Some effects of feeding Tribulus terrestris, Ipomoea lonchophylla and the seed of Abelmoschus ficulneus on fetal development and the outcome of pregnancy in sheep

Pregnant ewes and their fetuses were chronically catheterized using aseptic procedures under general anaesthesia, and the ewes were then fed either lucerne chaff alone, or lucerne mixed with dried plant material obtained from one of three forb species, Tribulus terrestris (caltrop), Abelmoschus ficulneus (native rosella) or Ipomoea lonchophylla (cowvine), from 103-112 days gestation until term. Ingestion of the forb material was not associated with changes in maternal blood gases, plasma glucose concentrations, or the length of gestation. However, ingestion of rosella seed was associated with a significantly greater fall of fetal arterial pO2 with advancing gestation, and ingestion of either rosella or cowvine was associated with significantly lower fetal mean arterial pressure at 127-131 days, compared with the Tribulus and lucerne groups. Also, the incidence of fetal breathing movements was significantly lower, and did not show a normal day-night variation, in each of the forb-fed groups compared with the lucerne-fed group. The results indicate that these forb plants may contain substances that affect the functional development of the fetal brain. Although ingestion of these plants did not appear to affect the outcome of pregnancy in this study, the possibility that these forbs have a greater impact in sheep populations with poor nutrition and in more extreme environmental conditions is discussed.

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Hypoxic inhibition of breathing in fetal sheep: relationship to brain adenosine concentrations

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.6.2734 ◽

1994 ◽

Vol 77 (6) ◽

pp. 2734-2739 ◽

Cited By ~ 44

Author(s):

B. J. Koos ◽

B. A. Mason ◽

O. Punla ◽

A. M. Adinolfi

Keyword(s):

Brain Stem ◽

Fetal Brain ◽

Normal Incidence ◽

Halothane Anesthesia ◽

Microdialysis Probe ◽

Fetal Sheep ◽

Arterial Ph ◽

Fetal Breathing ◽

Fetal Breathing Movements ◽

Arterial Po2

Because hypoxic inhibition of fetal breathing may be caused by a rise in central adenosine levels, the effects of O2 deficiency on fetal brain adenosine concentrations were determined at levels of hypoxia that inhibited fetal breathing. Under halothane anesthesia, the brains of fetal sheep (0.8 term) were implanted with guide cannulas exteriorized through a Silastic rubber window in the uterus and flank of the ewe. At least 4 days after surgery, a microdialysis probe was inserted into a cannula with the membrane tip placed in the rostral brain stem. During 1 h of isocapnic hypoxia, mean fetal arterial PO2 was reduced from 24.0 +/- 0.9 Torr (control) to 13 +/- 0.6 Torr and arterial pH fell progressively from 7.354 +/- 0.007 to 7.273 +/- 0.023. Hypoxia decreased the incidence of fetal breathing movements from 33 +/- 5.2 to 5 +/- 2.2 min/h, with a normal incidence (29 +/- 3.5 min/h) during the hour after arterial PO2 returned to control values. Adenosine concentrations in microdialysis perfusate under control conditions averaged approximately 35 nM, increased up to 2.3-fold during the hour of O2 deficiency, and fell toward control values when normoxia was restored. We conclude that fetal brain adenosine levels are increased at levels of O2 deficiency that inhibit fetal breathing, which are results consistent with a role for adenosine in hypoxic inhibition of fetal breathing.

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Effect of Changes in Maternal Blood Gases on Fetal Breathing Movements

Real Time Ultrasound in Perinatal Medicine - Contributions to Gynecology and Obstetrics ◽

10.1159/000402836 ◽

1979 ◽

pp. 88-91 ◽

Cited By ~ 5

Author(s):

H. K. Van Weering ◽

J. W. Wladimiroff ◽

P. J. Roodenburg

Keyword(s):

Blood Gases ◽

Maternal Blood ◽

Fetal Breathing ◽

Fetal Breathing Movements

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Fetal breathing, sleep state, and cardiovascular responses to adenosine in sheep

Journal of Applied Physiology ◽

10.1152/jappl.1990.68.2.489 ◽

1990 ◽

Vol 68 (2) ◽

pp. 489-495 ◽

Cited By ~ 50

Author(s):

B. J. Koos ◽

K. Matsuda

Keyword(s):

