scholarly journals Miniaturized Electrochemical Sensors to Monitor Fetal Hypoxia and Acidosis in a Pregnant Sheep Model

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1344
Author(s):  
Míriam Illa ◽  
Laura Pla ◽  
Sergio Berdún ◽  
Mònica Mir ◽  
Lourdes Rivas ◽  
...  
Keyword(s):  
Electrochemical Sensors ◽  
Perinatal Asphyxia ◽  
Surrogate Marker ◽  
Muscular Tissue ◽  
Fetal Hypoxia ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Histological Assessment ◽  
Ph Changes ◽  
Pregnant Sheep

Perinatal asphyxia is a major cause of severe brain damage and death. For its prenatal identification, Doppler ultrasound has been used as a surrogate marker of fetal hypoxia. However, Doppler evaluation cannot be performed continuously. We have evaluated the performance of a miniaturized multiparametric sensor aiming to evaluate tissular oxygen and pH changes continuously in an umbilical cord occlusion (UCO) sheep model. The electrochemical sensors were inserted in fetal hindlimb skeletal muscle and electrochemical signals were recorded. Fetal hemodynamic changes and metabolic status were also monitored during the experiment. Additionally, histological assessment of the tissue surrounding the sensors was performed. Both electrochemical sensors detected the pO2 and pH changes induced by the UCO and these changes were correlated with hemodynamic parameters as well as with pH and oxygen content in the blood. Finally, histological assessment revealed no signs of alteration on the same day of insertion. This study provides the first evidence showing the application of miniaturized multiparametric electrochemical sensors detecting changes in oxygen and pH in skeletal muscular tissue in a fetal sheep model.

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.

scholarly journals Airway inflammatory cell responses to intra-amniotic lipopolysaccharide in a sheep model of chorioamnionitis

2009 ◽  
Vol 296 (3) ◽  
pp. L384-L393 ◽  
Author(s):  
Fook-Choe Cheah ◽  
J. Jane Pillow ◽  
Boris W. Kramer ◽  
Graeme R. Polglase ◽  
Ilias Nitsos ◽  
...  
Keyword(s):  
Time Course ◽  
Fetal Lung ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Protein Carbonyls ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Nitrative Stress ◽  
Maturation Factor ◽  
Oxidative Burst Activity

Chorioamnionitis, a risk factor for bronchopulmonary dysplasia in preterm infants, causes an influx of inflammatory cells into the fetal lung. Using a fetal sheep model, we evaluated the time course of activation, functional maturity, and apoptosis of the leukocytes recruited to the fetal air spaces by lipopolysaccharide (LPS). Time-mated sheep were given intra-amniotic injections with 10 mg of Escherichia coli LPS or saline 2 or 7 days before preterm delivery at 124 days of gestation (term is 150 days). Both neutrophils and monocytes in bronchoalveolar lavage fluid (BALF) had activated NF-κB after 2- and 7-day LPS exposures. These neutrophils and monocytes expressed the activation factor CD11b and the maturation factor PU.1 at 2 days, and increased PU.1 expression was detected in macrophages at 7 days. Leukocyte oxidative burst activity was greatest at 7 days. BALF lipid peroxidation increased fivefold at 2 days, while protein carbonyls increased eightfold at 7 days. Nitrative stress was not detected in the BALF, but leukocytes in the lung expressed nitric oxide synthase (NOS)II (inducible NOS). BALF leukocytes expressed the antioxidant peroxiredoxin V. Lung glutathione peroxidase was also increased with LPS exposure. There was minimal apoptosis of airway and lung leukocytes assessed by caspase-3 activation. Intra-amniotic LPS recruits leukocytes to the fetal air space that have a persistent activation. These results have implications for the pathogenesis of lung inflammatory disorders in the preterm.

scholarly journals Does heart rate variability reflect the systemic inflammatory response in a fetal sheep model of lipopolysaccharide-induced sepsis?

2015 ◽  
Vol 36 (10) ◽  
pp. 2089-2102 ◽  
Author(s):  
Lucien D Durosier ◽  
Christophe L Herry ◽  
Marina Cortes ◽  
Mingju Cao ◽  
Patrick Burns ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Inflammatory Response ◽  
Systemic Inflammatory Response ◽  
Sheep Model ◽  
Fetal Sheep

Left-right difference in fetal liver oxygenation during hypoxia estimated by BOLD MRI in a fetal sheep model

