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Biomedical subjects

R A Brace

Publications and source records attributed to R A Brace.

At least 37 records · Page 2Linked to original sources
PubMed1996

Changes in left thoracic duct lymph flow during progressive anemia in the ovine fetus.

OBJECTIVE: The purpose of this study was to evaluate the extent to which increased lymph flow can return fluid and protein to the circulation in the chronically anemic fetus. STUDY DESIGN: Thoracic duct lymph flow rate over a range of outflow pressures was measured in 8 near-term fetal sheep 4 to 5 days after surgery and daily thereafter for 5 days. After each day's study 60 to 150 ml of blood was withdrawn at a rate of 1 ml per minute. Regression analysis was used to establish the lymph flow function curve. Lymph and plasma protein concentrations and lymph flow rate were compared by analysis of variance for repeated measures. RESULTS: As the hematocrit was reduced from 34.6% +/- 1.3% (mean +/- SE) to 14.4% +/- 1.0%, thoracic duct lymph flow increased from 0.12 +/- 0.01 to 0.28 +/- 0.02 ml/min/kg. Plasma total protein concentration did not change, lymph protein concentration fell (2.6 +/- 0.1 to 2.4 +/- 0.1 gm/dl), and the difference between plasma and lymph protein concentrations increased (1.04 +/- 0.05 to 1.34 +/- 0.10 gm/dl). Protein returned to the circulation increased from 11.5 +/- 0.3 to 23.7 +/- 1.5 mg per minute. Central venous pressure did not change and remained less than the breakpoint pressure. Although the plateau lymph flow rate increased, neither the breakpoint or stopflow pressures of the lymph flow function curve were altered. CONCLUSIONS: Fetal lymph flow and thereby capillary filtration increased progressively as anemia became more severe. The increase in lymph flow did not appear to be limited by outflow pressure. By returning protein to the circulation, an increase in thoracic duct lymph flow helped to limit expansion of extravascular fluid volume during chronic fetal anemia.

Anemia↗
PubMed1995

Vascular endothelial growth factor gene expression in ovine placenta and fetal membranes.

OBJECTIVE: The purpose of this study was to explore the gene expression of vascular endothelial growth factor (VEGF) in placental cotyledon, chorion, and amnion of the ovine fetus. STUDY DESIGN: Time-dated pregnant sheep with singleton or twin fetuses at a gestational age ranging from 100 to 140 days were used for the study. Placental cotyledonary, chorionic, and amniotic tissues were collected and processed for messenger ribonucleic acid analysis by Northern blotting and reverse transcription-polymerase chain reaction. RESULTS: By use of a phosphorus 32-labeled human VEGF complementary deoxyribonucleic acid probe, a prominent VEGF messenger ribonucleic acid transcript of 3.7 kb was detected in the cotyledon, chorion, and amnion. A minor band of 1.7 kb was also found but only in the cotyledon and chorion. The abundance of messenger ribonucleic acid encoding VEGF was highest (p < 0.001) in the cotyledon and lowest in the amnion. In these tissues polymerase chain reaction-amplified products corresponding to VEGF121, VEGF165, VEGF189, and VEGF206 were identified by ethidium bromide. In addition, a polymerase chain reaction fragment corresponding to VEGF145 was observed. These fragments produced specific hybridization signals with the human VEGF radioactive probe where the intensity of the signal was strongest for VEGF165 and weakest for VEGF189. CONCLUSIONS: VEGF gene expression was detected in the cotyledon, chorion, and amnion of the near-term ovine fetus. These findings suggest that vascular endothelial growth factor may play a role in the induction of angiogenesis and promotion of permeability in the microvessels that perfuse the placental and fetal membranes.

Animals↗
PubMed1995

Potential route for fetal therapy: intramembranous absorption of intraamniotically injected furosemide.

