Specificity of a placental factor inhibiting breathing in fetal sheep

1996 ◽  
Vol 8 (3) ◽  
pp. 423 ◽  
Author(s):  
RE Alvaro ◽  
V Rehan ◽  
Almeida V de ◽  
Z Haider ◽  
M Robertson ◽  
...  
Keyword(s):  
High Voltage ◽  
Low Voltage ◽  
Fetal Liver ◽  
Fetal Life ◽  
Krebs Solution ◽  
Fetal Sheep ◽  
Electrocortical Activity ◽  
Fetal Breathing ◽  
Pregnant Ewe ◽  
Placental Extract

We have found previously that the infusion of a placental extract inhibits breathing induced by 100% O2 plus umbilical cord occlusion in the fetal sheep, suggesting that a placental factor is responsible for the inhibition of fetal breathing. To test whether this factor is specific to the placenta and whether it also inhibits spontaneous fetal breathing (occurring in the absence of cord occlusion), we administered extracts from the placenta, muscle and liver of the pregnant ewe, extracts of fetal liver, and Krebs solution to 16 chronically instrumented fetal sheep at 135 +/- 5 days of gestation. Infusions were made during low-voltage electrocortical activity, 5 to 15 min after a switch from high voltage, when breathing was well established. Within 90 s of the infusion of the placental extract in the carotid artery of the fetus, breathing decreased in 79% (33/42) of the experiments and was completely abolished in 71% (30/42) of them (P < 0.0001 compared with the other infusates). No apnoeas were observed with the Krebs solution (0/19) and the maternal muscle (0/20). Extracts of maternal and fetal liver abolished breathing in only 17% (4/23) and 21% (6/29) of the experiments respectively (NS compared with Krebs solution). There were no significant changes in blood gas tensions, pH, blood pressure and heart rate associated with the infusion of the extracts. The electrocortical activity (ECoG) switched from low to high voltage in 50% of the experiments using placental extract compared with 0% with Krebs solution and maternal muscle, and with 9% and 17% with maternal and fetal liver respectively (P < 0.005). Breathing output (integral of EMGdi x f) during and after the infusions significantly decreased only with the placental extract. These findings indicate the presence of a factor produced by the placenta which inhibits fetal breathing and may be responsible for the normal inhibition of breathing observed in fetal life.

Bladder contractions and micturition in fetal sheep: their relation to behavioral states

1989 ◽  
Vol 257 (6) ◽  
pp. R1526-R1532 ◽  
Author(s):  
M. E. Wlodek ◽  
G. D. Thorburn ◽  
R. Harding
Keyword(s):  
High Voltage ◽  
Low Voltage ◽  
Control Period ◽  
In Utero ◽  
Fetal Sheep ◽  
Electrocortical Activity ◽  
The Mean ◽  
Behavioral States ◽  
Mean Time ◽  
The Brain

Fetal bladder contractions, indicative of micturition (voiding), and behavioral states were monitored in unanesthetized fetal sheep in utero during the last third of gestation. Fetal voids began during low-voltage electrocortical activity (LV ECoG) at a greater frequency (91.4 +/- 1.0%) than expected (57.2%) and began during high-voltage electrocortical activity (HV ECoG) with a lower frequency (8.7 +/- 1.0%) than expected (42.8%). Fetal voids began significantly sooner after the onset of LV ECoG (5.84 +/- 0.13 min) than after the onset of HV ECoG (10.88 +/- 0.04 min). Electroocular and nuchal muscle activities were associated with 96.2 and 66.0% of the voids, respectively, but there was no significant association between fetal voiding and swallowing episodes. Abolition of spontaneous voiding, by urine drainage (24 h), caused no significant differences, relative to a 24-h control period, in the duration or number of episodes of LV or HV ECoG or percentage of time spent in these states. Also, induction of voiding by infusing saline into the bladder did not significantly alter the time to the next change of ECoG state. However, the mean time to the next void and the mean volume of saline infused into the bladder to induce voiding tended to be less during LV ECoG than HV ECoG, although not significantly less. Our data show that most spontaneous voids in the fetus begin during LV ECoG, suggesting that voiding is regulated by descending information from the brain. Furthermore, these experiments demonstrate that fetal bladder contractions and voiding, either spontaneous or induced, do not influence the normal cycling of fetal ECoG states.

