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Propofol administration to the maternal-fetal unit improved fetal EEG and influenced cerebral apoptotic pathway in preterm lambs suffering from severe asphyxia.

Seehase M, Jennekens W, Zwanenburg A, Andriessen P, Collins JJ, Kuypers E, Zimmermann LJ, Vles JSh, Gavilanes AW, Kramer BW - Mol Cell Pediatr (2015)

Bottom Line: UCO resulted in global asphyxia and cardiac arrest.Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. matthias.seehase@med.uni-goettingen.de.

ABSTRACT

Background: Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia.

Methods: Forty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers.

Results: Asphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.

Conclusions: Improvement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

No MeSH data available.


Related in: MedlinePlus

EEG during the postocclusion phase. A 15-min epoch of amplitude-integrated EEG during the postocclusion phase (top, x-axis shows time in minutes, y-axis shows the amplitude of the signal and is displayed semi-logarithmic: linear 0 to 10 μV and logarithmic 10 to 100 μV) shows a slight increase of the lower margin amplitude and increase of bandwidth, indicated by the shaded dark gray vertical band. Illustration of the accessory bilateral EEG during the shaded vertical band of the aEEG (bottom, time resolution 1 s/dotted vertical line, sensitivity indicated by vertical stick) showing repetitive sharp waves every 2 to 3 s, suggestive of seizure activity in the left hemisphere. The rectangular box indicates the period over which spectral analysis is performed and shows a relative delta power of 84%.
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Fig4: EEG during the postocclusion phase. A 15-min epoch of amplitude-integrated EEG during the postocclusion phase (top, x-axis shows time in minutes, y-axis shows the amplitude of the signal and is displayed semi-logarithmic: linear 0 to 10 μV and logarithmic 10 to 100 μV) shows a slight increase of the lower margin amplitude and increase of bandwidth, indicated by the shaded dark gray vertical band. Illustration of the accessory bilateral EEG during the shaded vertical band of the aEEG (bottom, time resolution 1 s/dotted vertical line, sensitivity indicated by vertical stick) showing repetitive sharp waves every 2 to 3 s, suggestive of seizure activity in the left hemisphere. The rectangular box indicates the period over which spectral analysis is performed and shows a relative delta power of 84%.

Mentions: During UCO, the aEEG pattern rapidly changed with upper margin amplitude values <10 μV, consistent with a low-voltage pattern (Figure 2). In isoflurane-treated lambs, we observed a 60% decrease in burst per minute during UCO, whereas in propofol-treated lambs a much smaller change of 20% was observed. In the post-UCO phase, we observed significantly more burst activity in the isoflurane lambs than in the propofol-treated lambs (median burst/minute 4.8 vs. 1.6, p < 0.05) (Figure 3A). Burst total spectral power during UCO increased more in isoflurane-treated lambs than in propofol-treated lambs (Figure 3B). Of the relative spectral power measures, δ1 and δ2 were particularly responsible for the increase of burst spectral power in isoflurane-treated lambs (Figure 3C). The increase of burst spectral power and relative delta activity was associated with characteristic repetitive patterns of sharp waves of the raw EEG, indicating seizure activity (Figure 4).Figure 4


Propofol administration to the maternal-fetal unit improved fetal EEG and influenced cerebral apoptotic pathway in preterm lambs suffering from severe asphyxia.

Seehase M, Jennekens W, Zwanenburg A, Andriessen P, Collins JJ, Kuypers E, Zimmermann LJ, Vles JSh, Gavilanes AW, Kramer BW - Mol Cell Pediatr (2015)

EEG during the postocclusion phase. A 15-min epoch of amplitude-integrated EEG during the postocclusion phase (top, x-axis shows time in minutes, y-axis shows the amplitude of the signal and is displayed semi-logarithmic: linear 0 to 10 μV and logarithmic 10 to 100 μV) shows a slight increase of the lower margin amplitude and increase of bandwidth, indicated by the shaded dark gray vertical band. Illustration of the accessory bilateral EEG during the shaded vertical band of the aEEG (bottom, time resolution 1 s/dotted vertical line, sensitivity indicated by vertical stick) showing repetitive sharp waves every 2 to 3 s, suggestive of seizure activity in the left hemisphere. The rectangular box indicates the period over which spectral analysis is performed and shows a relative delta power of 84%.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530565&req=5

Fig4: EEG during the postocclusion phase. A 15-min epoch of amplitude-integrated EEG during the postocclusion phase (top, x-axis shows time in minutes, y-axis shows the amplitude of the signal and is displayed semi-logarithmic: linear 0 to 10 μV and logarithmic 10 to 100 μV) shows a slight increase of the lower margin amplitude and increase of bandwidth, indicated by the shaded dark gray vertical band. Illustration of the accessory bilateral EEG during the shaded vertical band of the aEEG (bottom, time resolution 1 s/dotted vertical line, sensitivity indicated by vertical stick) showing repetitive sharp waves every 2 to 3 s, suggestive of seizure activity in the left hemisphere. The rectangular box indicates the period over which spectral analysis is performed and shows a relative delta power of 84%.
Mentions: During UCO, the aEEG pattern rapidly changed with upper margin amplitude values <10 μV, consistent with a low-voltage pattern (Figure 2). In isoflurane-treated lambs, we observed a 60% decrease in burst per minute during UCO, whereas in propofol-treated lambs a much smaller change of 20% was observed. In the post-UCO phase, we observed significantly more burst activity in the isoflurane lambs than in the propofol-treated lambs (median burst/minute 4.8 vs. 1.6, p < 0.05) (Figure 3A). Burst total spectral power during UCO increased more in isoflurane-treated lambs than in propofol-treated lambs (Figure 3B). Of the relative spectral power measures, δ1 and δ2 were particularly responsible for the increase of burst spectral power in isoflurane-treated lambs (Figure 3C). The increase of burst spectral power and relative delta activity was associated with characteristic repetitive patterns of sharp waves of the raw EEG, indicating seizure activity (Figure 4).Figure 4

Bottom Line: UCO resulted in global asphyxia and cardiac arrest.Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands. matthias.seehase@med.uni-goettingen.de.

ABSTRACT

Background: Term and near-term infants are at high risk of developing brain injury and life-long disability if they have suffered from severe perinatal asphyxia. We hypothesized that propofol administration to the maternal-fetal unit can diminish cerebral injury in term and near-term infant fetuses in states of progressive severe asphyxia.

Methods: Forty-four late preterm lambs underwent total umbilical cord occlusion (UCO) or sham treatment in utero. UCO resulted in global asphyxia and cardiac arrest. After emergency cesarean section under either maternal propofol or isoflurane anesthesia, the fetuses were resuscitated and subsequently anesthetized the same way as their mothers.

Results: Asphyctic lambs receiving isoflurane showed a significant increase of total and low-frequency spectral power in bursts indicating seizure activity and more burst-suppression with a marked increase of interburst interval length during UCO. Asphyctic lambs receiving propofol showed less EEG changes. Propofol increased levels of anti-apoptotic B-cell lymphoma-extra large (Bcl-xL) and phosphorylated STAT-3 and reduced the release of cytochrome c from the mitochondria and the protein levels of activated cysteinyl aspartate-specific protease (caspase)-3, -9, and N-methyl-d-aspartate (NMDA) receptor.

Conclusions: Improvement of fetal EEG during and after severe asphyxia could be achieved by propofol treatment of the ovine maternal-fetal unit. The underlying mechanism is probably the reduction of glutamate-induced cytotoxicity by down-regulation of NMDA receptors and an inhibition of the mitochondrial apoptotic pathway.

No MeSH data available.


Related in: MedlinePlus