N.S. Assali

Pressor response to angiotonin in pregnant and nonpregnant women

Abstract 1.1. The pressor response to a standard intravenous dose of angiotonin (5 μg) was studied in pregnant, puerperal, and nonpregnant gynecologic women. 2.2. The postpartum pressor response to angiotonin was significantly higher than the prepartum response when tested in the same group of patients. 3.3. The pressor response of the nonpregnant gynecologic patients was similar to that of the postpartum subjects. This response was greater than that observed at any period of gestation. 4.4. These findings were discussed in relation to the rise in plasma angiotonase level during pregnancy, and in relation to the course of renal hypertension in pregnancy.

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.

Effects of Hyperbaric Oxygen on Uteroplacental and Fetal Circulation

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 PO2 rose to 1,300 mm Hg while umbilical vein blood PO2 rose to 300 mm Hg; umbilical arterial Po2 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.

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.

The dynamics of placental oxygen transfer: I. Effects of maternal hyperoxia in pregnant ewes and fetal lambs☆

Abstract The effects of hyperoxia at one atmosphere on placental oxygen transfer in the pregnant sheep have been studied. Fetal blood pO 2 does not increase proportionately to the maternal increase, but is effectively limited below values of 60 mm. Hg. Net umbilical oxygen transfer is reversibly reduced during maternal hyperoxia. The Krogh equation is inadequate to predict or explain these findings. The need for a model of placental gas diffusion employing terms dealing with blood flow rates, hemoglobin properties, concentrations, and geometric relationships is established.

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.

Regional blood flow and vascular resistance of the fetus in utero: Action of vasoactive drugs☆

T H E studies on the response of the fetus in utero to vasoactive drugs have centered around two main questions. The first question has been concerned with the changes in the fetal circulation when these agents are injected into the mother. Some author? have observed fetal bradycardia and hypotension after the administration of catecholamines to the mother and have attributed these to fetal asphyxia resulting from the uterine ischemia caused by these agents. Adams and associates,2 however, were unable to detect any circulatory alterations in the fetal lamb after the injection of single doses of catecholamines or angiotensin into the ewe. Neither were they able to note any alterations in the ewe when the same agents were injected into the fetus. These authors concluded that these vasoactive drugs either did not cross the placental bar-

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.