Biomedical subjects

L D Longo

Publications and source records attributed to L D Longo.

At least 91 records · Page 5Linked to original sources

PubMed1989

Errors in microsphere determination of cardiac output: a computer simulation in fetal sheep.

Through use of a compartmental model, we simulated the measurement of cardiac output and distribution by means of radioactively labeled microspheres in fetal lambs with weights between 0.5 and 3 kg. A systematic error in measured cardiac output caused by artifactual changes in blood volume caused by the injection and withdrawal of fluids during the procedure was less than 5% for fetal weights greater than or equal to 1 kg but increased for fetal weights less than 1 kg and when hypovolemia was simulated at all fetal weights. Sensitivity analysis disclosed no significant effect of changes in vascular resistance. We examined the effects of recirculation of microspheres and found no significant increase in error in the measured value of cardiac output due to 20% recirculation of all spheres entering a single isolated organ system; however, errors between 7 and 14% were observed with simulations of 20% recirculation in more than one compartment simultaneously. Recirculation also introduced significant errors in the measured distribution of cardiac output in certain cases. The effect on the measured cardiac output of a temporary change in the true cardiac output was dampened by the artifactual blood volume changes mentioned above and the fact that the measurement is a time-weighted average. We also evaluated four different experimental designs. We conclude that the microsphere technique provides a remarkably reliable means of quantifying cardiac output and individual organ flow in the fetus. The nonrandom errors inherent in the procedure examined in this study are of the order of 10%, which is likely to be less than the moment-to-moment variation in the true cardiac output.

Algorithms↗

PubMed1989

Cardiac function during long-term hypoxemia in fetal sheep.

To examine right ventricular function during long-term hypoxemia, we instrumented 12 fetal sheep with intravascular catheters and an electromagnetic flow probe on the pulmonary artery. In six cases, hypoxemia was induced by infusing N2 gas into the maternal trachea for 2 wk. Maternal arterial PO2 was less than 60 Torr, and fetal arterial PO2 was reduced from approximately 26 to approximately 19 Torr. Six cases served as nonhypoxic controls. We studied fetal cardiac function by increasing either preload with a volume infusion of 5% (wt/vol) dextrose or afterload by administering methoxamine (alpha-adrenergic agonist). In hypoxic animals, right ventricular output (QRV) and stroke volume (SV) were not affected on the first 2 days but fell 30% on day 3. Fetal arterial pressure (Pfa) increased 20%, hemoglobin concentration increased approximately 30%, and fetal heart rate (FHR) showed minimal changes. Within 2 wk, QRV recovered to normal values, whereas ventricular sensitivity to arterial pressure was reduced. We observed no change in plasma concentration of "cardiac enzymes" or differences in fetal growth between groups. In conclusion, during prolonged hypoxemia, right ventricular function showed a triphasic response (primary maintenance, secondary depression, and subsequent recovery), achieving a new steady state 2 wk after the start of hypoxia, characterized by decreased sensitivity to afterload, associated with polycythemia and hypertension.

Animals↗

PubMed1989

Maternal responses to long-term hypoxemia in sheep.

To determine the maternal cardiovascular responses to long-term hypoxemia, we studied three groups of animals: 1) pregnant ewes (n = 20) at 110-115 days gestation subjected to hypoxia for up to 28 days; 2) pregnant ewes (n = 4) that served as normoxic controls; and 3) nonpregnant ewes (n = 6) subjected to hypoxemia for up to 28 days. We measured mean arterial pressure, heart rate, uterine blood flow, and uterine vascular resistance continuously for 1 h/day while the ewe was exposed to an inspired O2 fraction of 12-13% for at least 17 days. Arterial PO2, O2 saturation, hemoglobin, arteriovenous O2 difference, and uterine O2 uptake were measured daily while blood volume and erythropoietin concentration were measured weekly. In the pregnant hypoxic group arterial PO2 decreased from a control value of 101.5 +/- 5.1 to 59.2 +/- 5.1 Torr within a few minutes, where it remained throughout the study. The hemoglobin concentration increased from 8.9 +/- 0.5 to 10.0 +/- 0.5 g/dl within 24 h where it remained, whereas erythropoietin concentration increased from 16.6 +/- 2.1 to 39.1 +/- 7.8 mU/ml at 24 h but then returned to near-control levels. Arterial glucose concentration, mean arterial pressure, and cardiac output decreased slightly but insignificantly. In contrast, body weight, heart rate, blood volume, uterine blood flow, uterine O2 flow, uteroplacental O2 uptake, and the concentrations of catecholamines and cortisol remained relatively constant. Thus both pregnant and nonpregnant sheep experience relatively minor cardiovascular and hematologic responses in response to long-term hypoxemia of moderate severity.

