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Biomedical subjects

G G Power

Publications and source records attributed to G G Power.

At least 73 records · Page 4Linked to original sources

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↗

Thoracic duct lymph flow: a comparative study in newborn and adult sheep.

To understand better developmental changes in body fluid dynamics, we studied thoracic duct lymph flow in 9 newborn and 5 adult sheep. The experiments were carried out under general anaesthesia following bilateral ligation of the renal vessels and ureters. After a 30 min control period, we administered three successive 5-min intravenous infusions of isotonic saline equivalent to 2% of body weight each, at 30-min intervals. The average basal lymph flow rate was 0.157 +/- 0.033 (SEM) ml.min-1.kg-1 and 0.046 +/- 0.018 ml.min-1.kg-1 in newborns and adults respectively (p less than 0.05). Fluid overloading resulted into similar intravascular retentions at the end of each 30-min period in both groups although the increase in lymph flow was repeatedly more than three times higher in the newborns. The more pronounced lymph flow response in the newborns could not be accounted for only on the basis of a difference in capillary filtration. We speculate that interstitial forces and/or the lymphatic pumping activity play a greater role in facilitating fluid movements in the newborn lamb than in the adult ewe. Overall, the higher capacity of the newborn to eliminate excess interstitial fluid constitutes a significant factor in the body's defense against oedema.

Age Factors↗

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↗

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↗

Urinary and hemodynamic responses to blood volume changes in fetal sheep.

Because of the potential importance of the fetal kidney in regulating blood volume and amniotic fluid volume, and their composition, we studied renal and cardiovascular responses to changes in blood volume in 12 chronically-catheterized fetal sheep at 110-135 days gestation. During the hour following volume expansion with 50 ml of maternal whole blood, blood pressure rose by 14%, cardiac output by 11%, renal blood flow by 68% and urine output by 36%. Packed red cell volume rose from 31.3 to 34.0%, suggesting a net fluid loss from the circulation through the kidneys, as well as through peripheral and placental capillaries. During the hour following volume depletion by haemorrhage of 70-120 ml, blood pressure fell by 17%, cardiac output by 29%, renal flow by 46%, glomerular filtration rate by 19%, and urine output by 76%, compared to the preceding phase of the study. The urine-to-plasma osmolality ratio approached unity and urine sodium and U/Pcreatinine increased sharply. Following haemorrhage, fluid rapidly entered the circulation as evidenced by falling packed red cell volume and plasma protein concentration. The data support the hypothesis that the fetal kidney, although immature in some respects, effectively responds to maintain blood volume in the fetal sheep.

Animals↗

Does the autonomic nervous system regulate whole-body lymph flow?

We compared whole-body lymph flow responses with and without the autonomic nervous system intact in pentobarbital-anesthetized, acutely nephrectomized dogs. We measured left thoracic duct lymph flow, lymph and plasma protein concentrations, arterial and venous pressures, heart rate, and hematocrit in eight intact and six ganglion-blocked (hexamethonium, 15 mg/kg iv) animals. Ganglionic blockade lowered arterial pressure and heart rate but did not change lymph flow rate or the other variables. In the control and blocked groups at 30-min intervals, isotonic saline, lactated Ringer, and Dextran 70 solutions were serially infused, followed by hemorrhage and reinfusion of shed blood. Infusions or withdrawals were equal to 2% of body weight and were induced over 5-min intervals followed by 25 min of recovery. Lymph flow generally increased to a peak 5-7 min after each infusion was ended and then decayed back toward preinfusion levels; the extent of the rise in lymph flow, the time of the peak flow, and the extent of decay after the peak were unaffected by autonomic blockade. The absolute lymph flow rates in response to the infusions, hemorrhage, or blood infusion were not appreciably altered by ganglionic blockade. Thus the present studies provide little support to the hypothesis that the autonomic nervous system contributes to whole-body lymph flow.

Animals↗

Effects of hypotonic, isotonic, and hypertonic fluids on thoracic duct lymph flow.

To test whether whole-body lymph flow responses to vascular volume loading depend on osmolality, we measured left thoracic duct lymph flow rate and protein concentration, plasma protein concentration, plasma osmolality, hematocrit, and arterial and venous pressures in pentobarbital-anesthetized, acutely nephrectomized dogs. Hypo- (100 mosmol), iso- (309 mosmol), and hypertonic (600 mosmol) saline, isotonic lactated Ringer solution, and 5% glucose in lactated Ringer solution (580 mosmol) were infused into the jugular vein (20 ml/kg per infusion over 5 min at 30-min intervals). Changes in blood, interstitial, and cellular volumes were calculated from the infused volume and from the hematocrit and plasma osmolality. The hypotonic fluid increased lymph flow about half as much as the isotonic fluid, whereas the hypertonic fluids increased lymph flow about twice as much as the isotonic infusions. Responses appeared independent of the osmotic agent, because hypertonic NaCl was as effective as hypertonic glucose in increasing lymph flow. Responses were not altered appreciably after lowering arterial pressure by 25 mmHg. The major finding of this study is that for every condition we explored, the excess lymph flow over 30 min (ELF in ml X kg-1 X 30 min-1) correlated with the change in interstitial fluid volume (delta ISFV in ml/kg); ELF = 0.076 delta ISFV (r = 0.909). These data suggest that cellular fluid that enters the interstitium is equally effective in increasing thoracic duct lymph flow as is vascular fluid that filters into the interstitium.

