Adenosine stimulates breathing in fetal sheep with brain stem section

1992 ◽  
Vol 72 (1) ◽  
pp. 94-99 ◽  
Author(s):  
B. J. Koos ◽  
A. Chao ◽  
W. Doany
Keyword(s):  
Brain Stem ◽  
Blood Gases ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Arterial Infusion ◽  
Fetal Sheep ◽  
Stem Section ◽  
Peripheral Arterial ◽  
Arterial Po2 ◽  
The Brain ◽  
Pontomedullary Junction

Breathing responses to adenosine were determined in 12 chronically catheterized fetal sheep (greater than 0.8 term) in which hypoxic inhibition of breathing had been eliminated by brain stem section. The caudal extent of transection varied from the rostral midbrain to the pontomedullary junction. Isocapnic hypoxia [delta arterial PO2 (PaO2) of -12 Torr] doubled the incidence and depth of breathing activity and increased the incidence of eye movements. Intra-arterial infusion of adenosine (0.30 +/- 0.03 mg.min-1.kg fetal wt-1) increased the incidence and amplitude of breathing without affecting blood gases. Adenosine did not significantly alter the incidence of eye activity. Intra-arterial injection of oligomycin (120 +/- 26 micrograms/kg fetal wt), an inhibitor of mitochondrial oxidative phosphorylation, also stimulated breathing activity. In four fetuses with brain stem section, peripheral arterial chemodenervation blunted the stimulatory effects of hypoxia on breathing activity and abolished altogether the excitatory effects of adenosine. It is concluded that 1) hypoxia and adenosine likely inhibit breathing in normal fetuses by affecting similar areas of the brain stem and 2) in fetuses with brain section, hypoxic hyperpnea depends on peripheral and central mechanisms, whereas adenosine stimulates breathing via the peripheral arterial chemoreceptors.

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.

Genesis of rhythmic respiratory activity in pons independent of medulla

1985 ◽  
Vol 59 (3) ◽  
pp. 684-690 ◽  
Author(s):  
W. M. St John ◽  
T. A. Bledsoe
Keyword(s):  
Brain Stem ◽  
Phrenic Nerve ◽  
Respiratory Activity ◽  
Respiratory Rhythm ◽  
Related Activity ◽  
Pharmacological Agents ◽  
Pneumotaxic Center ◽  
Trigeminal Nerves ◽  
The Brain ◽  
Pontomedullary Junction

We hypothesized that rhythmic respiratory-related activity could be generated in pons independent of medullary mechanisms. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, we recorded efferent activities of the phrenic nerve and mylohyoid branch of the trigeminal nerve. Following transections of the brain stem at the pontomedullary junction, the phrenic and trigeminal nerves discharged with independent rhythms. Spontaneous trigeminal discharges eventually ceased but were reestablished after strychnine, doxapram, and/or protriptyline were administered. In some animals having no spontaneous trigeminal discharges after transection, these discharges appeared, with a rhythm different from the phrenic, following administration of these agents. In other cats having no transections between pons and medulla, these pharmacological agents induced trigeminal and phrenic discharges after kainic acid had been injected into the entire dorsal and ventral medullary respiratory nuclei. Phrenic and trigeminal discharges were linked, indicating survival of bulbospinal neurons or presence of pontospinal units. We conclude that rhythms, similar to respiratory rhythm, can occur by mechanisms in isolated pons. Such mechanisms are hypothesized to be within the pneumotaxic center and may underlie the neurogenesis of eupnea.

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.

Independent brain stem sites for ventilatory neurogenesis

1983 ◽  
Vol 55 (2) ◽  
pp. 433-439 ◽  
Author(s):  
W. M. St John
Keyword(s):  
Brain Stem ◽  
Pacemaker Cells ◽  
Stem Section ◽  
Pontomedullary Junction

The purpose was to determine if independent ventilatory rhythms could be generated in each half of completely separated brain stems. In decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats, activities of phrenic, recurrent laryngeal (RLN), and/or hypoglossal nerves were monitored. Midsaggital brain stem divisions were performed by sections and lesions. Eupnea continued following divisions of mesencephalon and pons. Hypoglossal and phrenic activities were eliminated after sections approximating the obex. In most preparations, RLNs discharged with independent rhythms after completion of midsagittal brain stem section and a C1 transection. Independent rhythms were also obtained from each half of medulla following transections at the pontomedullary junction and at C1, and midsagittal medullary divisions. In other animals with transections between pons and medulla and at C1, synchronized RLN and hypoglossal activities persisted after sagittal medullary divisions, 2.0 mm lateral to midline contralaterally. Data demonstrate that there is more than one potential brain stem site for ventilatory neurogenesis. It is hypothesized that there are many such sites, possibly having pacemaker cells, in pons and medulla.

