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Biomedical subjects

L D Longo

Publications and source records attributed to L D Longo.

At least 109 records · Page 6Linked to original sources

Fate of labeled albumin and erythrocytes following injection into amniotic cavity of sheep.

We have previously described a method to measure the amniotic fluid (AF) volume and fetal swallowing rate in near-term sheep by use of 125I-labeled albumin (RISA) and 51Cr-labeled red blood cells (51Cr-RBC). However, when we measured these volumes on consecutive days, reentry of the radionuclides into the amniotic cavity from fetal urine affected the calculated values of AF volume and swallowing rates. In an attempt to clarify the recirculation problem, we injected RISA and Cr-RBC daily for 9 days into the AF of five chronically catheterized pregnant sheep (124 days gestation on the 1st experimental day). We calculated AF volume and fetal swallowing rate, comparing those values to the values corrected for fetal urine isotopic counts. The mean AF volume and fetal swallowing rate measured by RISA were 808 +/- 48 ml (mean +/- SE) and 559 +/- 29 ml/day, respectively. These values were only slightly different from the corrected volumes, 808 +/- 48 ml and 561 +/- 29 ml/day, respectively, because fetal urine 125I activity reached only 4.8% of AF activity even on the 9th day. In contrast, 51Cr-activity in fetal urine on the 9th day showed 47% of the activity of AF. The mean uncorrected AF volume (785 +/- 44 ml) and swallowing rate (561 +/- 31 ml/day) measured by Cr-RBC were different from the corrected values (790 ml and 570 ml/day, respectively). After the 4th day these differences were particularly conspicuous.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnion↗

Catecholamine secretion from the adrenal medulla of the fetus, regulation by hormones.

In the ovine fetus, the adrenal medulla activity secretes catecholamines into the circulation under normal and stress conditions. Little is known regarding the endocrine regulation of adrenal medullary catecholamine secretion in the fetus. The present study was undertaken to investigate the direct effects of the hormones prolactin, angiotensin II and cortisol on catecholamine release from fetal adrenal medulla, and to determine whether the effect of the hormones change during development into adulthood. Adrenal medulla from fetal, newborn and adult pregnant sheep was collected, dispersed into single cells and plated. Following preincubation, the cells were treated with ovine prolactin or angiotensin II at 8, 40 and 200 micrograms/ml; or cortisol at 10(-8), 10(-7) and 10(-6)M for 24 h. Catecholamine release into the medium were measured at 3, 6, 12 and 24 h. Ovine prolactin at 8 to 200 micrograms/ml significantly stimulated the release of total catecholamines after 12 h of incubation. The effect of prolactin was dose-dependent such that the magnitude of the response increased and the response time shortened with increasing concentrations of prolactin. In addition, the release of all three catecholamines--dopamine, norepinephrine and epinephrine--was significantly elevated. In newborn cells, only the highest concentration of 200 micrograms/ml ovine prolactin stimulated total catecholamine release at 6 h and 12 h, with significant increases of the three catecholamines at 12 h. In maternal cells, stimulation of catecholamine release was observed also with the highest concentration of prolactin tested (200 micrograms/ml) and after 12 h of incubation, when only the release of epinephrine was significantly enhanced by 324%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

A comparison of sheep and human fetal oxygen delivery systems with use of a mathematical model.

Human fetal cardiac output measured with ultrasound is only about 60% of that found in the sheep. We modified a previously developed mathematical model of the fetal circulation and oxygen delivery in sheep for the human in order to study several differences. The model predicts that a human fetus can maintain its oxygen delivery with a relatively low cardiac output because of its relatively high fetal hemoglobin concentration, as compared with that of the sheep fetus. Thus an inverse relationship between fetal hemoglobin concentration and fetal cardiac output is suggested. This relationship may be mediated by the influence of red blood cell concentration on blood viscosity. Furthermore, it indicates that fetal anemia should be detectable by ultrasound measurements of increased cardiac output and/or umbilical blood flow. Dynamic responses of the model suggest that the mechanism of late and variable decelerations in the fetal heart rate pattern is mediated via a fall in arterial oxygen tension.

Animals↗

Vasopressin dose-response effects on fetal vascular pressures, heart rate, and blood volume.