Preliminary characterization of a placental factor inhibiting breathing in fetal sheep

1997 ◽  
Vol 9 (6) ◽  
pp. 641 ◽  
Author(s):  
Ruben E. Alvaro ◽  
May Robertson ◽  
Saad Al-Saedi ◽  
Robert P. Lemke ◽  
Don B. Cates ◽  
...  
Keyword(s):  
Proteinase K ◽  
Krebs Solution ◽  
Fetal Sheep ◽  
Dependent Effect ◽  
Ion Exchange Column ◽  
Fetal Breathing ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Placental Extract

Previous studies have revealed a placental extract that inhibits breathing in fetal sheep. In the present study of 29 chronically instrumented sheep at 132±1 days of gestation, infusion of the 1-10 kDa extract inhibited breathing in 76% of the experiments whereas Krebs’ solution inhibited it in 24%. It retained this activity after 6 months of freezing, after lyophilization, and upon lowering the pH during purication from 8·0 to 4·0, but it inhibited breathing in only 35% when the pH was lowered to 2·0. A signicant dose-dependent effect was observed from a 16-fold dilution to a 4-fold concentration. Treatment of the extract with proteinase K or boiling reduced the activity to 30% or 26% inhibition, respectively. The activity was not adsorbed to an ion-exchange column at pH 7·0 or 8· 0, but it was at pH 9· 0 and it eluted with increasing NaCl concentrations. On a polyacrylamide gel the activity was eluted at a Kav of 0· 66 (82% inhibition), corresponding to between 2·5 and 4·5 kDa. These ndings suggest that a peptide produced by the placenta, with a molecular mass between 2· 5 and 4·5 kDa, inhibits fetal breathing.

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.

Effects of various concentrations of O2 and umbilical cord occlusion on fetal breathing and behavior

1990 ◽  
Vol 68 (4) ◽  
pp. 1597-1604 ◽  
Author(s):  
R. J. Baier ◽  
S. U. Hasan ◽  
D. B. Cates ◽  
D. Hooper ◽  
B. Nowaczyk ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
High Voltage ◽  
Airway Pressure ◽  
Low Voltage ◽  
Fetal Lung ◽  
Mean Airway Pressure ◽  
Fetal Sheep ◽  
Arterial Pco2 ◽  
Fetal Breathing ◽  
And Behavior

To test the hypothesis that continuous fetal breathing could be induced by hyperoxemia alone or by hyperoxemia and umbilical cord occlusion, even in the absence of a rise in arterial PCO2 (PaCO2), we studied 18 chronically instrumented fetal sheep on 34 occasions using our window model (18). After a resting cycle (1 low-voltage followed by 1 high-voltage electrocortical activity epoch), the fetal lung was distended via an endotracheal tube using mean airway pressure of approximately cmH2O. Inspired N2, 17% O2, and 100% O2 were given to the fetus during one cycle each. While 100% O2 was given, the umbilical cord was occluded (balloon cuff).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of meclofenamate on breathing movements in fetal sheep before delivery

1988 ◽  
Vol 64 (2) ◽  
pp. 759-766 ◽  
Author(s):  
L. D. Wallen ◽  
D. T. Murai ◽  
R. I. Clyman ◽  
C. H. Lee ◽  
F. E. Mauray ◽  
...  
Keyword(s):  
Low Voltage ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Electrocortical Activity ◽  
Fetal Plasma ◽  
Prostaglandin Synthase ◽  
Fetal Breathing ◽  
Fetal Breathing Movements ◽  
Synthase Inhibitor ◽  
Control Infusion

There is evidence that prostaglandins (PG), specifically PGE2, participate in the regulation of fetal breathing movements (FBM). During late gestation, when FBM occur intermittently and primarily during low-voltage electrocortical activity, the concentration of PGE2 in fetal plasma ([PGE2]) is high. During the days before delivery [PGE2] increases and FBM decrease. To determine whether the increase in [PGE2] is responsible for the concurrent decrease in FBM, we infused the prostaglandin synthase inhibitor, meclofenamate (0.7 mg.kg-1.h-1), into eight fetal sheep continuously for 5-–13 days before delivery; five control fetuses received a continuous infusion of the solvent for 5–11 days before delivery. Compared with control infusion, meclofenamate caused a significant decrease in [PGE 2] until the day of delivery and a significant increase in FBM [overall and during high-voltage electrocortical activity (HVA)] until 2 days before delivery. Although there were significant correlations between [PGE2] and FBM (overall and during HVA), both groups showed similar decreases in FBM during the 2 days before delivery. We conclude that the decrease in FBM before delivery is not dependent on the concurrent increase in [PGE2].

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.

