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

1994 ◽  
Vol 77 (6) ◽  
pp. 2734-2739 ◽  
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.

Behavioral activity during prolonged hypoxemia in fetal sheep

1988 ◽  
Vol 65 (6) ◽  
pp. 2420-2426 ◽  
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.

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

1992 ◽  
Vol 4 (2) ◽  
pp. 135 ◽  
Author(s):  
D Walker ◽  
A Bird ◽  
T Flora ◽  
B O'Sullivan
Keyword(s):  
Fetal Brain ◽  
Blood Gases ◽  
Maternal Blood ◽  
Tribulus Terrestris ◽  
Functional Development ◽  
Fetal Breathing ◽  
Fetal Breathing Movements ◽  
Poor Nutrition ◽  
Arterial Po2 ◽  
Length Of Gestation

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.

Effect of intermittent umbilical cord occlusion on fetal respiratory activity and brain adenosine in late-gestation sheep

2002 ◽  
Vol 14 (1) ◽  
pp. 35 ◽  
Author(s):  
Carole S. Watson ◽  
Rachel Schaefer ◽  
Susan E. White ◽  
Jacobus H. Homan ◽  
Laurence Fraher ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Fetal Brain ◽  
Extracellular Fluid ◽  
Inhibitory Effect ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Arterial Ph ◽  
Tracheal Pressure ◽  
Ovine Fetal ◽  
Arterial Po2

It was hypothesized that intermittent umbilical cord occlusion (UCO) would inhibit ovine fetal breathing movements (FBM) in association with increased cerebral adenosine levels. To test this hypothesis, on two successive days during late gestation (133–134 days; term = 146 days), microdialysis samples were collected from the brains of 10 chronically instrumented fetal sheep during 2-h periods of complete UCO induced every 30 min (Day 1: 2-min UCOs; Day 2: 4-min UCOs). Control fetuses (n = 10) underwent no UCO. Tracheal pressure was measured throughout. This regimen resulted in a decrease in fetal arterial PO2 (PaO2) during each UCO to 7.3 0.8 mmHg (P<0.01; Day 1) and 8.4 1.1 mmHg (P<0.01; Day 2). Throughout each UCO period, fetal arterial pH (pHa) decreased to 7.28 0.02 (P<0.01; Day 1) and 7.11 0.07 (P<0.01; Day 2). The hourly incidence of FBM decreased significantly only on Day 2, from 38.6 4.1% to 4.1 1.6% (P<0.01). The frequency of deep isolated inspiratory efforts increased from 4.7 2.0 h–1 to 17.6 6.1 h–1 (P<0.05; Day 1) and from 2.2 0.9 h–1 to 33.6 4 h–1 (P<0.01; Day 2). The amplitude of both FBM and deep isolated inspiratory efforts increased during the UCO periods on both days. The concentration of cerebral extracellular fluid (ECF) adenosine during UCO increased by 219 215% (P<0.05; Day 1) and 172 107% (P<0.05; Day 2) over the baseline periods. In conclusion, the severity of the inhibitory effect of repeated UCO on FBM depends, in part, on the length of the occlusions. The inhibition of FBM during intermittent UCO may be mediated by the increase in ECF adenosine in the fetal brain. Furthermore, FBM and deep isolated inspiratory efforts appear to be regulated by different mechanisms.

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

1994 ◽  
Vol 76 (4) ◽  
pp. 1476-1480 ◽  
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.

Denervation of peripheral chemoreceptors decreases breathing movements in fetal sheep

1985 ◽  
Vol 59 (2) ◽  
pp. 575-579 ◽  
Author(s):  
D. T. Murai ◽  
C. C. Lee ◽  
L. D. Wallen ◽  
J. A. Kitterman
Keyword(s):  
Low Voltage ◽  
Fetal Life ◽  
Fetal Sheep ◽  
Peripheral Chemoreceptors ◽  
Arterial Blood ◽  
Several Variables ◽  
Arterial Ph ◽  
Fetal Breathing ◽  
Fetal Breathing Movements

The role of the peripheral chemoreceptors in the control of fetal breathing movements has not been fully defined. To determine whether denervation of the peripheral chemoreceptors affects fetal breathing movements, we studied 14 chronically catheterized fetal sheep from 120 to 138 days of gestation. In seven fetuses the chemoreceptors were denervated by bilateral section of the vagus and carotid sinus nerves; in seven others, sham operations were performed. We compared several variables during two study periods: 0–5 and 6–13 days after operation. In the denervated fetuses there were significant decreases in the incidence and amplitude of fetal breathing movements during both study periods. There were no differences between the two groups in incidence of low-voltage electrocortical activity, arterial pH and blood gas tensions, fetal heart rate, mean arterial blood pressure, or duration of survival after operation or birth weight. We conclude that denervation of the peripheral chemoreceptors decreases fetal breathing movements. These results indicate that the peripheral chemoreceptors are active during fetal life and participate in the control of fetal breathing movements.

Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep

1990 ◽  
Vol 69 (1) ◽  
pp. 136-140 ◽  
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.