Animals↗

PubMed1989

Fetal responses to long-term hypoxemia in sheep.

The effect of acute or short-term hypoxia on fetal cardiovascular hemodynamics has been well known; however, little is known about the effect of long-term hypoxemia. To determine the fetal hemodynamic responses to this stress we studied two groups of animals: 1) pregnant ewes (n = 20) at 110-115 days of gestation subjected to hypoxia for up to 28 days and 2) pregnant ewes (n = 4) that served as normoxic controls. We chronically catheterized the fetal brachiocephalic artery and vein. Five to 6 days after surgery, control measurements were made of mean arterial blood pressure, heart rate, arterial PO2, O2 saturation, hemoglobin, hematocrit, blood volume, and the concentrations of erythropoietin, cortisol, epinephrine, and norepinephrine. The next day the ewes were placed in a chamber with an inspired O2 fraction of 12-13%. Within a few minutes fetal arterial PO2 decreased from control value of 29.7 +/- 2.1 to 19.1 +/- 2.1 Torr, where it remained. Hemoglobin increased from 10.0 +/- 1.0 to 12.9 +/- 1.9 g/dl by day 7, where it remained. This was associated with an increase of erythropoietin from 22.8 +/- 2.2 to 144 +/- 37 mU/ml within 24 h, but by day 7 it had returned to levels slightly above normal. Epinephrine also increased moderately and remained elevated throughout the study. However, values of mean arterial pressure and heart rate did not differ from controls. Perhaps surprisingly, these fetuses were able to compensate so that at term their body weights were normal, 3.77 +/- 0.2 kg.

Animals↗

PubMed1989

A microcomputer program for real-time data acquisition in the perinatal physiology laboratory.

This report describes a real-time data acquisition system using the IBM PC-AT microcomputer, and software specifically engineered for the perinatal physiology laboratory. The system samples up to sixteen analog signals at a rate ranging from 1 to 1024 Hz. Calibrated digital values are displayed on the computer monitor and stored on disk. The system can perform algebraic computations and estimate derivatives. Pattern recognition algorithms are included for the detection and characterization of uterine contractions and fetal breathing movements. Two different noise-rejection filters are implemented. Output of signals via a digital-to-analog converter is supported. The system has been used to record a broad variety of physiologic variables in a number of different studies.

Algorithms↗

PubMed1988

Fundamental and clinical research and patient care: a triad for progress in reproductive medicine.

This essay reviews select instances in the modern history of reproductive medicine, with particular emphasis on the past 25 years since the establishment of the National Institute of Child Health and Human Development. It considers five examples of how fundamental and clinical research have contributed to patient care and, in turn, received stimulus from them; that is, fertility regulation and reproductive endocrinology, prematurity and the initiation of parturition, antenatal testing of fetal maturity, antenatal diagnosis, and neonatal intensive care. Finally, some lessons regarding the interrelationships between research and clinical obstetrics and gynecology are considered.

Female↗

PubMed1988

Effect of maternal pinealectomy and reverse photoperiod on the circadian melatonin rhythm in the sheep and fetus during the last trimester of pregnancy.

The present study tested the hypothesis that the nocturnal melatonin rhythm in the fetal sheep results from transfer across the placenta of melatonin from maternal circulation. Pregnant ewes were exposed to an artificial reverse photoperiod at about 100 days gestation (n = 6; lights on 10 h, 2200-0800 h PST). This treatment tested for entrainment in the ewe and its fetus of the 24-h pattern of melatonin production from the pineal gland. Other ewes were pinealectomized at 55 days post-breeding (n = 6), and similarly treated. Catheters were implanted and blood samples were collected between 117 and 142 days gestation at two 48-h periods, about every 0.5-4 h, to assess the pattern of melatonin in maternal and fetal circulations. In pineal-intact ewes and their fetuses, melatonin rhythms conformed to the reverse photoperiod, i.e. plasma melatonin concentrations were relatively low during the light period and significantly increased for the duration of darkness. In contrast, maternal pinealectomy abolished the melatonin rhythms in both the ewe and fetus; melatonin concentrations remained at or below the limits of detection. Pineal-intact sheep gave birth about 139 +/- 2 days (mean +/- SE, n = 4) at 1915 +/- 0.7 h and pinealectomized ewes (n = 5 of 6) lambed at 149 +/- 2 days at 0424 +/- 0.5 h. Finally, in lambs (n = 3) born to pinealectomized ewes, typical melatonin rhythms were present within the first week of life. The findings indicate that the maternal pineal gland is responsible for the 24-h pattern of melatonin in the ewe and its fetus during the last trimester of pregnancy.

