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.

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.

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 graded anemia in sheep

1987 ◽  
Vol 63 (4) ◽  
pp. 1463-1468 ◽  
Author(s):  
B. J. Koos ◽  
H. Sameshima ◽  
G. G. Power
Keyword(s):  
Eye Movements ◽  
Cardiovascular Responses ◽  
Severe Anemia ◽  
Sleep State ◽  
Fetal Sheep ◽  
Rapid Eye Movements ◽  
Mild Anemia ◽  
Arterial Blood ◽  
Moderate Anemia ◽  
Pressure Changes

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2–3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.

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.

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.

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.

Effects of hypercapnia and hypoxemia on fetal breathing after decortication

1986 ◽  
Vol 61 (3) ◽  
pp. 1071-1076 ◽  
Author(s):  
S. Ioffe ◽  
A. H. Jansen ◽  
V. Chernick
Keyword(s):  
Blood Pressure ◽  
Cerebral Cortex ◽  
Eye Movements ◽  
Duty Cycle ◽  
Chemical Control ◽  
Inspiratory Time ◽  
Obvious Effect ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Fetal Breathing

The effects of hypercapnia and hypoxemia on breathing movements were studied in 12 chronically decorticated fetal sheep, 127–140 days gestation. The fetal state of consciousness was defined in terms of activity of the lateral rectus and nuchal muscles. Arterial blood pressure was monitored. Fetal breathing was determined by integrated diaphragmatic electromyogram (EMG) and analyzed in terms of inspiratory time (TI), expiratory time (TE), electrical equivalent of tidal volume (EVT), breath interval (TT), duty cycle (TI/TT), mean inspiratory flow equivalent (EVT/TI), and instantaneous ventilation equivalent (EVT/TT). Fetal breathing occurred only during episodes of rapid-eye movements, and the response to hypercapnia consisted of an increase in EVT, TI, EVE, and EVT/TI and a decrease in the coefficient of variation of all measured parameters. Induction of hypoxia during episodes of spontaneous fetal breathing produced a decrease in the rate of breathing and an increase in EVT and TI with no change in the variability of all parameters studied. Since similar responses to hypercapnia and hypoxemia are seen in the intact fetus, we conclude that the cerebral cortex has no obvious effect on the chemical control of fetal breathing.

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.

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.

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