OBJECTIVE: Our purpose was to determine whether intraamniotically injected furosemide could be absorbed directly into fetal circulation by the ovine intramembranous pathway. STUDY DESIGN: Nine chronically catheterized fetal sheep, five with an intact and four with a surgically ligated esophagus, were studied for 7 hours on 2 consecutive days. Day 1 was a control day in which the fetal parameters of arterial, venous, and amniotic fluid pressures; heart rate; and urine flow were measured continuously. Fetal and maternal blood, amniotic fluid, and fetal urine were sampled for osmolality, electrolytes, blood gases, and pH twice during the first hour and hourly thereafter. On day 2, 15 mg of furosemide was injected into the amniotic cavity after 1 hour and fetuses were monitored in the same fashion as on the control day. RESULTS: On day 2, both intact and ligated fetuses demonstrated a rapid and prolonged increase in urine flow (p < 0.01) compared with control day fetuses. Esophageal ligation decreased, but did not eliminate, the diuresis. Free water clearance increased equally (p < 0.05) in both groups compared with control fetuses. Sodium and chloride excretion increased significantly in intact (sodium 591% +/- 220% and chloride 763% +/- 295%) and ligated fetuses (sodium 234% +/- 70% and chloride 409% +/- 74%) compared with control fetuses. CONCLUSIONS: Diuresis after esophageal ligation demonstrates that furosemide is absorbed by the ovine intramembranous pathway.

Absorption↗
PubMed1995

Thoracic duct lymph flow responses to hemorrhage in the ovine fetus.

Blood volume returns toward normal after hemorrhage much more rapidly in the fetus than in the adult due to a rapid entry of fluid and plasma proteins into the fetal circulation. One potential source of fetal fluids and plasma proteins is the lymphatic system, since basal lymph flow rate and interstitial protein concentration are high in the fetus. Furthermore, studies in adults suggest that lymph flow rate may increase following hemorrhage. To test the hypothesis that hemorrhage induces an increase in lymph flow in the fetus, 15 late-gestation ovine fetuses underwent left thoracic duct catheterization with low-resistance catheters and were studied 5 or more days after surgery at 134 +/- 1 (SE) days gestation. The protocol included three successive 30-min periods: control, hemorrhage, and recovery. During the first 5 min of the hemorrhagic period, 61 +/- 4 ml of fetal blood were removed. The blood was reinfused over the first 5 min of the recovery period. After the hemorrhage, fetal arterial pressure, venous pressure, and heart rate decreased (analysis of variance, P < 0.001). These variables significantly increased above basal levels following blood reinfusion. Fetal hematocrit (P < 0.001) and plasma protein concentration (P < 0.05) also decreased after the hemorrhage and returned to control values after the reinfusion. Fetal lymph flow rate was 0.55 +/- 0.06 (SE) ml/min before the hemorrhage and decreased by a maximum of 30.3 +/- 6.3% (P < 0.001) at 8 min after the end of the hemorrhage. Lymph flow rate was reduced by an average of 19.1 +/- 6.6% during the hemorrhagic period and returned to prehemorrhage levels following blood reinfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Endocrine responses of fetal sheep to prolonged hypoxemia with and without acidemia: relation to urine production.

Our aim was to examine the endocrine changes associated with alterations in fetal urine production during 24 h of hypoxemia induced by either reduced uterine blood flow (RUBF) or maternal N2 inhalation (N2). In contrast to RUBF, which caused a diuresis, N2 caused a transient antidiuresis; during both posthypoxemia periods (RUBF and N2), fetal urine production was increased. RUBF, but not N2, was associated with a transient acidemia. Fetal plasma arginine vasopressin (AVP) and atrial natriuretic factor (ANF) concentrations increased during RUBF and were inversely correlated to pH; there were no detectable AVP or ANF responses to N2. Fetal prostaglandin E2 (PGE2) increased during the hypoxemia and posthypoxemia periods induced by both methods, but RUBF caused the greater increase. AVP and PGE2 concentrations were positively correlated with urine production. Fetal arterial blood pressure increased during RUBF but not N2. During RUBF, the increases in AVP and PGE2 concentrations and/or fetal arterial blood pressure may have contributed to the diuresis. During N2, we suggest that low, but increased, levels of AVP may have caused the transient antidiuresis, whereas the diuresis observed during both posthypoxemia periods may have been mediated by elevated PGE2 concentrations and/or increased fetal arterial blood pressure.