Animals↗

PubMed1988

Effect of nimodipine on newborn lamb cerebral blood flow.

The effects of nimodipine, on total and regional cerebral blood flow and cardiovascular function of the newborn chloralose-anesthetized lamb were investigated following intravenous bolus infusions (0.2, 0.6 and 2.0 micrograms/kg). At 2.0 micrograms/kg, the mean arterial blood pressure increased from 72.3 to 85.8 mm Hg. Total cerebral blood flow 45 min after infusion increased by 93%, as did regional flows to the gray (101%) and white (77%) matter and subcortex (108%). In a separate series of experiments we decreased arterial blood pressure from 71 to 40 mm Hg by phlebotomy. Nimodipine (30 micrograms/kg) bolus infusion significantly increased blood flow above control values to the total brain (41%), gray matter (53%), subcortex (76%) and brainstem (69%) 10 and 40 min later. However, no further increase in flow or decrease in cerebrovascular resistance was observed when compared to hypotension alone. Nimodipine appears to be well tolerated in the newborn lamb, and appears to increase cerebral flow during normotension. At the levels of hypotension used in the current experiments, nimodipine produced no further increases in cerebral blood flow.

Animals↗

PubMed1988

Fibroblast growth factor enhances human chorionic gonadotropin synthesis independent of mitogenic stimulation in Jar choriocarcinoma cells.

The Jar choriocarcinoma cell line was used as an in vitro placental cell model to determine the effects of polypeptide growth factors on hCG beta secretion. Epidermal and fibroblast growth factor (FGF) treatment of serum-free cultures stimulated hCG beta secretion 2.5- and 4.0-fold over basal serum-free control levels within a 15-h incubation period. Insulin-like growth factor I, nerve growth factor, and transforming growth factor-beta had no significant effect on hCG beta secretion. FGF at concentrations as low as 0.125 ng/ml significantly elevated medium hCG beta levels without increasing cell number or total cellular protein. FGF stimulation of secretion was not detectable until 2 h of treatment. Intracellular hCG beta remained constant (23%) relative to total hCG beta (cell plus medium) as total hCG beta increased 3-fold, suggesting that FGF stimulated de novo hCG beta synthesis. Insulin significantly augmented the FGF-induced hCG beta stimulation without stimulating hCG beta production itself.

Choriocarcinoma↗

PubMed1988

Fetal breathing adaptation to prolonged hypoxaemia in sheep.

Prolonged (6 days) fetal hypoxaemia was produced by placing pregnant ewes in an environmental chamber. A constant flow of N2 into the chamber reduced the fraction of inspired oxygen (Fi02) to 0.139 +/- 0.001, simulating an altitude of 4270 m. This reduced maternal PaO2 by about 39 mmHg and PaCO2 by nearly 5 mmHg, which produced a hypocapnic (delta PaCO2 = -5 mmHg) hypoxaemia (delta PaO2 = -8 mmHg) in the fetus. An analysis of the first 4 h of breathing recorded each day (1800-2200 h; start of hypoxaemia: 1200 h) showed that the incidence (12 +/- 2.0 min/day) during the first day of hypoxaemia was significantly less (P less than 0.05) than that (24 +/- 3.1 min/h) during the same time of the control day. By the second day, breathing had returned to normal. Further analysis indicated that a normal incidence of breathing may have occurred as early as 14 h after starting hypoxaemia. These results suggest that fetal breathing movements adapt rather quickly to this degree of hypocapnic hypoxaemia.

Acclimatization↗

PubMed1988

[Transplacental gas exchange].

Fetal oxygenation depends on that of the mother by the intermediary of the placenta. The respiratory feto-maternal gas exchanges are reviewed as are the regulatory factors. The greater part of the data reported here comes from experimentation of pregnant animals near term. The most important parameters for fetal oxygenation are the maternal and fetal O2 partial pressures, the affinity of the blood for oxygen, the maternal and fetal placental blood flow and the quantity of CO2 exchanged. Finally, placental efficiency as regards gas exchanges is compared to the lung.

Carbon Dioxide↗

PubMed1987

Melatonin rhythms in fetal and maternal circulation during pregnancy in sheep.