Eye Movements ◽

Low Voltage ◽

Blood Gases ◽

Hemoglobin Concentration ◽

Cardiovascular Responses ◽

Sleep State ◽

Fetal Sheep ◽

Adenosine Receptor Antagonist ◽

Fetal Breathing ◽

Arterial Po2

The possibility that adenosine mediates hypoxic inhibition of fetal breathing and eye movements was tested in nine chronically catheterized fetal sheep (0.8 term). Intracarotid infusion of adenosine (0.25 +/- 0.03 mg.min-1.kg-1) for 1 h to the fetus increased heart rate and hemoglobin concentration but did not significantly affect mean arterial pressure or blood gases. As with hypoxia, adenosine decreased the incidence of rapid eye movements by 55% and the incidence of breathing by 77% without significantly affecting the incidence of low-voltage electrocortical activity. However, with longer (9 h) administration, the incidence of breathing and eye movements returned to normal during the adenosine infusion. Intravenous infusion of theophylline, an adenosine receptor antagonist, prevented most of the reduction in the incidence of breathing and eye movements normally seen during severe hypoxia (delta arterial PO2 = -10 Torr). It is concluded that 1) adenosine likely depresses fetal breathing and eye movements during hypoxia and 2) downregulation of adenosine receptors may contribute to the adaptation of breathing and eye movements during prolonged hypoxia.

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Effect of mild hypocapnia on fetal breathing and behavior in unanesthetized normoxic fetal lambs

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.4.1476 ◽

1994 ◽

Vol 76 (4) ◽

pp. 1476-1480 ◽

Cited By ~ 11

Author(s):

I. M. Kuipers ◽

W. J. Maertzdorf ◽

D. S. De Jong ◽

M. A. Hanson ◽

C. E. Blanco

Keyword(s):

Low Voltage ◽

Blood Gases ◽

Electromyographic Activity ◽

Fetal Life ◽

Fetal Sheep ◽

Arterial Ph ◽

Fetal Breathing ◽

The Mean ◽

And Behavior ◽

Arterial Po2

We hypothesized that the level of arterial PCO2 (PaCO2) affects the incidence of fetal breathing movements and electrocorticographic (ECoG) states in chronically instrumented fetal sheep. Six fetuses of 128–132 days gestational age were instrumented for recording fetal behavior and for later connection to an extracorporeal membrane oxygenation (ECMO) system to change fetal blood gases. Before ECMO fetal arterial pH and blood gases were pH 7.40 +/- 0.01, PaCO2 42.9 +/- 1.5 Torr, and arterial PO2 (PaCO2) 19.2 +/- 1.7 Torr; during ECMO in normocapnia they were pH 7.37 +/- 0.01, PaCO2 46.1 +/- 0.7 Torr, and PaCO2 27.6 +/- 3.0 Torr; and during ECMO in mild hypocapnia they were pH 7.47 +/- 0.01, PaCO2 35.3 +/- 1.7 Torr, and PaCO2 26.6 +/- 1.7 Torr. The overall incidence of breathing movements, the incidence of breathing movements during low-voltage (LV) ECoG activity, and the mean duration of periods of breathing decreased significantly during hypocapnia. Fetal ECoG activity showed normal cycling during the periods of mild hypocapnia, and the mean duration of LV ECoG periods did not change. During mild hypocapnia, eye movements remained associated with LV ECoG activity and nuchal electromyographic activity remained associated with high-voltage ECoG activity. These results suggest that the presence of breathing movements in fetal life is not only dependent on the behavioral state but also on the level of fetal PaCO2.

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Effect of maternal hypoxemia on behavior in unanesthetized normoxic or mildly hyperoxic fetal lambs

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.6.2535 ◽

1994 ◽

Vol 76 (6) ◽

pp. 2535-2540 ◽

Cited By ~ 1

Author(s):

I. M. Kuipers ◽

W. J. Maertzdorf ◽

H. Keunen ◽

D. S. De Jong ◽

M. A. Hanson ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Eye Movements ◽

Electromyographic Activity ◽

Extra Corporeal Membrane Oxygenation ◽

Fetal Blood ◽

Fetal Breathing ◽

Fetal Breathing Movements ◽

Fetal Activity ◽

Arterial Po2

To determine whether hypoxemia inhibits fetal activity by substances from the mother or placenta, six fetal lambs were chronically instrumented at 128–132 days gestation for extra-corporeal membrane oxygenation (ECMO). Severe maternal hypoxemia (arterial PO2 decreased to 6.00 +/- 0.60 kPa) was produced while fetal arterial PO2 was maintained normoxic or mildly hyperoxic using ECMO. The incidences of fetal breathing movements were 34.8 +/- 3.1% (SE) during baseline before ECMO, 36.8 +/- 3.4% during baseline with ECMO, and 21.4 +/- 3.5% (P < 0.05 compared with baseline with ECMO) during maternal hypoxemia. The durations of periods of breathing were 9.8 +/- 1.2 min before ECMO, 9.3 +/- 1.1 min with ECMO, and 10.5 +/- 1.7 min (P = NS) during maternal hypoxemia. In 7 of 14 maternal hypoxemia experiments, breathing activity stopped too late (7–23 min) to be attributed to maternal hypoxemia. Fetal electrocorticographic activity (P = NS), nuchal electromyographic activity (P = NS), and eye movements were normal before ECMO, with ECMO, and during maternal hypoxemia. Fetal blood pressure and heart rate did not change. We conclude that the inhibition of fetal activity during maternal hypoxemia does not seem to be mediated by release of factors from the maternal side of the placenta or the ewe.