Acids↗
PubMed1994

Swallowing of lung liquid and amniotic fluid by the ovine fetus under normoxic and hypoxic conditions.

OBJECTIVE: The lungs of the mammalian fetus secrete large volumes of fluid daily. The purpose of this study was to estimate the fraction of the lung liquid that is swallowed as it exits the fetal trachea versus that which enters the amniotic fluid under normoxic and hypoxic conditions. STUDY DESIGN: In chronically catheterized fetal sheep at 119 to 133 days' gestation the volume of fluid swallowed by the fetus was monitored five times per day for three consecutive 24-hour periods: control, hypoxia, and recovery. The Na+, K+, and Cl- concentrations of the swallowed fluid, lung liquid, and amniotic fluid were measured simultaneously. The fraction of the swallowed fluid that originated from the lungs or amniotic fluid was calculated from 24-hour average compositions and the assumption that the fetus swallowed only amniotic fluid and lung liquid. RESULTS: During the control, hypoxia, and recovery periods the fetuses swallowed 264 +/- 43 (SE), 92 +/- 23, and 271 +/- 24 ml/kg of fetal weight per day, respectively. As determined from Cl- concentrations, this swallowed fluid was composed of 17.7% +/- 2.7%, 24.8% +/- 5.8%, and 11.9% +/- 3.4% lung liquid, respectively, with the remainder being amniotic fluid. Throughout the three 24-hour observation periods there was an inverse relationship between the net 24-hour swallowed volume and the fraction of the swallowed fluid that originated from the lungs. Calculations based on Na+ concentrations yielded essentially the same results with slightly more scatter, whereas calculations based on K+ concentrations were unreliable. CONCLUSIONS: (1) Chloride concentrations provide the best of the three index values for a compositional analysis of fluids swallowed by the fetus. (2) Under normoxic conditions around 18% of swallowed fluid is derived from the fetal lungs. (3) On the basis of published fluid secretion rates for the fetal lung, an average of 50% of the liquid that exits the fetal trachea is swallowed and the rest mixes with the amniotic fluid.

Amniotic Fluid↗
PubMed1994

Indomethacin and arginine vasopressin interaction in the fetal kidney: a mechanism of oliguria.

OBJECTIVE: Indomethacin has been shown to cause fetal oliguria in humans and animals. This study was designed to test the hypothesis that indomethacin-induced fetal oliguria is mediated through the renal action of arginine vasopressin. STUDY DESIGN: Twenty-seven late-gestation (129 +/- 4 days [mean +/- SE]) chronically catheterized fetal sheep were studied. After a 1-hour control period fetal responses to indomethacin, 0.05 mg/kg given intravenously, followed by a 4-hour maintenance infusion (n = 9), were compared with an identical indomethacin infusion plus an arginine vasopressin V2-receptor antagonist (d[CH2]1(5), D-Phe2, Ile4,Arg8,Ala9)-VP (n = 8) or vehicle alone (n = 10). Fetal arterial and venous pressures, heart rate, and urinary flow were measured continuously. RESULTS: Fetal urinary flow rate (p < 0.0001) and free water clearance (p = 0.004) fell in response to indomethacin alone, but the addition of the arginine vasopressin V2-receptor antagonist blocked indomethacin's oliguric and free water effect. Urinary osmolality and sodium increased in both indomethacin and indomethacin+arginine vasopressin V2-receptor antagonist groups compared with vehicle (p < 0.05). Fetal arterial pressure increased in response to indomethacin, and the addition of the arginine vasopressin V2-receptor antagonist potentiated this response (p = 0.007). CONCLUSIONS: These results suggest that (1) fetal oliguria secondary to indomethacin is mediated through the stimulation of the renal arginine vasopressin V2-receptor and (2) prostaglandin synthesis inhibition may play a role in renal tubular sodium handling. In addition, the arginine vasopressin V2-receptor plays a role in ameliorating the hypertensive response to indomethacin. We speculate that indomethacin stimulates circulating arginine vasopressin levels and enhances peripheral arginine vasopressin effects in the fetus, resulting in oliguria and hypertension.