2011 ◽  
Vol 38 (6) ◽  
pp. 665-672 ◽  
Author(s):  
A. Sørensen ◽  
D. Holm ◽  
M. Pedersen ◽  
A. Tietze ◽  
B. Stausbøl-Grøn ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Bold Mri

scholarly journals A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0180653 ◽  
Author(s):  
C. Garabedian ◽  
C. Champion ◽  
E. Servan-Schreiber ◽  
L. Butruille ◽  
E. Aubry ◽  
...  
Keyword(s):  
Heart Rate ◽  
Experimental Study ◽  
Heart Rate Variability ◽  
Parasympathetic Activity ◽  
Sheep Model ◽  
Fetal Sheep

scholarly journals Serotonin contributes to high pulmonary vascular tone in a sheep model of persistent pulmonary hypertension of the newborn

2013 ◽  
Vol 304 (12) ◽  
pp. L894-L901 ◽  
Author(s):  
Cassidy Delaney ◽  
Jason Gien ◽  
Gates Roe ◽  
Nicole Isenberg ◽  
Jenai Kailey ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Tryptophan Hydroxylase ◽  
Late Gestation ◽  
Persistent Pulmonary Hypertension ◽  
Sheep Model ◽  
Pulmonary Hemodynamics ◽  
Fetal Sheep ◽  
Pulmonary Arterial

Although past studies demonstrate that altered serotonin (5-HT) signaling is present in adults with idiopathic pulmonary arterial hypertension, whether serotonin contributes to the pathogenesis of persistent pulmonary hypertension of the newborn (PPHN) is unknown. We hypothesized that 5-HT contributes to increased pulmonary vascular resistance (PVR) in a sheep model of PPHN and that selective 5-HT reuptake inhibitor (SSRI) treatment increases PVR in this model. We studied the hemodynamic effects of 5-HT, ketanserin (5-HT2A receptor antagonist), and sertraline, an SSRI, on pulmonary hemodynamics of the late gestation fetal sheep with PPHN caused by prolonged constriction of the ductus arteriosis. Brief intrapulmonary infusions of 5-HT increased PVR from 1.0 ± 0.07 (baseline) to 1.4 ± 0.22 mmHg/ml per minute of treatment ( P < 0.05). Ketanserin decreased PVR from 1.1 ± 0.15 (baseline) to 0.82 ± 0.09 mmHg/ml per minute of treatment ( P < 0.05). Sertraline increased PVR from 1.1 ± 0.17 (baseline) to 1.4 ± 0.17 mmHg/ml per minute of treatment ( P = 0.01). In addition, we studied 5-HT production and activity in vitro in experimental PPHN. Compared with controls, pulmonary artery endothelial cells from fetal sheep with PPHN exhibited increased expression of tryptophan hydroxylase 1 and 5-HT production by twofold and 56%, respectively. Compared with controls, 5-HT2A R expression was increased in lung homogenates and pulmonary artery smooth muscle cell lysates by 35% and 32%, respectively. We concluded that increased 5-HT contributes to high PVR in experimental PPHN through activation of the 5-HT2A receptor and that SSRI infusion further increases PVR in this model.

scholarly journals Fetoscopic abdominal decompression of congenital diaphragmatic hernia – preliminary results of a fetal sheep model

2014 ◽  
Author(s):  
Felipe Fromm ◽  
Katharina Wenke ◽  
Thomas Krebs ◽  
Michael Boettcher ◽  
Georg Eschenburg ◽  
...  
Keyword(s):  
Animal Model ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Fetal Surgery ◽  
Amniotic Cavity ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Tracheal Occlusion ◽  
Animal Trials ◽  
Abdominal Decompression

Background Severe congenital diaphragmatic hernia (CDH) is prenatally managed by fetoscopic tracheal occlusion (FETO) to improve lung growth and maturation. As FETO is not able to reduce the pressure onto the developing lungs originating from the intestine growing into the thoracic cavity, fetal abdominal decompression may alleviate this pressure effect by directing the growing intestine into the amniotic cavity away from the lungs. Therefore, aim of this study was to establish an animal model for fetoscopic abdominal decompression in fetal sheep with CDH. Methods CDH was created surgically on day 75 of 145 day gestation in eight fetuses. 2-3 weeks later, an opening was created in the fetal abdomen by fetoscopic surgery. The fetuses were retrieved by cesarean section at the end of pregnancy and evaluated. Results Five fetuses with CDH were treated with fetoscopic abdominal decompression. Three fetuses with CDH were taken as controls. One fetus was lost after creation of the CDH and two other after creation of the abdominal defect. Preliminary sterological results showed that the septal thickness of the experimental group was smaller than in the CDH group. Conclusion This study demonstrates the general feasibility of fetoscopic abdominal decompression for diaphragmatic hernia in our new animal model. Although not statistically significant, the lungs of treated fetuses were larger and heavier than those of untreated controls. Our findings support the hypothesis of palliative fetal surgery for severe CDH compared to tracheal occlusion. More controlled animal trials are needed.