To determine the effects of circulating arginine vasopressin (AVP) on fetal arterial pressure, venous pressure, heart rate, and blood volume, we infused graded amounts of AVP into chronically catheterized fetal sheep at 122-136 days gestation (term 145-150 days). Plasma AVP concentrations increased by 6.5 +/- 3.9 (SE), 13.0 +/- 2.4, 55 +/- 11.7, and 144 +/- 42 pg/ml with infusion rates of 1, 3.3, 10, and 33 ng/min, respectively. Fetal arterial pressure rose 0, 7.2 +/- 1.0, 9.1 +/- 2.5, 11.4 +/- 2.9, and 12.1 +/- 2.4 mmHg while heart rate decreased 0, 24 +/- 5, 36 +/- 10, 59 +/- 9, and 62 +/- 9 beats/min during AVP infusions of 0.5, 3.3, 10, 33, and 700 ng/min, respectively. Fetal venous pressure was unchanged except that it increased 2.4 +/- 0.5 and 4.8 +/- 1.5 mmHg at infusion rates of 33 and 700 ng/min, respectively. Fetal blood volume remained unchanged except for a 7.2 +/- 3.4% decrease with 700 ng/min. After blockade of the fetal autonomic nervous system, the arterial pressure increase was twice and the heart rate decrease was one-third of those observed in autonomically intact fetuses with comparable AVP infusion rates. Thus these fetal cardiovascular variables showed differential sensitivity to increases in circulating AVP concentrations, suggesting that physiological variations in endogenous AVP may have short-term effects on fetal arterial pressure and heart rate, but probably not on venous pressure or blood volume.

Animals↗

Amniotic fluid volume and fetal swallowing rate in sheep.

To investigate amniotic fluid (AF) dynamics and volume regulatory mechanisms, we measured the concentration of radioiodinated (125I) serum albumin (RISA), 51Cr-labeled red blood cells (Cr-RBC), and 103Ru-labeled microspheres after injection into the amniotic cavity and determined AF volume and fetal swallowing rate in 22 singleton pregnant sheep. Under normal conditions 2-3 h were required for complete mixing of RISA and Cr-RBC within AF; however, when the fetus was dead only 3-5 h were required. AF volume of 17 sheep on the 5th postoperative day averaged 975 +/- 128 ml by RISA and 986 +/- 130 ml by Cr-RBC. AF volume determined with RISA and Cr-RBC correlated well. In contrast, AF volume measurement with microspheres produced erratic results. The disappearance rate of the labels in 17 ewes on the 5th postoperative day averaged 4.9 +/- 0.7%/h for RISA and 5.5 +/- 0.7 for Cr-RBC, and the calculated rates of fetal swallowing were 935 +/- 78 ml/day by RISA and 1,085 +/- 102 by Cr-RBC. In dead fetuses the disappearance rates were almost zero, suggesting that the labels disappear mainly by swallowing. Absolute volume swallowed and swallowed volume per fetal weight correlated with gestational age. AF volume correlated with fetal weight. Radiolabeled albumin or red blood cells may be used to simultaneously measure amniotic fluid volume and the rate of fetal swallowing. Furthermore it appears that fetal swallowing increases with gestational age.

Amniotic Fluid↗

Mathematical model of fetal circulation and oxygen delivery.

To better understand the fetal circulation and its regulation we constructed a dynamic model of fetal circulation as a transport system. The fetal vascular system is divided into 16 compartments which incorporate the peculiarities of the fetal circulation that produce a difference in oxygen concentration in blood supplying the upper and lower body. Recently published data is used to provide a firm experimental base for the model. The model is used to examine how the results on parts of the fetal cardiovascular system and fetal oxygen consumption are compatible and form a coherent description. We also studied the effects of disturbances from the normal steady state produced by changes in patterns of and resistances to blood flow. A maternal placental blood flow of less than 200 ml X min-1 X kg fetal wt-1 produces a steady-state value of oxygen tension in the fetal ascending aorta of less than 17 mmHg, which is incompatible with normal oxygen delivery. A minimal value of umbilical flow providing an adequate oxygen supply to the fetal body is 87 ml X min-1 X kg fetal wt-1. Due to the geometry of the fetal circulation, the highest normal oxygen tension in the fetal ascending aorta is approximately 25 mmHg, only 8 mmHg above the lowest normal tension of 17 mmHg. Dynamic studies using the model demonstrate differences in response of fetal arterial oxygen tension to temporal cord occlusion and temporal decrease in maternal placental flow.

Blood Circulation↗

Maternal and fetal responses to exercise during pregnancy.