Metabolic and cardiorespiratory responses to hypoxia in fetal sheep: adenosine receptor blockade

1999 ◽  
Vol 276 (6) ◽  
pp. R1805-R1811 ◽  
Author(s):  
Andrew Chau ◽  
Brian J. Koos
Keyword(s):  
Adenosine Receptors ◽  
Low Voltage ◽  
Specific Inhibitor ◽  
Cardiovascular Responses ◽  
Inhibitory Effects ◽  
Fetal Sheep ◽  
Fetal Breathing ◽  
Phasic Rem Sleep ◽  
Transient Bradycardia

8-Phenyltheophylline (PT), a potent and specific inhibitor of adenosine receptors, was infused intra-arterially into unanesthetized fetal sheep to determine the role of adenosine in hypoxic inhibition of fetal breathing. PT in normoxic fetuses increased heart rate and the incidence of low-voltage electrocortical activity, rapid eye movements (REM), and breathing. Mean breath amplitude increased by 44%. Hypoxia (preductal arterial[Formula: see text] = 14 Torr) induced a metabolic acidemia, a transient bradycardia, and hypertension while virtually eliminating REM and breathing. PT administration during hypoxia enhanced the metabolic acidemia, blocked the bradycardia and hypertension, increased the incidence of REM and breathing, and elevated mean breath amplitude. The results indicate that 1) adenosine is involved in fetal glycolytic and cardiovascular responses to hypoxia, 2) activation of central adenosine receptors mediates about one-half the inhibitory effects of hypoxia on REM and breathing, and 3) the depression of breathing may critically depend on a hypoxia-induced reduction in phasic REM sleep.

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 breathing, sleep state, and cardiovascular responses to graded hypoxia in sheep

1987 ◽  
Vol 62 (3) ◽  
pp. 1033-1039 ◽  
Author(s):  
B. J. Koos ◽  
H. Sameshima ◽  
G. G. Power
Keyword(s):  
Low Voltage ◽  
Cardiovascular Responses ◽  
Severe Hypoxia ◽  
Sleep State ◽  
Fetal Sheep ◽  
Fetal Bradycardia ◽  
O2 Concentration ◽  
Fetal Breathing ◽  
The Mean ◽  
Mild Hypoxia

Graded isocapnic hypoxemia was produced in unanesthetized fetal sheep by varying the inspired O2 concentration (21, 12, 10.5, and 9%) of the ewe. This produced corresponding mean preductal arterial O2 tension (PaO2) values of 25.2 +/- 1.1 (control), 20.1 +/- 1.0 (mild hypoxia), 17.8 +/- 0.9 (moderate hypoxia), and 16.8 +/- 1.4 Torr (severe hypoxia). These were associated with mean arterial O2 contents (CaO2) of 7.18 +/- 0.44, 5.19 +/- 0.34, 4.24 +/- 0.33, and 3.27 +/- 0.20 ml/dl, respectively. The most severe hypoxia was associated with metabolic acidosis and fetal bradycardia. Hypoxia did not reduce significantly the incidence of low-voltage electrocortical activity. The incidence of breathing and rapid eye movements was not affected by mild hypoxia; however, the incidence of both was significantly reduced during moderate and severe hypoxia. It is concluded that 1) acute reductions in the mean PaO2 of 5.9 +/- 0.6 Torr and CaO2 of 2.00 +/- 0.23 ml/dl are critical in that greater reductions inhibit fetal eye and breathing activity and 2) hypoxia probably inhibits eye and breathing movements by altering sleep state.

Adenosine A1 and A2A receptors modulate sleep state and breathing in fetal sheep

2001 ◽  
Vol 91 (1) ◽  
pp. 343-350 ◽  
Author(s):  
Brian J. Koos ◽  
Takatsugu Maeda ◽  
Calvin Jan
Keyword(s):  
Low Voltage ◽  
Receptor Subtype ◽  
Respiratory Drive ◽  
Inhibitory Effects ◽  
Sleep State ◽  
Arterial Infusion ◽  
Fetal Sheep ◽  
A2a Receptors ◽  
Fetal Breathing ◽  
Adenosine A1

This study was designed to determine the adenosine (Ado) receptor subtype that mediates the depressant effects of Ado on fetal breathing and rapid eye movements (REM). In chronically catheterized fetal sheep (>0.8 term), intra-arterial infusion of N 6-cyclopentyladenosine (CPA), an Ado A1-receptor agonist, increased the incidence of high-voltage electrocortical (ECoG) activity while virtually abolishing low-voltage activity, REM, and breathing. These effects were blocked by 9-cyclopentyl-1,3-dipropylxanthine (DPCPX), an Ado A1-receptor antagonist. Infusion of DPCPX alone increased breath amplitude but had no significant effect on inspiratory duration, breath interval, incidence of REM, or incidence of low-voltage activity. Ado A2A-receptor blockade with ZM-241385 increased the incidence of low-voltage ECoG activity, REM, and breathing but had no effect on breath amplitude or respiratory cycle. Both DPCPX and ZM-241385 eliminated the inhibitory effects of Ado on REM and breathing. We conclude that 1) Ado A1receptors tonically inhibit fetal respiratory drive, 2) Ado A2A receptors tonically inhibit REM-like behavioral state, and 3) both Ado A1 and A2A receptors mediate the depressant effects of Ado on REM and breathing.

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