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Biomedical subjects

R D Gilbert

Publications and source records attributed to R D Gilbert.

At least 55 records · Page 3Linked to original sources

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↗

Computer model of fetal-maternal heat exchange in sheep.

We constructed and used a mathematical model of maternal-fetal heat exchange in the sheep to explore the effects of changes in certain parameters on steady-state fetal temperatures and to determine whether the fetus in the model has any potential to control its own temperature. The model took into account both fetal and placental heat production and exchange of heat in the placenta, across the fetal skin, via amniotic fluid, and through the uterine wall. The maternal ewe was assumed to be a constant temperature heat sink. Changes in placental or fetal heat production were calculated to change the ratio of heat exiting across the placenta or fetal skin significantly but to have little effect on fetal core temperature, e.g., a rise of only 0.8 degrees C was predicted after a twofold increase in fetal heat production. Fetal placental blood flow was calculated to affect fetal temperature the most of any flow, a reduction to zero causing fetal temperature to rise 5.0 degrees C. Changes in heat conductances between fetal skin and amniotic fluid, or between amniotic fluid and uterine wall, had minimal effect on fetal temperature. From the model calculations here and because heat exchange within the sheep placenta has previously been calculated to be extremely efficient, we conclude that the fetal sheep has little ability to control its temperature by changes in heat dissipated through extraplacental pathways. Thus the model predicts an effective heat clamp that closely links fetal to maternal temperature.

Animals↗

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↗

In vivo brown fat response to hypothermia and norepinephrine in the ovine fetus.

The goal of this study was to assess the response of fetal brown fat in vivo to hypothermia and norepinephrine infusion. In 10 unanaesthetized, chronically-prepared fetal sheep (133 +/- 2 days of gestation) cold water was passed through tubing encircling the fetus in utero and plasma glycerol concentration was measured as an indicator of brown fat activity. Following cooling for 60 min, amniotic fluid temperature fell 7.79 degrees C to 31.66 +/- 1.73 degrees C (n = 8, P less than 0.001) and maternal temperature fell 0.63 degree C to 38.63 +/- 0.08 degrees C (n = 9, P less than 0.001). Eight of the fetuses were subjected to a second experiment in which norepinephrine was infused intravenously for 15 min. During infusion fetal arterial temperature fell 0.38 degrees C to 39.05 +/- 0.25 degrees C (n = 7, P less than 0.05). Amniotic fluid temperature (n = 7, NS) and maternal arterial temperature (n = 7, NS) remained constant. Glycerol concentration during the infusion increased from 0.73 to 1.27 mg/dl, a 74% increase over control (n = 8, P less than 0.001). Although clearly detectable, these glycerol responses to hypothermia and norepinephrine stimulation are one-third or less of those achieved after birth, indicating that thermogenesis remains quiescent in the near-term fetal sheep, despite powerful stimuli for activation.

Adipose Tissue, Brown↗

Acute promyelocytic leukemia. A childhood cluster.

Nine children with acute promyelocytic leukemia (APL) are presented. This series of children represents 7% of all acute leukemias and 21% of acute myelogenous leukemias seen during the same period at the Red Cross War Memorial Children's Hospital. These figures are much higher than the incidence quoted in other series of childhood leukemia. In addition, most of those children came from a confined geographic area. Two of the patients were younger than 2 years of age. The youngest patient with APL previously reported in the literature was 24 months.

Bone Marrow↗

Nifedipine: effects on fetal and maternal hemodynamics in pregnant sheep.

We investigated the effects of nifedipine, a calcium entry blocker, on the fetal and maternal circulation. Nifedipine was administered intravenously for 30 minutes to chronically instrumented pregnant ewes. Infusion of 5 micrograms.kg-1.min-1 resulted in a 30% to 50% increase in total and regional fetal cerebral blood flow to the brain stem, watershed, and subcortical regions (p less than 0.05), without a significant change in fetal oxygenation or cardiac output. Infusion of 10 micrograms.kg-1.min-1 decreased uterine blood flow by 21% (p less than 0.001) and fetal arterial oxygen content by 15% (p less than 0.01), with no further increase in fetal cerebral blood flow. Maternal arterial pressure decreased and heart rate increased (p less than 0.001) without variation of arterial blood gases. Significant plasma levels of nifedipine were detected in the fetal and maternal circulations. In view of the potential adverse effects on the fetus, further studies are needed before nifedipine is considered for use in human pregnancy.