Thalamic Locus Mediates Hypoxic Inhibition of Breathing in Fetal Sheep

1998 ◽  
Vol 79 (5) ◽  
pp. 2383-2393 ◽  
Author(s):  
Brian J. Koos ◽  
Andrew Chau ◽  
Masahiko Matsuura ◽  
Oscar Punla ◽  
Lawrence Kruger
Keyword(s):  
Brain Stem ◽  
Ibotenic Acid ◽  
Nuclear Region ◽  
Fetal Sheep ◽  
Nuclear Complex ◽  
Fetal Breathing ◽  
The Brain

Koos, Brian J., Andrew Chau, Masahiko Matsuura, Oscar Punla, and Lawrence Kruger. Thalamic locus mediates hypoxic inhibition of breathing in fetal sheep. J. Neurophysiol. 79: 2383–2393, 1998. The effects of lesions rostral to the brain stem on breathing responses to hypoxia were determined in chronically catheterized fetal sheep (>0.8 term). These studies were designed to test the hypothesis that the diencephalon is involved in hypoxic inhibition of fetal breathing. As in normal fetuses, hypoxia inhibited breathing with transection rostral to the thalamus or transection resulting in virtual destruction of the thalamus but sparing most of the parafascicular nuclear complex. Neuronal lesions were produced in the fetal diencephalon by injecting ibotenic acid through cannulas implanted in the brain. Hypoxic inhibition of breathing was abolished when the lesions encompassed the parafascicular nuclear complex but was retained when the lesions spared the parafascicular nuclear region or when the vehicle alone was injected. A new locus has been identified immediately rostral to the midbrain, which is crucial to hypoxic inhibition of fetal breathing. This thalamic sector involves the parafascicular nuclear complex and may link central O2-sensing cells to motoneurons that inhibit breathing.

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

1990 ◽  
Vol 68 (2) ◽  
pp. 489-495 ◽  
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.

Fetal swallowing: response to graded maternal hypoxemia

1991 ◽  
Vol 71 (5) ◽  
pp. 1856-1861 ◽  
Author(s):  
D. J. Sherman ◽  
M. G. Ross ◽  
L. Day ◽  
J. Humme ◽  
M. G. Ervin
Keyword(s):  
Flow Measurement ◽  
Plasma Osmolality ◽  
Fetal Plasma ◽  
Percent Time ◽  
Arterial Ph ◽  
Fetal Breathing ◽  
Computer Based ◽  
Plasma Arginine ◽  
Arterial Po2 ◽  
Fluid Flow Measurement

A computer-based system, incorporating electromyography (EMG) and esophageal fluid flow measurement, was used to determine fetal breathing and swallowing responses to graded maternal hypoxemia. Five chronically prepared ewes with singleton fetuses at a gestational age of 130 +/- 2 (SE) days were subjected to successive 30-min periods of mild and moderate hypoxemia (inspired O2 fraction = 0.16 and 0.13, respectively). Mild and moderate maternal hypoxemia evoked significant reductions in fetal arterial PO2 (21 +/- 1 to 17 +/- 1 and 13 +/- 1 Torr, respectively), while fetal arterial pH, hematocrit, plasma osmolality, heart rate, and mean blood pressure did not change. Moderate hypoxemia was associated with significant increases in fetal plasma arginine vasopressin and renin activity and significant reductions from basal values in percent time breathing (53 +/- 4 to 25 +/- 12%), percent time swallowing (11.5 +/- 3.1 to 1.3 +/- 0.7%), and volume swallowed (21.3 +/- 2.1 to 4.8 +/- 2.7 ml/30 min). Fetal swallowing activity was better correlated with arterial PO2 (r = 0.8) than breathing activity (r = 0.45). We conclude that fetal swallowing is suppressed during mild and moderate hypoxemia. It is suggested that several sites and/or mechanisms may account for the hypoxemic inhibition of fetal activities.

Rebound increase in fetal breathing movements after 24-h prostaglandin E2 infusion in fetal sheep

1996 ◽  
Vol 80 (1) ◽  
pp. 166-175 ◽  
Author(s):  
S. A. Hollingworth ◽  
S. A. Jones ◽  
S. L. Adamson
Keyword(s):  
Prostaglandin E2 ◽  
Plasma Concentrations ◽  
Treated Group ◽  
High Plasma ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Pge2 Concentration ◽  
Fetal Breathing ◽  
Fetal Breathing Movements ◽  
Rebound Increase

We investigated the hypothesis that the precipitous decrease in prostaglandin E2 (PGE2), a potent inhibitor of fetal breathing, from high plasma concentrations during labor causes a rebound stimulation of breathing without newborn concentrations falling below prelabor fetal values. Fetal plasma PGE2 concentration was gradually increased from 384 +/- 82 (SE) pg/ml in 2-h steps [0 (baseline), 1.5, 3, and 6 micrograms/min] to labor levels (1,230 +/- 381 pg/ml at 6 micrograms/min) and then was maintained for 24 h (n = 9). PGE2 at 1.5 micrograms/min significantly decreased breathing incidence [from 42 +/- 4 (baseline) to 14 +/- 4%] and breath amplitude (from 2.1 +/- 0.5 to 1.5 +/- 0.2 arbitrary units) and increased breath-to-breath interval (from 1.16 +/- 0.07 to 1.56 +/- 0.06 s). No further dose-related changes were observed. During the first 2 h after PGE2 infusion was stopped, PGE2 concentration returned to basal (352 +/- 64 pg/ml) but breathing incidence and amplitude were significantly higher (74 +/- 8% and 2.4 +/- 0.3 arbitrary units, respectively) and breath-to-breath interval was significantly lower (0.95 +/- 0.10 s) than were basal levels. Changes arose within approximately 15 min and were maintained for at least 4 h. Breathing did not change significantly in the saline-treated group (n = 7). Results suggest that the rapid decrease in plasma PGE2 concentration at birth promotes the onset of breathing.

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