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The effect of maternal blood sugar levels on fetal breathing movements

Archives of Gynecology ◽

10.1007/bf02110680 ◽

1982 ◽

Vol 233 (1) ◽

pp. 63-65

Author(s):

A. Jakobovits ◽

E. Keller

Keyword(s):

Blood Sugar ◽

Maternal Blood ◽

Fetal Breathing ◽

Fetal Breathing Movements ◽

Sugar Levels

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Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.1.136 ◽

1990 ◽

Vol 69 (1) ◽

pp. 136-140 ◽

Cited By ~ 4

Author(s):

B. J. Koos ◽

K. Matsuda ◽

G. G. Power

Keyword(s):

Fetal Heart ◽

Fetal Brain ◽

Cardiovascular Responses ◽

Dependent Manner ◽

Brain Oxygenation ◽

Fetal Sheep ◽

Fetal Breathing ◽

Dose Dependent ◽

Arterial Po2 ◽

The Brain

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.

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Behavioral activity during prolonged hypoxemia in fetal sheep

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.6.2420 ◽

1988 ◽

Vol 65 (6) ◽

pp. 2420-2426 ◽

Cited By ~ 49

Author(s):

A. D. Bocking ◽

R. Gagnon ◽

K. M. Milne ◽

S. E. White

Keyword(s):

Blood Flow ◽

Eye Movements ◽

Normal Incidence ◽

Behavioral Activity ◽

Uterine Blood Flow ◽

Fetal Sheep ◽

Pregnant Sheep ◽

Fetal Breathing ◽

Fetal Breathing Movements ◽

Internal Iliac

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.

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Transfer of rhodamine-123 into the brain and cerebrospinal fluid of fetal, neonatal and adult rats

Fluids and Barriers of the CNS ◽

10.1186/s12987-021-00241-8 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Liam M. Koehn ◽

Katarzyna M. Dziegielewska ◽

Mark D. Habgood ◽

Yifan Huang ◽

Norman R. Saunders

Keyword(s):

Cerebrospinal Fluid ◽

Fetal Brain ◽

Maternal Blood ◽

Adult Brain ◽

Rhodamine 123 ◽

Patient Specific ◽

Adult Rats ◽

Blood Brain ◽

The Brain ◽

Brain Barriers

Abstract Background Adenosine triphosphate binding cassette transporters such as P-glycoprotein (PGP) play an important role in drug pharmacokinetics by actively effluxing their substrates at barrier interfaces, including the blood-brain, blood-cerebrospinal fluid (CSF) and placental barriers. For a molecule to access the brain during fetal stages it must bypass efflux transporters at both the placental barrier and brain barriers themselves. Following birth, placental protection is no longer present and brain barriers remain the major line of defense. Understanding developmental differences that exist in the transfer of PGP substrates into the brain is important for ensuring that medication regimes are safe and appropriate for all patients. Methods In the present study PGP substrate rhodamine-123 (R123) was injected intraperitoneally into E19 dams, postnatal (P4, P14) and adult rats. Naturally fluorescent properties of R123 were utilized to measure its concentration in blood-plasma, CSF and brain by spectrofluorimetry (Clariostar). Statistical differences in R123 transfer (concentration ratios between tissue and plasma ratios) were determined using Kruskal-Wallis tests with Dunn’s corrections. Results Following maternal injection the transfer of R123 across the E19 placenta from maternal blood to fetal blood was around 20 %. Of the R123 that reached fetal circulation 43 % transferred into brain and 38 % into CSF. The transfer of R123 from blood to brain and CSF was lower in postnatal pups and decreased with age (brain: 43 % at P4, 22 % at P14 and 9 % in adults; CSF: 8 % at P4, 8 % at P14 and 1 % in adults). Transfer from maternal blood across placental and brain barriers into fetal brain was approximately 9 %, similar to the transfer across adult blood-brain barriers (also 9 %). Following birth when placental protection was no longer present, transfer of R123 from blood into the newborn brain was significantly higher than into adult brain (3 fold, p < 0.05). Conclusions Administration of a PGP substrate to infant rats resulted in a higher transfer into the brain than equivalent doses at later stages of life or equivalent maternal doses during gestation. Toxicological testing of PGP substrate drugs should consider the possibility of these patient specific differences in safety analysis.

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