Animals↗
PubMed1994

Fetal vascular pressure responses to nonlabor uterine contractions: dependence on amniotic fluid volume in the ovine fetus.

OBJECTIVE: This investigation tested the hypothesis that elevations in fetal vascular pressures during nonlabor uterine contractions would be eliminated during polyhydramnios and augmented during oligohydramnios. STUDY DESIGN: Twenty-two chronically catheterized fetal sheep were divided into three groups: (1) control with normal amniotic fluid volume, (2) polyhydramnios produced by amnioinfusion, and (3) oligohydramnios produced by fluid drainage. Fetal arterial pressure, venous pressure, and amniotic fluid pressure were continuously recorded with on-line computer techniques. Amniotic fluid pressure was continuously subtracted from fetal arterial pressure and fetal venous pressure to correct to the fetal zero pressure reference. One minute averages were collected for 30 minutes centered around the nonlabor uterine contraction. RESULTS: Amniotic fluid pressure increased significantly during nonlabor uterine contractions in the control group. During polyhydramnios the amplitude and duration of the amniotic fluid pressure elevation were similar to those of controls (not significant). During oligohydramnios the duration of the uterine contractions was similar to that of both controls and polyhydramnios groups; however, the amplitude was less (p < 0.001). Fetal vascular pressures increased significantly during nonlabor uterine contractions in the control group (p < 0.001) but did not change significantly during nonlabor contractions in the polyhydramnios group. The contraction-induced elevations in fetal arterial pressure and fetal venous pressure in the oligohydramnios group were significantly greater than those in the control group (p < 0.001). CONCLUSION: This study shows that the fetal vascular pressure responses to nonlabor uterine contractions were modified significantly by increases or decreases in amniotic fluid volume. The fact that the fetal arterial pressure and fetal venous pressure responses were augmented during oligohydramnios and eliminated during polyhydramnios suggests that direct compression or a conformational change of the fetus may be the cause of the vascular pressure changes during nonlabor contractions.

Amniotic Fluid↗
PubMed1994

Blood volume response to drainage of left thoracic duct lymph in the ovine fetus.

Although it is known that left thoracic duct lymph flow rate in the ovine fetus is several times that in the adult relative to body weight, the role of the lymphatic system in maintaining fetal blood volume has not been explored. In the present study, the left thoracic lymph duct was drained without return to the fetal circulation in 10 chronically catheterized animals for 7 h. Four experiments in which the lymph was returned to the circulation served as control. During the 7-h drainage, the total volume drained was 174.4 +/- 19.6 ml. Thoracic duct lymph flow rate decreased gradually and averaged 22.2 +/- 3.4% (SE) below control at 6-7 h compared with a small increase in the control experiments (analysis of variance: P = 0.0013 comparing 2 groups). Fetal blood volume decreased (P < 0.0001) by 8.2 +/- 1.1% at 3 h because of a decrease in plasma volume with a further small decrease in blood volume to 9.7 +/- 0.9% below normal at 7 h. The decreases in blood volume at 1, 3, 5, and 7 h were 49.5, 40.2, 24.6, and 21.7%, respectively, of the volume of lymph that was drained. Fetal vascular pressures and heart rate did not change significantly. Although protein concentrations in plasma (-6.8 +/- 1.3%) and lymph (-7.5 +/- 2.1%) decreased, the lymph-to-plasma protein concentration ratio remained constant at 0.72 +/- 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Swallowing and urine flow responses of ovine fetuses to 24 h of hypoxia.