Animals↗

Changes in permeability of fetal guinea pig skin during gestation.

Permeability of fetal skin to tritiated water was measured in vitro using samples taken from the back and flanks of 21 guinea pig fetuses whose gestational age ranged from 30 to 67 days (term = 68 days). From 30 to 45 days, fetal skin was relatively permeable to water, with a permeability coefficient for unidirectional, diffusional transfer of labelled water that averaged 0.372 +/- 0.041 (SEM) X 10(-4) cm/s. Then during a 5-10 day interval, the measured permeability coefficient decreased abruptly to very low and barely detectable levels. These changes took place at the time during gestation when others have shown the skin becomes keratinized and growth of new hair follicles is completed. Thus these findings are consistent with a relatively free exchange of water between amniotic fluid and fetal interstitium across the skin during the first two-thirds of gestation and then with further maturation an abrupt functional separation between these fluid compartments during the last third of gestation.

Amniotic Fluid↗

Distribution of maternal and fetal blood flow within cotyledons of the sheep placenta.

These studies explore the distribution of blood flow among small samples of placental tissue. Labeled microspheres (14 +/- 1 micrometers, SD) were injected into the left ventricle of six unanesthetized ewes and into the jugular vein of the fetuses in utero. A total of 3,576 samples weighing 31 +/- 11 (SD) mg were taken from 17 cotyledons and counted for flow labels. Maternal and fetal blood flow within the cotyledons were both normally distributed with standard deviations of 44%. The maternal-fetal blood flow ratio was less than 0.5 in 9% of the cotyledon, between 0.5 and 1.5 in 70%, and greater than 1.5 in 21%. Errors caused by the method were estimated to contribute less than 10% of the flow variances. Maternal and fetal blood flows were significantly correlated (r = 0.57, P less than 0.001), and both exhibited spatial organization. Calculations based on mathematical models suggested that the observed distribution of the ratio of maternal to fetal blood flow may explain about 50% of the uterine-umbilical venous oxygen tension difference. It was concluded that the samples studied were small in comparison with the dimensions of placental oxygen exchange but may have been similar in size to the dimensions of blood flow control.

Animals↗

Thoracic duct lymph flow and protein flux dynamics: responses to intravascular saline.

Fluid and protein flux responses in the left thoracic duct and vasculature were measured in pentobarbital-anesthetized, nephrectomized, adult dogs before and after four successive intravascular saline infusions of 2% of body weight each. We found three main characteristics of the thoracic lymph flow and protein flux responses to the intravenous saline: 1) lymph flow reached a peak and then decreased by approximately 40% after each infusion; 2) the maximum lymph flow occurred 5-7 min after terminating each infusion; and 3) the lymph-to-plasma protein concentration ratio fell more than may be expected from the distribution of the infused saline. We were unable to explain these experimental data with a simple two-compartment mathematical model representing the vascular and interstitial spaces. To adequately explain the data, the model had to be expanded to four compartments representing a vascular compartment, two interstitial compartments each with different capillary protein permeabilities, and a lymphatic compartment. We also found it necessary to include interstitial stress relaxation, a nonlinear function curve for lymph flow versus interstitial fluid pressure, and a complaint lymphatic system.

Animals↗

Compliance of the fetal sheep liver.

To estimate the importance of the liver as a fetal blood reservoir, we measured the compliance of the liver in eight near-term fetal sheep in utero. Balloon-tipped catheters were positioned above and below the entry of the hepatic veins into the inferior vena cava. Then the hepatic artery and portal vein were ligated and a flow probe placed around the common umbilical vein, the only remaining blood supply to the fetal liver. The balloons were inflated to block hepatic outflow momentarily while flow into the liver and pressure at the outflow of the liver were recorded continuously. Compliance was obtained from the pressure--volume curves and averaged 3.74 +/- 0.49 (SEM) ml/mmHg per 100 g of liver or 1.02 +/- 0.09 ml/mmHg per kg body weight. We were able to simulate these responses with a simple mathematical model of the hepatic circulation with constant compliance and pre- and post-sinusoidal resistances to blood flow. In a second group of none fetal sheep in utero whole body vascular compliance was estimated by measuring the venous pressure rise following the infusion of 60 ml of warm 5% (w/v) glucose in water during a 20 s interval. Whole body compliance averaged 3.66 +/- 0.37 ml/mmHg per kg body weight. Thus, the liver is responsible for about 28% of the whole body compliance on the fetal sheep and may function, therefore, as a significant blood reservoir.