Exercise has numerous effects on the pregnant woman, the developing fetus, and the placenta. In turn, pregnancy affects the ability to perform physical activity. During pregnancy, increased metabolism at rest results almost exclusively from the gestational increase in mass. Because of this increase, a higher cardiorespiratory effort is required to perform a given amount of external work. One would expect the result to be some training effect, unless a more sedentary lifestyle is adopted. The possibility that maximal O2 consumption may increase during pregnancy has not been studied extensively, yet it is a most important variable that puts other changes in perspective. The sedentary lifestyle commonly adopted in late pregnancy in most western societies may reflect a cultural rather than a physiological phenomenon. In contrast to the physiological alterations in the mother and despite the reductions in uterine blood flow during maternal exercise, physiological changes in the fetus are small. Relatively minor changes occur in the blood concentrations of O2 and substrates during prolonged exhaustive exercise. In addition, despite a temperature increase of 1 to 2 degrees C, there is little evidence for significant alteration in fetal metabolism, cardiovascular hemodynamics, or blood catecholamine concentrations. These observations suggest that acute exercise normally does not represent a major stress for the fetus. Of course, most of the information concerning the fetus is derived from studies in experimental animals, particularly in sheep. In humans the upright position and increased uterine contractibility may affect the fetal responses differently. Virtually nothing is known about the physiological effects of exercise training on the fetus. The most likely effect may be a relatively small reduction in birth weight in some species, but this needs further investigation. Further studies are also needed for a more complete understanding of the mechanisms involved in the remarkably effective mechanisms that account for the relative homeostasis of the fetus during maternal exercise.

Animals↗

The relation of maternal blood volume to plasma renin activity in the pregnant rabbit.

Blood volume, estradiol 17 beta and estrone concentrations, and plasma renin activity were determined weekly in 26 chronically catheterized nonanesthetized rabbits during pregnancy and after delivery. We determined blood volume by 99technetium, and plasma volume by the microhaematocrit method. The values for whole blood volume were 52.7 (+/- 2.3) and 63 (+/- 2.2) ml X kg-1 for nonpregnant and pregnant animals, respectively. During the course of gestation plasma renin activity increased about 300%, but estradiol 17 beta and estrone concentrations did not change significantly. The increase in whole blood and plasma volumes during pregnancy correlated highly with the increase in plasma renin activity, r = 0.53 and 0.59, respectively.

Animals↗

Temperature effects on oxygen affinity of human fetal blood.

In an effort to understand the effects of temperature changes on fetal oxygenation, the temperature effects were measured on oxygen affinity of whole blood from term human fetuses. The blood obtained was tonometered at delivery in two flasks gassed with 95% N2 (+ 5% CO2 or 20.9% + 5% CO2, and mixed aliquots from each flask in different proportions to obtain samples for analysis of PO2 and percent saturation. The oxyhaemoglobin dissociation curve was constructed and P50 determined at two or three different temperatures for each batch of blood. As temperature increased from 30 to 41 degrees C, human fetal blood bound O2 less avidly, the temperature coefficient for changes in P50 being 0.0255 per degree C. This temperature effect was similar to that in adult blood, although at any temperature O2 affinity of fetal blood was greater than that of the adult. Placental oxygen exchange could be significantly affected by changes in temperature such as occur during hypo- or hyperthermia, as with maternal exercise.

Female↗

The interactions of exercise and pregnancy: a review.

Increasing numbers of women engage in relatively strenuous exercise during pregnancy. The interaction of the increased metabolic demands of physical activity with those of pregnancy is poorly understood. We review what is known and what is not known of the extent to which pregnancy affects a woman's ability to perform strenuous activity and the degree to which exercise affects the pregnant woman, the fetus, and the infant.

Body Temperature↗

Brainstem auditory evoked responses in the newborn lamb. Studies during postnatal development and acute hypoxia.

Brainstem auditory evoked responses (BAER) have been studied in several species and have provided a neurophysiologic 'window' into brainstem function. We have pursued further studies in the newborn lamb and adult sheep. BAER amplitude increased as the stimulus intensity increased from 45 to 95 dB and as the click frequency decreased from 88.8 to 22.2 Hz. BAER latency increased as both the stimulus intensity decreased and the click frequency increased. Developmental studies were performed between the 2nd and 35th day of life in the newborn lamb. No significant change in either latency, amplitude, or wave morphology was noted in contrast to other species where developmental changes are prominent. This was due to both the prenatal maturation of the lamb's brain and to the relatively short interval of the postnatal studies. We also studied the effect of prolonged severe hypoxia and acidosis on the BAER in the newborn lamb and found no significant change in either the amplitude or latency of the response.