The aim of this study was to determine the effects of 24 h of hypoxia on fetal swallowing and urine flow rates. The study design included successive 24-h control, hypoxia, and recovery periods. To induce hypoxia, we infused nitrogen into the trachea of late-gestation pregnant sheep. During hypoxia, there were decreases in fetal arterial oxygen saturation [from 62.7 +/- 2.2 to 30.9 +/- 2.9% (SE)] and PO2 (from 21.1 +/- 1.0 to 14.1 +/- 0.9 mmHg) (n = 7). Fetal arterial pH decreased maximally by 0.04 +/- 0.01 at 6 h and returned to control thereafter. Fetal swallowing decreased from 13.4 +/- 2.1 to 0.6 +/- 0.2 ml.h-1.kg fetal wt-1 with the onset of hypoxia and gradually increased, but only to one-half control levels, during the last 12 h of hypoxia. Fetal urine flow gradually decreased from 9.6 +/- 1.6 ml.h-1.kg-1 to a minimum of 5.3 +/- 0.5 ml.h-1.kg-1 at 2-3 h of hypoxia and returned to control thereafter. During the first hour of the recovery period, fetal swallowing transiently increased to twice control levels before returning to control. This was followed by a delayed, transient increase in urine flow to 63% above control levels at 2-6 h after hypoxia. We conclude that the fetal swallowing and urine flow responses to prolonged hypoxia in the absence of acidemia are distinctly different from the initial inhibitory responses, in that swallowing partially and urine flow fully recovers from the initial suppression.

Animals↗
PubMed1993

Restoration of fetal red blood cells and plasma proteins after a moderately severe hemorrhage in the ovine fetus.

OBJECTIVE: We hypothesized that the fetus, in response to a moderately severe hemorrhage, would restore its plasma volume and red blood cells so that plasma volume would be returned to normal within 24 hours and red blood cell mass would be restored in 5 to 7 days. STUDY DESIGN: Time-dated pregnant sheep (five control and six hemorrhage, gestational age 124 +/- 1 [SE] days) were subjected to a 10-day protocol. Fetal blood volume, plasma volume, red blood cell mass, and plasma protein mass were measured on protocol days 1, 3, 4, 6, 8, and 10. Fetal plasma erythropoietin and plasma iron concentrations were measured daily. On protocol day 3 the hemorrhage animals underwent a 120 ml fetal hemorrhage over 2 hours. Statistical analysis was by three-factor analysis of variance. RESULTS: Control animals had a progressive increase in blood volume, plasma volume, plasma protein mass, and red blood cell mass throughout the 10-day protocol. The 2-hour hemorrhage removed 39.8% +/- 1.2% of the prehemorrhage blood volume. During the 7-day posthemorrhage recovery period fetal blood volume and red blood cell mass in the animals that were hemorrhaged expanded in parallel to, but remained below, that of the control animals. There was no difference in the expansion of fetal plasma volume or plasma protein mass between the two groups. After hemorrhage there was a nonsignificant increase in the fetal reticulocyte index in the animals undergoing hemorrhage. In response to the hemorrhage, erythropoietin levels increased and remained marginally elevated, whereas plasma iron levels decreased in the hemorrhaged animals relative to controls during the 7-day recovery period. CONCLUSIONS: The normal expansion of plasma volume and plasma protein mass that occurs with fetal growth was not altered by a large fetal blood loss. However, in spite of a transient increase in plasma erythropoietin levels the fetuses undergoing hemorrhage did not restore their red blood cell mass or blood volume. These observations suggest that the ovine fetus is able to withstand a significant loss of red blood cells, but fetal transfusion may be needed to restore fetal red blood cell mass after a moderate-to-severe fetal hemorrhage.

Animals↗
PubMed1993

Maximal lymph flow in the ovine fetus.