Animals↗

Fetal cardiac output measured by four-way thermodilution.

To measure fetal cardiac output by thermodilution, we injected 2.5 ml of iced 5% glucose rapidly into the superior vena cava and recorded areas of temperature-time curves in the brachiocephalic artery (AS) and descending aorta (BS). One minute later we repeated the injection into the inferior vena cava and recorded areas under two curves (AI and BI). Cardiac output was calculated as Qco = H (AS + BI - AI - BS) (ASBI - AIBS), where H is the change in caloric content of the blood. In a mechanical model we found thermal results correlated well with timed collections (r = 0.98) with a slope of 0.995. In 7 acutely prepared fetal lambs, electromagnetic flow probe measurements of total cardiac output (descending aorta + brachiocephalic artery) correlated well (0.90) with thermal measurements. The slope (1.16) was significantly greater than 1.0, reflecting the inclusion of coronary and pulmonary flows in thermal, but not in flow probe, measurements. In 11 acutely and chronically prepared fetal lambs, the correlation between microsphere and thermal measurements was 0.81 with a slope of 1.09, not significantly different from 1.0. Hence, thermodilution gives results comparable to other methods and is convenient, indefinitely repeatable, inexpensive, and nonradioactive.

Animals↗

Maternal placental vascular compliance in rabbits.

We studied compliance on the maternal side of the placenta of 20 New Zealand white rabbits, using 51Cr and 125I labels to determine erythrocyte, plasma, and whole-blood volumes per gram of placental tissue under varying maternal pressure conditions. At normal maternal arterial (Pa) and venous (Pv) pressures of 71.8 and 5.5 mmHg, placental blood volume (mean +/- SE) was 0.447 +/- 0.051 ml/g placental tissue. When venous pressure was raised (Pa = 45.5, Pv = 12.2) by occluding the inferior vena cava, blood volume increased to 0.729 +/- 0.068 ml/g, a significant 63% rise. However, when arterial pressure was lowered by occluding the aorta in two steps, dropping to Pa = 33.8, Pv = 7.0, and Pa = 13.5, Pv = 5.4, volume did not decrease significantly. We estimated intervillous space pressure (Pivs) from arterial and venous pressures assuming a ratio of venous to total resistance of 0.02. Compliance calculated from the slope of Pivs vs. volume was 0.0471 ml/mmHg per g. Maternal placental hematocrit averaged 27%, appreciably less than the circulating hematocrit of 38%. Overall, the results suggest that placental volume would be maintained during hypotension and would increase when venous pressure is elevated.

Animals↗

Water exchange in the placenta: a mathematical model.

To better understand the complicated interplay of forces affecting human placental water exchange, we developed a system of differential equations describing the flows of water, glucose, bicarbonate ion, amino acids, CO2, O2, passive cations (such as Na+ and K+), and chloride ion transplacentally and across the erythrocytes. The equations are based largely on the flux equations of irreversible thermodynamics, although Goldman's hypothesis and equation are employed to treat the ionic currents across the erythrocyte membrane. Bicarbonate ion and dissolved carbon dioxide were found to be major forces acting early in capillary transit to produce a large flow of water toward the fetus. Near the end of the capillary an almost equal amount of water returns to the mother, an effect due predominantly to the effect of glucose. For small deviations from accepted normal values, water transfer is most sensitive to changes in passive cations and chloride, followed by bicarbonate and CO2, plasma solutes (including lactate and glucose), hydrostatic pressure, and amino acids. A simple equation is given to summarize the model's results for water transfer when many factors change simultaneously. Uneven distribution of maternal-to-fetal blood flows tends to favor fetal water acquisition.

Cell Membrane Permeability↗

Survival in the fetal rabbit exposed to intermittent hypoxia.

To investigate the time course and mechanisms of fetal O2 deprivation, we exposed 93 near-term, pregnant rabbits and their fetuses in utero to intermittent hypoxia. We administered a gas mixture containing 3, 4, 5 or 6 per cent O2 in N2 to a rabbit for 0.5, 1, 2, or 3 minutes, alternately with a recovery period of air breathing of 0.5, 1, 2, or 3 minutes. A given cyclical pattern was continued for 2 hours and fetal survival recorded 1 hour thereafter. Fetal survival decreased significantly at lower O2 levels, longer durations of exposure, and shorter durations of recovery intervals between exposures. Chances for survival were significantly greater among fetuses located at either end of the uterine horn.

Animals↗