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.

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.

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.

Fetal breathing and sleep state responses to graded carboxyhemoglobinemia in sheep

1988 ◽  
Vol 65 (5) ◽  
pp. 2118-2123 ◽  
Author(s):  
B. J. Koos ◽  
K. Matsuda ◽  
G. G. Power
Keyword(s):  
Dependent Manner ◽  
Sleep State ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Arterial Ph ◽  
Tissue Po2 ◽  
Fetal Breathing ◽  
Peripheral Arterial ◽  
State Responses ◽  
Dose Dependent

To investigate CO effects on brain oxygenation, graded carboxyhemoglobinemia (HbCO) was produced in nine unanesthetized fetal sheep by infusing CO-laden erythrocytes in exchange for fetal blood. For the 1st h after this procedure, the mean fetal carboxyhemoglobin levels were 16.5 +/- 0.4% [control (C) = 1.4 +/- 0.4%] for mild HbCO, 22.7 +/- 0.6% (C = 1.8 +/- 0.4%) for moderate HbCO, and 27.8 +/- 0.5% (C = 2.1 +/- 0.7%) for severe HbCO. This induction of HbCO significantly reduced mean preductal arterial PO2 values to 4.3 Torr below control for mild HbCO, 4.6 Torr below control for moderate HbCO, and 5.5 Torr below control for severe HbCO. The respective arterial O2 contents were decreased by 17, 21, and 29%. Mean arterial pH was lowered only during severe HbCO, and arterial PCO2 values were unchanged. HbCO produced a fetal tachycardia. Mean arterial blood pressure was only increased during severe HbCO. The incidences of rapid eye movements and breathing activity were decreased by HbCO in a dose-dependent manner. When related to calculated brain tissue PO2, these decreases were similar to those measured during hypoxic hypoxia and anemia, suggesting that carboxyhemoglobin effects result solely from diminished oxygenation. It is concluded that 1) the peripheral arterial chemoreceptors in the fetus apparently have little effect on hypoxic inhibition of breathing and 2) the carboxyhemoglobin concentrations required to inhibit fetal breathing are greater than those likely to be encountered clinically.

Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brain stems in vitro

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell
Keyword(s):  
Brain Stem ◽  
Respiratory Activity ◽  
Dependent Manner ◽  
Frequency Increase ◽  
Burst Frequency ◽  
Bath Application ◽  
Burst Amplitude ◽  
Dose Dependent ◽  
The Brain

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.

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.

Antithrombin-heparin covalent complex reduces microemboli during cardiopulmonary bypass in a pig model

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5716-5723 ◽  
Author(s):  
Petr Klement ◽  
Leslie R. Berry ◽  
Peng Liao ◽  
Henry Wood ◽  
Paul Tressel ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Dependent Manner ◽  
Direct Proportion ◽  
Flow Probe ◽  
Transient Signals ◽  
Neurocognitive Dysfunction ◽  
Yorkshire Pigs ◽  
Dose Dependent ◽  
The Brain ◽  
Covalent Complex

AbstractTranscranial Doppler-detected high-intensity transient signals (HITS) during cardiopulmonary bypass (CPB) surgery have been associated with postoperative neurocognitive dysfunction, suggesting microemboli in the brain could be a contributing factor. HITS occur despite administration of unfractionated heparin (UFH). This study was done to determine whether antithrombin-heparin covalent complex (ATH), a more potent anticoagulant than heparin, can reduce HITS during CPB. In a pig CPB model, ATH, UFH, or UFH + antithrombin (AT) was intravenously administered to female Yorkshire pigs after sternotomy. Twenty minutes later, hypothermic CPB was initiated and continued for 1.25 hours, then normothermia was re-established for 45 minutes. Protamine sulfate was given to neutralize the anticoagulants, and pigs were allowed to recover. HITS were monitored using an arterial flow probe placed over the carotid artery. Compared with UFH (300 or 1000 U/kg), ATH reduced the number of HITS during CPB in a dose-dependent manner. AT (3 mg/kg) + UFH (300 U/kg) resulted in an intermediate HITS rate between UFH and ATH (2 mg/kg in terms of AT). Examination of brain sections for emboli formation confirmed that, similar to HITS, number of thrombi decreased in direct proportion to ATH dosage. These results support the hypotheses that the majority of HITS represent thromboemboli and that ATH reduces emboli formation during CPB.

scholarly journals The Antiviral Effect of Novel Steroidal Derivatives on Flaviviruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Luping Zhang ◽  
Dengyuan Zhou ◽  
Qiuyan Li ◽  
Shuo Zhu ◽  
Muhammad Imran ◽  
...  
Keyword(s):  
Antiviral Effect ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
Design And Synthesis ◽  
Invasion Stage ◽  
Synthetic Derivatives ◽  
Dose Dependent ◽  
The Brain

Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both in vitro and in vivo. Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.

scholarly journals ANTI-PARKINSON ACTIVITY OF AQUEOUS EXTRACT OF LEAVES OF MURRAYA KOENIGII AGAINST PARAQUAT-INDUCED PARKINSONISM IN WISTAR RATS

2020 ◽  
pp. 150-153
Author(s):  
MAHESWARI REDDY B ◽  
DHANAPAL CK ◽  
LAKSHMI BVS
Keyword(s):  
Motor Performance ◽  
Chronic Administration ◽  
Motor Dysfunction ◽  
Muscle Rigidity ◽  
Dependent Manner ◽  
Murraya Koenigii ◽  
Behavioral Parameters ◽  
Dose Dependent ◽  
The Brain

Objective: The current study evaluates anti-Parkinson’s activity of aqueous extracts of leaves of Murraya koenigii (MK) (AEMK) against paraquat (PQ)-induced Parkinsonism in rats. Methods: In this study, effects of MK (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters such as catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters malondialdehyde, catalase (CAT), glutathione (GSH) reductase, GSH peroxidase, and GSH in rats. Results: Parkinson’s disease was induced by administering PQ 10 mg/kg b.w/i.p once in a week for 4 weeks. The increased cataleptic scores were significantly (p<0.001) found to be reduced, with the AEMK in a dose-dependent manner. Chronic administration of PQ significantly induced motor dysfunction (muscle rigidity and hypolocomotion), showed a significant increase in lipid peroxidation level, and depleted the levels of GSH, CAT, and reduced GSH. Daily administration of AEMK significantly improved motor performance and also significantly attenuated oxidative damage. Conclusion: The study proved that MK treatment significantly attenuated motor defects and also protected the brain from oxidative stress.

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.

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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