OBJECTIVE: This study was designed to determine the maximal left thoracic duct lymph flow rate in late-gestation ovine fetuses. STUDY DESIGN: Chronically catheterized sheep fetuses (n = 8) with indwelling left thoracic lymph duct and vascular catheters were studied > or = 5 days after surgery at 136 +/- 1 (SE) days' gestation. To increase lymph flow rate, 4 L of warm lactated Ringer's solution were infused intravenously into the fetus over 4 hours, because this causes mild edema as determined ultrasonographically. RESULTS: During a 1-hour preinfusion period lymph flow rate was 0.53 +/- 0.06 ml/min. During the infusion increases occurred in fetal arterial (7.6 +/- 1.0 mm Hg) and venous (2.4 +/- 0.3 mm Hg) pressures (p < 0.001). Lymph flow rate increased and reached a plateau after 1 hour at 339% +/- 30% of preinfusion values (p < 0.001). When the infusion was terminated, fetal arterial and venous pressures rapidly returned to preinfusion levels. Lymph flow rate gradually decreased during the first 30 minutes and stabilized at 97% +/- 17% above control during the subsequent 30 minutes. Analysis of lymph flow rate as a function of outflow pressure revealed that the increases in flow occurred because of an upward shift in the plateau flow rate with no change in the stop-flow pressure. CONCLUSIONS: (1) Fetal left thoracic duct lymph flow rate can increase significantly above basal values and therefore is an important safety factor against fetal edema formation. (2) The maximal lymph flow rate appears to be 3.4 times normal when venous pressure is elevated and two times normal when venous pressure is normal.

Animals↗
PubMed1993

Hemodynamic and fluid responses to furosemide infusion in the ovine fetus.

OBJECTIVES: The direct effects of furosemide infusion have not been systematically examined in the fetus. Our objective was to explore the hemodynamic and urinary responses to a 4-hour infusion of furosemide into fetal sheep. STUDY DESIGN: Furosemide (0, 1, 5, or 10 mg/hr) was infused into the fetal inferior vena cava for 4 hours in 15 chronically catheterized near-term sheep. RESULTS: Relative to vehicle infusion, furosemide produced dose-dependent increases in fetal arterial pressure (analysis of variance, p < 0.05 when comparing groups), fetal heart rate (p < 0.0001), urine flow (p < 0.0001), and urine osmolality, sodium, and chloride, concentrations (p < 0.0001). Concomitantly, there were dose-dependent decreases in fetoplacental blood volume, fetal plasma chloride (p < 0.0001) and fetal venous pressure (p < 0.05). The changes in urine flow rate and fetal arterial pressure were positively correlated (r = 0.46, p < 0.01), suggesting that the diuresis was mediated in part by fetal arterial pressure. The four-quadrant amniotic fluid index increased during the furosemide infusions but not during vehicle infusions (p = 0.022). CONCLUSIONS: Furosemide infusion caused a marked dose-dependent diuresis in the ovine fetus that appears to be partly mediated by increases in vascular pressure. Although amniotic fluid volume increases and fetal blood volume decreases, the reduction in blood volume was small compared with the urine volume excreted.

Amniotic Fluid↗
PubMed1993

Autonomic modulation of ovine fetal responses to atrial natriuretic factor infusion.

The aim of this study was to determine whether the autonomic nervous system modulates the cardiovascular, endocrine, and/or urinary responses to atrial natriuretic factor (ANF) infusion in the fetus. We infused ANF intravenously for 30 min into chronically catheterized, late-gestation sheep fetuses with autonomic blockade and compared the responses to those in autonomically intact fetuses. During the infusions, plasma ANF concentration increased similarly in the blocked and intact fetuses. Arterial pressure decreased by 2 mmHg in both groups, but the decrease occurred earlier in the blocked fetuses. Heart rate was significantly decreased by an average of 15 beats/min in the blocked compared with the intact fetuses. Plasma protein concentration decreased in the blocked fetuses compared with a rise in the intact fetuses. In the blocked fetuses, the restoration of blood volume to normal during the postinfusion period occurred earlier. In the blocked animals, low doses of ANF produced a diuresis, whereas high doses did not increase urine flow; the opposite responses occurred in the intact group. Plasma arginine vasopressin (AVP) concentration increased during the infusion only in the blocked animals. The fetal venous pressure, plasma renin activity, and norepinephrine responses were similar in both groups. These data suggest that the autonomic nervous system may play a role in modulating the fetal arterial pressure, heart rate, blood volume, plasma protein concentration, AVP, and urine flow responses to ANF. Thus the autonomic nervous system appears to significantly modulate multiple responses to ANF in the late-gestation ovine fetus.

Animals↗
PubMed1993

Amniotic fluid volume and normal flows to and from the amniotic cavity.