Animals↗

Postnatal change of cardiac function in lambs: effects of ganglionic block and afterload.

This study characterizes the maturational change of cardiac function in unanaesthetized lambs from 1 day to 6 months of age. The cardiac function curve, the relationship between left ventricular output (Qco) and left ventricular end diastolic pressure, was studied in lambs of ages 1 day, 2-3 days, 7-8 days, 1 month, 3 months and 6 months. Cardiac output was measured by thermodilution while left ventricular end diastolic pressure was either raised by infusion of 5% glucose, or lowered by haemorrhage. At elevated left ventricular end diastolic pressure, cardiac output tended to reach a plateau of approximately 300 ml/min per kg in lambs less than 1 week of age and 200 ml/min per kg in lambs older than 1 month. Cardiac function was depressed by total ganglionic block in 1-3 days-old lambs, but not in lambs older than 1 week. Heart rate decreased in response to ganglionic block in lambs up to 1 week of age, but it increased in lambs 3-6 months old. Increases in afterload with methoxamine infusion during ganglionic block further depressed cardiac function in all age groups of lambs. The stroke work curve was shifted downward by hexamethonium and returned back to control level by methoxamine. We conclude that newborn cardiac output is near maximum even at 1 month of age. Sympathetic activity and circulating catecholamines help maintain cardiac function in 1-3 days-old lambs. Cardiac function is sensitive to afterload in lambs of all ages studied.

Age Factors↗

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↗

Fetal and uteroplacental heat production in sheep.

To separate heat production of the fetus from that of the placenta, endometrium, and uterine muscle, we measured total uterine heat production first with the fetus intact and then after the umbilical cord was snared and the fetus killed. Heat production was measured with the Fick principle using thermistors chronically implanted in a maternal artery and major uterine vein and a flowmeter placed on the common internal iliac artery. In nine ewes, carrying lambs weighing 4.46 +/- 0.42 (SE) kg, total uterine heat production fell from 10.6 to 2.9 W after fetal death. Uterine blood flow fell progressively to 90% of control levels during the first hour after death. The caloric equivalent for O2 averaged 4.1 cal/ml O2 for the uterus, 2.2 for the uteroplacenta, and 4.6 for the fetus per se. It was not possible to explain these results using a simple model of maternal-fetal heat transfer. Rather, it was necessary to assume an additional pathway for heat transfer between small uterine veins on the surface of the uterus and cooler structures in the maternal abdomen, presumably the ventral abdominal wall.

Animals↗

Effect of cooling and heating on the regional distribution of blood flow in fetal sheep.

This is a study on the effect of cooling and heating amniotic fluid on blood flow to fetal tissues and organs. In 8 unanaesthetized, chronically-catheterised fetal sheep (129-137 days gestation) cold or warm water was passed through tubing encircling the fetus in utero and blood flow was measured using the radionuclide-labelled 15 mu spheres. Following cooling for 30 min, amniotic fluid temperature fell 9.6 degrees C to 29.9 +/- 2.1 degrees C (SEM) fetal arterial temperature fell 2.37 degrees C to 37.30 +/- 0.36, and maternal arterial temperature fell 0.53 degrees C to 38.58 +/- 0.16. Blood flow through the fetal skin fell 60% (P less than 0.01) to 13.6 ml/min per 100 g tissue. Blood flow to the brown fat increased 186% (P less than 0.05) to 99.6 ml/min per 100 g. Following warming for 20 min, fetal temperature rose to 40.43 +/- 0.19 degrees C, and skin blood flow did not change significantly relative to initial control period but rose 200% above that during cooling (P less than 0.01). During both cooling and heating, blood flow to the adrenals rose significantly (P less than 0.05) whereas flow to the carcass, brain, kidneys, and placenta was not altered detectably. Continuous sampling of blood from the inferior vena cava during microsphere injection failed to detect any evidence of arterio-venous shunting through the skin at any temperature studied. Overall, the blood flow responses are consistent with a thermoregulatory role for the skin and brown fat in the near-term fetal sheep.

Amniotic Fluid↗

Temperature responses following ventilation of the fetal sheep in utero.