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.

Brain stem augmentation of cardiovascular activity

1960 ◽  
Vol 198 (2) ◽  
pp. 421-423 ◽  
Author(s):  
Richard L. Glasser
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Brain Stem ◽  
Cardiovascular Activity ◽  
Rostral Portion ◽  
The Brain ◽  
Pontomedullary Junction

Midpontile ischemic decerebration in vagotomized mesencephalic cats produced marked tachycardia and hypertension. Subsequent transection of the brain stem at or above the midpontile level did not affect the cardiovascular hyperactivity. Transection at the pontomedullary junction abolished the brain stem augmentation of heart rate and blood pressure. The results suggest the existence of a cardiovascular augmenter area in the caudal half of the pons and a cardiovascular depressor area in a more rostral portion of the brain stem.

Dynamics of the ventilatory response to central hypoxia in cats

1990 ◽  
Vol 68 (3) ◽  
pp. 1107-1113 ◽  
Author(s):  
D. S. Ward ◽  
A. Berkenbosch ◽  
J. DeGoede ◽  
C. N. Olievier
Keyword(s):  
Brain Stem ◽  
Ventilatory Response ◽  
Roller Pump ◽  
Arterial Pco2 ◽  
Time Constants ◽  
Long Latency ◽  
Alpha Chloralose ◽  
Arterial Po2 ◽  
The Brain ◽  
Single Exponential Function

The dynamics of the effect of central hypoxia on ventilation were investigated by the technique of artificial perfusion of the brain stem in alpha-chloralose-urethan-anesthetized cats. A two-channel roller pump and a four-way valve allowed switching the gas exchanger into and out of the extracorporeal circuit which controlled the brain stem perfusion. When isocapnic hypoxia (arterial PO2 range 18-59 Torr) was limited to the brain stem, a decline in ventilation was consistently found. In 12 cats 47 steps into and 48 steps out of central hypoxia were made. The ventilatory response was fitted using least squares with a model that consisted of a latency followed by a single-exponential function. The latencies for the steps into and out of hypoxia were not significantly different (P = 0.14) and were 32.3 +/- 4.0 and 25.1 +/- 3.6 (SE) s, respectively. The time constant for the steps into hypoxia (149.7 +/- 8.5 s) was significantly longer (P = 0.0002) than for the steps out of hypoxia (105.5 +/- 10.1 s). The time constants for the increase and decrease in ventilation after step changes in the central arterial PCO2 found in a previous study (J. Appl. Physiol. 66: 2168-2172, 1989) were not significantly different (P greater than 0.2) from the corresponding time constants in this study (for 7 cats common to both studies). Theories of the mechanisms behind hypoxic ventilatory decline need to account for the long latency, the similarity between the time constants for the ventilatory response to O2 and CO2, and the differences between the time constants for increasing and decreasing ventilation.

Effect of Ethanol on 15-Hydroxyprostaglandin Dehydrogenase Activity in the Brain Stem of the Near-Term Fetal Sheep

1991 ◽  
Vol 16 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Deirdre Treissman ◽  
Graeme N. Smith ◽  
John Patrick ◽  
James F. Brien
Keyword(s):  
Brain Stem ◽  
Dehydrogenase Activity ◽  
Fetal Sheep ◽  
Near Term ◽  
The Brain

Respiratory Effects of H+ and Dinitrophenol Injections into the Brain Stem Subarachnoid Space of Fetal Lambs

1975 ◽  
Vol 53 (5) ◽  
pp. 726-733 ◽  
Author(s):  
A. H. Jansen ◽  
B. J. Russell ◽  
V. Chernick
Keyword(s):  
Brain Stem ◽  
Subarachnoid Space ◽  
Extracellular Fluid ◽  
Ventral Surface ◽  
Metabolic Inhibitors ◽  
Blood Gas ◽  
Respiratory Response ◽  
Fetal Sheep ◽  
Arterial Ph ◽  
The Brain

Mock cerebrospinal fluid (pH 5.37–8.38) or 2,4-dinitrophenol (DNP) (0.15–1.5 mg) was injected into the subarachnoid space of the ventral brain stem of exteriorized fetal sheep. Changes in pH on the ventral surface of the medulla did not stimulate respiratory efforts or induce significant cardiovascular changes. The respiratory response to DNP injections ranged from no response to prolonged rhythmic ventilation that was independent of the peripheral chemoreceptors or the control arterial pH and blood gas tensions. This inconsistency suggests an effector site somewhat removed from the immediate surface of the medulla. The heart rate and blood pressure were not affected. It is concluded that increased H+ concentration in the extracellular fluid of the fetal ventral medulla does not initiate respiration, and any respiratory response to metabolic inhibitors applied to this area therefore is not attributable to a secondary change in surface pH.

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