The regulation of amniotic fluid volume and composition remains largely unknown. Several difficult to study pathways exist for the formation (early transfer across fetal skin, fetal urine and lung fluid production) and removal (swallowing, transmembranous and intramembranous absorption) of amniotic fluid. It appears that flows across these pathways may work in concert the vast majority of the time because amniotic fluid volume is maintained within a normal range. When significant deviations occur from this normal range, especially in the mid trimester, significant perinatal morbidity and mortality incidence results.

Amnion↗
PubMed1992

A unique hypertonic response to hypotonic infusion in the pregnant ewe.

OBJECTIVE: The purpose of this study was to compare the responses of the maternal ewe to intravenous volume expansion with either sufficient lactated Ringer's solution to elevate maternal venous pressure or sufficient hypotonic fluid to reduce blood osmolality. STUDY DESIGN: Chronically catheterized pregnant sheep were intravenously infused over 4 hours with either commercial lactated Ringer's solution (5.55 +/- 0.50 L/hr, 255 mOsm/kg, mildly hypotonic) or diluted Ringer's solution (2.04 +/- 0.27 L/hr, 150 mOsm/kg, markedly hypotonic). Data were statistically analyzed with two- and three-factor analyses of variance and bivariate regression analysis. RESULTS: During the mildly hypotonic infusion (n = 8) the maternal blood osmolality changes were -5.1 +/- 1.2, +2.7 +/- 1.0 and +6.8 +/- 1.1 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. In four of the eight animals in this group profuse diarrhea developed. During the markedly hypotonic infusion (n = 11) the maternal blood osmolality changes were -9.9 +/- 1.1, -15.9 +/- 2.5, and -10.4 +/- 2.2 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. Although urine osmolalities were significantly less than the osmolality of the infusate in both groups, only during the mildly hypotonic infusion was there a net loss of free water by the kidneys. The renal free water loss, the venous pressure increase, and the blood osmolality decrease were not significantly different whether diarrhea did or did not develop. CONCLUSION: The infusion of large volumes of mildly hypotonic Ringer's solution to the pregnant ewe produces a paradoxic increase in maternal plasma osmolality as a result of the excretion of large volumes of free water by the kidneys, and if the venous pressure is increased more than about 6 mm Hg with this infusion, diarrhea develops in the animals.

Animals↗
PubMed1992

Indomethacin-induced urinary flow rate reduction in the ovine fetus is associated with reduced free water clearance and elevated plasma arginine vasopressin levels.

OBJECTIVE: The purpose of our study was to explore the urinary responses of the ovine fetus to indomethacin levels comparable with those used therapeutically in the human fetus. STUDY DESIGN: After a 1-hour control period, chronically catheterized ovine fetuses between 125 and 139 days of gestation were given an intravenous bolus of indomethacin (0.05 mg/kg estimated fetal weight) followed by a 0.0025 mg/kg/min continuous infusion for 5 hours. The experimental group (n = 9) was compared with a vehicle-only infusion group (n = 10). RESULTS: There was a sustained 55.7% +/- 9.5% (mean +/- SEM) decrease in urinary output by 2 hours of indomethacin infusion (p < 0.00001, analysis of variance). Urinary osmolality, potassium, and chloride concentrations underwent sustained increases during the infusion period (p < 0.005). Free water clearance decreased by 67.5% +/- 12.0% (p < 0.001). Fetal arterial pressure increased only transiently (p < 0.05), and increases in venous pressure (p = 0.013) and heart rate (p < 0.0001) were sustained. Fetal plasma arginine vasopressin concentration increased during indomethacin infusion (p < 0.05) and was correlated with the fall in urinary flow rate and free water clearance (p = 0.002). During vehicle infusion no significant changes were observed in any of the variables. CONCLUSIONS: Our data indicate that the fetus undergoes antidiuresis when exposed to low levels of indomethacin and that the observed antidiuresis is mediated by a decrease in free water clearance. The reduction in free water clearance may be mediated by increases in plasma arginine vasopressin concentrations.

Animals↗