The mammalian fetus produces significant quantities of heat. This passes to the mother principally through the placenta and to a lesser extent via a pathway comprising the skin, amniotic fluid, and uterine wall. To assess the importance of the lesser pathway, temperature responses were recorded in 7 near-term fetal sheep after intrauterine ventilation with oxygen, after snaring the umbilical cord to block the placental route, and following fetal death. Four distinguishing characteristics of responses were observed: fetal temperature rose 0.10 +/- 0.03 (SEM) degrees C after oxygenation; it rose progressively an additional 0.9 +/- 0.1 degrees C during the 90-min interval after cord snaring; amniotic fluid temperature rose slowly until it was about midway between fetal and maternal temperature; and after fetal death, fetal amniotic fluid temperatures fell slowly. In a simple mathematical model with constant parameters these results could not be explained fully. It was necessary to assume that heat production rose with increased oxygenation and elevated body temperature and that ventilation increased heat transfer through the amniotic fluid, as would occur if chest wall movement were stirring the fluid. Using the model, the value for heat conductance from fetal skin to amniotic fluid was estimated to be 10.5 watts degrees C-1 under basal conditions.

Amniotic Fluid↗

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↗

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↗

Heat transfer pathways between fetal lamb and ewe.

Heat produced by the fetus exists to the mother by one of two principal routes: by fetal-maternal exchange in the placenta or through the fetal skin to the amniotic fluid and uterine wall. We measured heat conductances along each pathway to estimate the fraction of total heat exiting each route. Thermistors were placed in the fetal aorta, two different sites in the amniotic fluid, and in a maternal artery. Five days after surgery we injected a total of 280 ml of ice-cold saline into the two separate amniotic fluid sites during a 45-s interval and measured the temperature response for the next hour. After one or two such injections the fetus was killed to cut off umbilical blood flow, and the experiment was repeated to measure the heat fluxes in the absence of placental heat exchange. Experimentally obtained temperature curves were compared with the predictions of a mathematical model. Heat conductances of the skin and uterine wall, as well as the fetal heat production, were estimated in the model using least-squares parameter optimization. In 10 fetal lambs, weighing 3.73 +/- 0.40 (SE) kg, total fetal heat production averaged 3.75 +/- 0.33 W X kg-1. The heat conductance of the uterine wall, 6.6 +/- 0.8 W X degrees C-1, was lower than that of the fetal skin, 10.2 +/- 1.0, and of the placenta, 25.7 +/- 2.9 W X degrees C-1, temperature gradient. We estimated that 84.5% of total fetal heat production exists by fetal-maternal exchange in the placenta with the remaining 15.5% exiting through the fetal skin.

Amniotic Fluid↗

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↗

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↗

Measurement of fetal heat production using differential calorimetry.

These experiments were undertaken to measure heat production of fetal lambs in utero by using differential calorimetry. We used the principle that fetal heat production, H(fetus), can be calculated from measurements of base-line temperature difference between mother and fetus, delta T(fetus), heat introduced from an external source, H(heater), and the increase in body temperature, delta T(heater), that results, i.e., H(fetus) = H(heater) X delta T(fetus)/delta T(heater). We placed microheaters (1.8 mm diam) in the inferior vena cavae of eight near-term lambs and placed thermistors and catheters into maternal and fetal vessels and amniotic fluid. Five days later, fetal arterial temperature averaged 0.54 +/- 0.02 degrees C (SE) higher than maternal arterial temperature. When the heater was turned on to dissipate 29-103 cal/min, fetal temperature increased to approach 0.1-0.5 degrees C higher than control; the final temperature was estimated using the rate of increase during the first 20 min. Fetal heat production averaged 47.1 +/- 4.1 cal X min-1 X kg-1 during the warming phase in these lambs, which weighed 3.26 +/- 0.36 kg. This value would be 3-4% less if corrected for the increase in metabolic rate caused by heating, assuming a Q10 of 2.5. Fetal heating did not alter fetal heart rate, blood pressure, or blood gas values significantly, nor was hemolysis visible in plasma samples. When heat production was calculated from the decrease in fetal temperature after the heater was turned off, an average value of 41.2 +/- 2.5 cal X min-1 X kg-1 was found. Because this value is comparable to the heating phase, fetal metabolic rate and the insulating properties of the fetal shell are not likely to have been changed by the heating.

Animals↗