Acidosis↗

Regional cerebral blood flow: studies in the fetal lamb during hypoxia, hypercapnia, acidosis, and hypotension.

In order to determine the relative roles of O2 tension and content, CO2 tension, hydrogen ion concentration, arterial blood pressure, and cardiac output in the regulation of fetal cerebral blood flow (CBF), we used radioactively labeled microspheres to measure flow to 20 major brain regions in 24 chronically catheterized fetal lambs. We continually monitored fetal heart rate and blood pressure, and periodically measured arterial PO2, PCO2, pH, and hematocrit. In addition to CBF measurements during control periods, we measured CBF during: 1) hypoxia (O2 content less than 6 ml X dl-1; O2 tension less than 15 torr) induced by having the ewe breathe a gas mixture with low O2 concentration, 2) hypercapnia (PCO2 greater than 50 torr) induced by increasing the maternal inspired CO2, 3) acidosis and alkalosis (7.60 greater than pH greater than 6.60) induced by infusing lactic acid or bicarbonate into the fetus, and 4) hypotension (blood pressure less than 35 mm Hg) and hypertension (blood pressure greater than 55 mm Hg) induced by rapidly phlebotomizing or transfusing the fetus. We used multiple regression analysis and analysis of covariance to examine the dependence of total cerebral blood flow on arterial O2 tension and content, CO2 tension, pH, blood pressure, and cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗

Acute embolization of the uteroplacental circulation: uterine blood flow and placental CO diffusing capacity.

In an effort to determine to what extent the fetal sequalae following repeated embolization result from decreased area of placental exchange or from decreased uterine blood flow, we injected microspheres into the uterine circulation of the pregnant ewe. We measured total UBF continuously and sampled fetal blood gases in 6 chronically instrumented ewes following repeated injections of 1 to 2 million 25 mu microspheres into the common internal iliac artery at 30 min intervals. Embolization resulted in an immediate 25 to 30% drop in uterine flow, with partial recovery to about 85% of its control value within 30 min after injection. A linear relation existed between uterine blood flow and fetal O2 tension. A slightly accelerated decrease in O2 content with a more rapid increase in CO2 tension and [H+] was seen when uterine flow decreased below 150 ml X min-1 X kg fetal wt-1. Following repeated injections fetal descending aortic O2 tension and content decreased 34 and 82% respectively, while PCO2 and [H+] increased 28 and 84% respectively. Placental diffusing capacity for CO increased 117% after repeated embolization. Most of this increase could be accounted for by the fetal hypoxia and acidosis, although some of it may have resulted from distension or recruitment of vessels in the placental exchange area, or a more uniform distribution of placental blood flows. These studies suggest that the acute changes in fetal blood gas values following embolization result from a reduction in blood flow rather than from a reduced placental exchange area.

Animals↗

Maternal blood volume and cardiac output during pregnancy: a hypothesis of endocrinologic control.

During the course of gestation the increase of maternal total blood volume and cardiac output may result from two mechanisms acting in concert: 1) the production of several hormones by the fetus and the placenta, and 2) the uteroplacental circulation acting as an arteriovenous shunt. Plasma volume appears to increase as a consequence of renal Na+ reabsorption and water retention, which result from increased aldosterone production via the renin-angiotensin system, as a consequence of placental estrogen production. This estrogen production in turn results from increasing availability of the estrogen substrate dehydroepiandrosterone (chiefly from the fetal adrenal gland). Erythrocyte volume increases as a consequence of the erythropoietic effect of placental chorionic somatomammotropin, progesterone, and perhaps prolactin. In addition, maternal blood volume increases in response to the uteroplacental circulation functioning as a low-resistance circuit. In turn, this increases cardiac output and nutrient delivery for further growth of the products of gestation. Thus there may exist a feedback mechanism whereby fetal growth and, in particular, increasing steroidogenesis by the developing fetal adrenal gland result in the maternal cardiovascular adaptations to pregnancy that optimize further fetal development. In certain complications of pregnancy the less-than-normal maternal blood volume increase may result from failure of these mechanisms, while in turn contributing to the further genesis of these disorders.

Animals↗