Peripheral chemoreflex activation and cardiac function during hypoxemia in near term fetal sheep without placental compromise

2021 ◽  
Author(s):  
Juulia Lantto ◽  
Tiina Erkinaro ◽  
Mervi Haapsamo ◽  
Heikki Huhta ◽  
Leena Alanne ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Carotid Artery ◽  
Arterial Oxygen ◽  
Sheep Model ◽  
Fetal Sheep ◽  
Descending Aorta ◽  
Arterial Blood ◽  
Near Term ◽  
Peripheral Chemoreflex

A drop in arterial oxygen content activates fetal chemoreflex including an increase in sympathetic activity leading to peripheral vasoconstriction and redistribution of blood flow to protect the brain, myocardium, and adrenal glands. By using a chronically instrumented fetal sheep model with intact placental circulation at near-term gestation, we investigated the relationship between peripheral chemoreflex activation induced by hypoxemia and central hemodynamics. 17 Åland landrace sheep fetuses at 115-128/145 gestational days were instrumented. Carotid artery was catheterised in 10 fetuses and descending aorta in 7 fetuses. After a 4-day recovery, baseline measurements of fetal arterial blood pressures, blood gas values, and fetal cardiovascular hemodynamics by pulsed Doppler ultrasonography were obtained under isoflurane-anesthesia. Comparable data to baseline was collected 10 (acute hypoxemia) and 60 minutes (prolonged hypoxemia) after maternal hypo-oxygenation to saturation level of 70-80% was achieved. During prolonged hypoxemia, pH and base excess (BE) were lower, and lactate levels higher in the descending aorta than in the carotid artery. During hypoxemia mean arterial blood pressure (MAP) in the descending aorta increased, while in the carotid artery MAP decreased. In addition, right pulmonary artery pulsatility index values increased, and the diastolic component in the aortic isthmus blood flow velocity waveform became more retrograde. Both fetal ventricular cardiac outputs were maintained even during prolonged hypoxemia when significant fetal metabolic acidemia developed. Fetal chemoreflex activation induced by hypoxemia decreased the perfusion pressure in the cerebral circulation. Fetal weight-indexed LVCO or AoI Net Flow-ratio did not correlate with a drop in carotid artery blood pressure.

Homing of Human Cells in the Fetal Sheep Model: Modulation by Antibodies Activating or Inhibiting Very Late Activation Antigen-4–Dependent Function

Blood ◽  
1999 ◽  
Vol 94 (7) ◽  
pp. 2515-2522 ◽  
Author(s):  
Esmail D. Zanjani ◽  
Alan W. Flake ◽  
Graça Almeida-Porada ◽  
Nam Tran ◽  
Thalia Papayannopoulou
Keyword(s):  
Molecular Mechanisms ◽  
Fetal Liver ◽  
In Utero ◽  
Human Cells ◽  
Human Donor ◽  
Sheep Model ◽  
Fetal Sheep ◽  
In Utero Transplantation ◽  
Donor Cells ◽  
Activation Antigen

The mechanisms by which intravenously (IV)-administered hematopoietic cells home to the bone marrow (BM) are poorly defined. Although insightful information has been obtained in mice, our knowledge about homing of human cells is very limited. In the present study, we investigated the importance of very late activation antigen (VLA)-4 in the early phases of lodgment of human CD34+progenitors into the sheep hematopoietic compartment after in utero transplantation. We have found that preincubation of donor cells with anti–VLA-4 blocking antibodies resulted in a profound reduction of human cell lodgment in the fetal BM at 24 and 48 hours after transplantation, with a corresponding increase of human cells in the peripheral circulation. Furthermore, IV infusion of the anti–VLA-4 antibody at later times (posttransplantation days 21 to 24) resulted in redistribution or mobilization of human progenitors from the BM to the peripheral blood. In an attempt to positively modulate homing, we also pretreated human donor cells with an activating antibody to β1 integrins. This treatment resulted in increased lodgment of donor cells in the fetal liver, presumably for hemodynamic reasons, at the expense of the BM. Given previous involvement of the VLA-4/vascular cell adhesion molecule (VCAM)-1 adhesion pathway in homing and mobilization in the murine system, our present data suggest that cross-reacting ligands (likely VCAM-1) for human VLA-4 exist in sheep BM, thereby implicating conservation of molecular mechanisms of homing and mobilization across disparate species barriers. Thus, information from xenogeneic models of human hematopoiesis and specifically, the human/sheep model of in utero transplantation, may provide valuable insights into human hematopoietic transplantation biology.

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