In many seasonally breeding species, the nocturnal melatonin rhythm is part of an endogenous biological clock mediating information about day length to time the onset of puberty and the annual adult reproductive cycle. To determine whether timekeeping persists during pregnancy, we studied the pattern of melatonin in circulation in sheep during the last trimester of gestation. We measured plasma melatonin concentrations in the chronically catheterized ewe and fetus (n = 6) over a 48-h period (every 1-4 h) at approximately 120 days gestation. A typical rhythm was present in the pregnant ewes; plasma melatonin was low during the day and remained increased throughout the night. In the fetus, a modest 24-h pattern was detected, which lagged 0.5-1.5 h behind that of the maternal circulation. In combination with findings later in gestation (126 and 135 days) or even during parturition, it is clear that melatonin rhythms were sustained in all pregnant ewes and a 24-h pattern was present in the fetus. In those sheep that went to full term, births occurred during the night at 0130 +/- 2.6 h (mean +/- SE, n = 3). These findings suggest that measurement of day length is maintained in female sheep during the last trimester of pregnancy. Moreover, information about day length and/or time of day may be transferred across the placenta, because the pattern of melatonin in fetal circulation follows the maternal circadian melatonin rhythm.

Animals↗

PubMed1987

Amniotic fluid volume regulation: basal volumes and responses to fluid infusion or withdrawal in sheep.

To better understand the mechanisms that regulate amniotic fluid (AF) volume, we measured AF volume and the rates of fetal swallowing and urination in 33 pregnant sheep at 124-142 days gestation. In four of five ewes over 9-18 days, the spontaneous changes in amniotic fluid volume correlated positively with urine flow rate and negatively with the rate of swallowing (R = 0.686, P less than 0.01), such that 47% of the AF volume changes could be attributed to changes in rates of urination and swallowing. Following infusion of one liter of isotonic amniotic saline (n = 12) or mannitol (n = 5), AF volume increased 110%, and after 24 h returned to the control value in the saline group but it remained elevated 59% above control in the mannitol group. AF sodium was unchanged following saline infusion but remained reduced following mannitol. Following withdrawal of 61% of AF over 20-40 min, AF volume averaged 51 and 71% of control at 24 and 48 h, respectively, whereas AF sodium was unchanged. Variations in rates of fetal swallowing or urine formation could not explain the entire changes in AF volume following either the volume infusion or withdrawal. These data suggest that AF volume is regulated within a relatively narrow range and fetal urine formation and swallowing together and transplacental fluid flux each appear to contribute equally to the regulation of AF volume.

Amniotic Fluid↗

PubMed1987

Lymphatic and vascular responses to fluid infusion in castrated and noncastrated sheep.

Estrogen administration produces blood volume expansion and interstitial fluid retention. We decided to study the effect of estrogen withdrawal on blood volume and determine whether oophorectomy has an effect on lymph flow or protein concentration. The rate of left thoracic duct lymph flow averaged 0.041 +/- 0.005 (SE) and 0.071 +/- 0.008 ml X min-1 X kg-1 in castrated (n = 9) and noncastrated (n = 9) female sheep, respectively (P = 0.006). After three serial intravenous infusions of Ringer lactate solution (2% body wt/infusion) the thoracic duct lymph flow in the castrated animals increased 358, 457, and 498% over the base-line rate, compared with increase of 200, 235, and 353% in the nonpregnant ewes. However, with the lower control values in the castrated animals, the lymph flow rate reached the same absolute values as those seen in the noncastrated ewes. Lymph protein concentration and the lymph-to-plasma protein concentration ratio, as well as arterial and venous pressures, were unaltered by oophorectomy. Base-line whole blood volumes were 58.2 +/- 1.9 (n = 9) and 64.8 +/- 2.6 ml/kg (n = 9) in the castrated and noncastrated ewes, respectively (P less than 0.05). Systemic vascular compliance averaged 4.5 +/- 0.7 and 7.1 +/- 1.7 ml X kg-1 X mmHg-1 in the castrated and noncastrated ewes, respectively (P less than 0.05), whereas interstitial fluid compliance values were 12 and 32 ml X kg-1 X mmHg-1, respectively. The capillary filtration coefficients were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Physiologic assessment of fetal compromise: biomarkers of toxic exposure.

Understanding the physiologic and endocrinologic basis of fetal development is a major goal of perinatal biology. During the past decade a number of technological developments have allowed more precise evaluation of the fetus in utero and diagnosis of abnormalities. Despite these methodological achievements, however, there are no specific biological markers currently available to indicate that exposure to a given xenobiotic is associated with a cellular, subcellular, or pharmacodynamic event. This paper evaluates the following issues: What are some of the unique physiologic and endocrinologic features of the fetal milieu intérieur? What problems are peculiar to fetal assessment? Of what value are techniques such as ultrasonography, amniocentesis, chorionic villus sampling, fetoscopy, and fetal blood and tissue sampling for obtaining appropriate biomarkers? What are some examples of validated biomarkers and their applicability? What promising biomarkers are on the horizon? What are some of the promising techniques such as the evaluation of fetal body movements, breathing activity, electronic heart rate monitoring, and nuclear magnetic resonance? How may molecular probes be of value as biological markers of fetal compromise? What are some of the major research gaps and needs, and how should research priorities be set? Some of these topics are addressed. Moreover, the more general role(s) that various diagnostic methods and biological markers can have in an understanding of the regulation of fetal growth and differentiation and the role of xenobiotics in affecting the normal course of events are discussed.

