxygen transfer were studied in near-term pregnant sheep during progessively induced hemorrhagic shock and blood reinfusion. When the perfusing pressure fell to 50 or 60 mm. Hg, uteroplacental vascular resistance increased significantly and the blood flow fell more than the arterial pressure. These hemodynamic changes were probably related to the approaching of the critical closing pressure, although adrenergic stimulation cannot be ruled out. During maternal shock, uteroplacental oxygen transfer and fetal blood oxygen tension decreased markedly. Ductus arteriosus flow increased strikingly, most likely because of the fall in fetal blood Pot. This increase contributed to the maintenance of a normal fetal effective cardiac output during maternal shock. Despite an unaltered fetal effective cardiac output, umbilical blood flow decreased slightly and fetal oxygen consumption decreased significantly.

Effects of hydralazine on uteroplacental and fetal circulations

Abstract The effects on uteroplacental and fetal circulations of of hydralazine (Apresoline) when injected either into the mother or into the fetus or the neonate were investigated in near-term normotensive pregnant sheep. Intravenous doses of 0.2–0.5 mg. per kilogram given to the mother decreased arterial pressure and uterine blood flow to an equivalent degree; uterine vascular resistance did not change. Fetal cardiovascular functions were not appreciably affected but fetal blood PO 2 decreased significantly. When injected into the fetus, hydralazine reduced fetal arterial pressure only after 10 to 15 times the maternal dose was administered; no alterations occurred either in the fetal ascending aortic, ductus, and main pulmonary artery blood flows or in the fetal blood respiratory gases and pH. Similar effects were observed in the neonate. The implications of these findings in terms of: (a) maternal and fetal vascular reactivity to hydralazine, (b) effects on the fetus of vasodepressor drugs, and (c) the problem of uteroplacental autoregulation are discussed.

Effects of estrogens on systemic and regional circulations in normal and renal hypertensive sheep

Effects of estrogen administration on systemic and regional circulation were studied in normotensive and renal hypertensive, chronically instrumented nonpregnant and pregnant ewes. Arterial pressure, cardiac output, and uterine, renal, superior mesenteric, and iliac blood flows, as well as uterine oxygen transfer, were monitored before and after intravenous administration of Premarin or estradiol-17 beta. The results show that: (1) estrogen administration produces a marked decrease in uterine vascular resistance and increase in uterine blood flow and oxygen transfer, lasting for about 2 hours; (2) arterial pressure, cardiac output, and other regional blood flows were not affected by estrogens; (3) the magnitude of uterine vasodilatation produced by estrogens was greater in the hypertensive than in the normotensive animals; it was also greater in the nonpregnant than in the pregnant state; these findings indicate that the magnitude of uterine vasodilatation depends on the status of the uterine vascular resistance in the resting state; (4) blockade of the autonomic nervous system at various levels, as well as administration of a mild antihistaminic agent, failed to alter the magnitude of the estrogen-induced uterine vasodilatation. These results indicate that estrogens act directly on the uterine vascular bed and produce a redistribution of flows and resistances in the body; the precise sites of this redistribution are not as yet determined.

Nitroprusside-induced hemodynamic alterations in normotensive and hypertensive pregnant sheep☆☆☆

It has been suggested that sodium nitroprusside, a potent vasodilator, be used in the management of an acute hypertensive crisis during pregnancy. The present study was designed to evaluate the hemodynamic effects of this agent in the same group of chronically instrumented, unanesthetized pregnant sheep during two experimental periods: (a) normotension with intact kidneys, and (b) one-kidney hypertension. The results demonstrate that (1) nitroprusside is a potent vasodilator which lowers mean arterial pressure; (2) nitroprusside-induced tachycardia was greater in the hypertensive animal; (3) uterine blood flow decreased with the development of hypertension; (4) the hypertensive-induced reduction in uterine blood flow was increased by the infusion of nitroprusside.

Development of neuroeffector mechanisms in the carotid artery of the fetal lamb.

A survey has been made of mechanisms associated with vascular adrenergic neuroeffector transmission in the lamb fetuses between 53 days and term gestation. The common carotid artery was isolated for studies of enzymic activities, uptake of norepinephrine (NE) and reactivity to vasoactive agents. The extra-neuronal NE uptake, monoamine oxidase and catechol-O-methyltransferase activities were present in the carotid artery of the youngest fetuses. The contractile responses to NE and serotonin and neuronal NE uptake preceded the response to adrenergic nerve stimulation during fetal growth. These results suggest that the mechanisms for adrenergic transmitter inactivation, transmitter action on vascular smooth muscle cells, and neuronal transmitter delivery develop in that sequence.

Systemic and Pulmonary Hemodynamic Responses to Adrenergic and Cholinergic Agonists during Fetal Development

Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists were investigated in fetal lambs between 60 days and term gestation. The cardiovascular response to these agents increases with fetal age, and the increase is related to maturation of the effector system rather than the vascular receptors. The fetal pulmonary vascular bed and the ductus arteriosus are the primary components responding to acetylcholine; the systemic response is secondary to the occuring in the lung. Both fetal systemic and pulmonary vascular beds are under alpha-adrenergic control whereas the fetal heart is under beta-adrenergic control.

Circulatory shock in pregnant sheep: II. Effects of endotoxin on fetal and neonatal circulation

Abstract The effects of E. coli endotoxin upon fetal, immediate neonatal, and newborn (10 to 20 days) lamb circulation were studied. The fetus and immediate neonate tolerated doses 10 times greater than those proving lethal in adult pregnant sheep without exhibiting obvious signs of circulatory shock; arterial pressure, cardiac output, and vascular resistance were not significantly altered by these large doses. After 10 to 20 days of extrauterine life, the newborn lamb responded in a manner quite similar to the pregnant ewe; a biphasic acute response occurred after endotoxin injection followed by a slow decline in pressure and cardiac output until the termination of the experiment. We believe that the smaller response of the fetus and early neonate to endotoxin may be related not only to the presence of vascular shunts but also to a poorly developed adrenergic system.