Abnormalities, Drug-Induced↗

PubMed1986

Estrogen effects on plasma volume, arterial blood pressure, interstitial space, plasma proteins, and blood viscosity in sheep.

In adult castrated ewes the infusion of 17 beta-estradiol for 3 weeks was associated with a 12% increase in body weight, a 20% increase in whole blood volume (mainly due to a 27% increase of plasma volume), a 13% decrease in mean arterial blood pressure, and a 40% increase in heart rate. The change in plasma volume correlated with the change in estradiol concentration (r = 0.72). Most of the fluid was retained in the interstitial space, as represented by a 6 kg weight gain, 10% of which was in the intravascular compartment. Whole blood and plasma viscosity increased 16% and 21%, respectively, thus reversing some of the blood volume effects toward a hyperdynamic cardiovascular state. We conclude that many of the cardiovascular and hematologic changes with estrogen administration are similar to the changes observed during pregnancy, with the proposed requirement of decrease in mean arterial blood pressure as a condition for blood volume expansion.

Animals↗

PubMed1986

Uteroplacental unit as a source of elevated circulating prorenin levels in normal pregnancy.

Circulating levels of inactive renin, that is, prorenin, are increased in normal pregnant women. To determine whether the uteroplacental unit secretes prorenin into the maternal circulation, we measured enzymatically active and inactive renin in plasma simultaneously obtained from the radial artery and uterine vein of 12 normotensive, nonlaboring patients undergoing elective cesarean section at term. We also measured these forms of renin in the umbilical arterial and venous blood of these patients. Our data reveal that the levels of inactive renin in both arterial and uterine venous blood of normal pregnant women are significantly higher than in peripheral venous blood of nonpregnant, normotensive control subjects; normotensive term patients have a ratio of plasma inactive to active renin of 9:1 in contrast to the 1:1 ratio in normotensive nonpregnant subjects; there is a significant uterine arteriovenous difference of prorenin (66.2 +/- 24.4 ng/ml/hr, p less than 0.05) but not of active renin (1.8 +/- 1.5 ng/ml/hr, not significant). These results suggest that the uteroplacental unit contributes to the elevated prorenin levels at term pregnancy.

Cesarean Section↗

PubMed1986

Uteroplacental O2 uptake: continuous measurements during uterine quiescence and contractions.

To determine the constancy of uteroplacental O2 uptake (VO2) during uterine quiescence and both spontaneous and oxytocin-induced uterine contractions, we have developed a method to measure VO2 continuously and reproducibly. In seven ewes during uterine quiescence, total uterine blood flow (Qut) averaged 200 ml X min-1 X kg uterine contents-1, with intra-animal SD of 18 min X min-1 X kg-1 and interanimal SD of 86 ml X min-1 X kg-1. Uterine arteriovenous O2 content difference averaged 4.2 +/- 0.5 ml X dl-1. VO2 averaged 8.2 +/- 1.2 ml X min-1 X kg-1, with interanimal SD of 3.6 ml X min-1 X kg-1. During 21 spontaneous prelabor contractions, VO2 decreased 3.8% to 8.7 +/- 0.3 ml X min-1 X kg-1 (NS) during the contraction and subsequently increased 12.3% to 10.1 +/- 0.3 ml X min-1 X kg-1 (P less than 0.05) near the end of the contraction. With oxytocin-induced contractions, VO2 fell 10% to 6.4 +/- 0.2 ml X min-1 X kg-1 at the contraction onset (P less than 0.05) but by the end of the contraction had increased 6.1% to 7.6 +/- 0.2 ml X min-1 X kg-1 (NS). In conclusion, uteroplacental VO2 was measured continuously and reproducibly using relatively straightforward methodology; uteroplacental blood flow, arteriovenous O2 content difference, and uteroplacental O2 uptake were normally distributed with coefficients of variation less than 15%; and during both spontaneous and oxytocin-induced uterine contractions Qut decreased significantly, while VO2 initially decreased moderately and then showed an overshoot, during the contraction.

Animals↗