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Maturation of the mitochondrial redox response to profound asphyxia in fetal sheep.

Drury PP, Bennet L, Booth LC, Davidson JO, Wassink G, Gunn AJ - PLoS ONE (2012)

Bottom Line: Occlusion was associated with profound, rapid fall in ΔHb in all groups to a plateau from 6 min, greatest at 0.85 ga compared to 0.6 and 0.7 ga (p<0.05).Cerebral impedance (a measure of cytotoxic edema) increased earlier and more rapidly with greater gestation.In conclusion, the more rapid rise in CytOx and cortical impedance during profound asphyxia with greater maturation is consistent with increasing dependence on oxidative metabolism leading to earlier onset of neural energy failure before the onset of systemic hypotension.

View Article: PubMed Central - PubMed

Affiliation: Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.

ABSTRACT

Unlabelled: Fetal susceptibility to hypoxic brain injury increases over the last third of gestation. This study examined the hypothesis that this is associated with impaired mitochondrial adaptation, as measured by more rapid oxidation of cytochrome oxidase (CytOx) during profound asphyxia.

Methods: Chronically instrumented fetal sheep at 0.6, 0.7, and 0.85 gestation were subjected to either 30 min (0.6 gestational age (ga), n = 6), 25 min (0.7 ga, n = 27) or 15 min (0.85 ga, n = 17) of complete umbilical cord occlusion. Fetal EEG, cerebral impedance (to measure brain swelling) and near-infrared spectroscopy-derived intra-cerebral oxygenation (ΔHb = HbO(2) - Hb), total hemoglobin (THb) and CytOx redox state were monitored continuously. Occlusion was associated with profound, rapid fall in ΔHb in all groups to a plateau from 6 min, greatest at 0.85 ga compared to 0.6 and 0.7 ga (p<0.05). THb initially increased at all ages, with the greatest rise at 0.85 ga (p<0.05), followed by a progressive fall from 7 min in all groups. CytOx initially increased in all groups with the greatest rise at 0.85 ga (p<0.05), followed by a further, delayed increase in preterm fetuses, but a striking fall in the 0.85 group after 6 min of occlusion. Cerebral impedance (a measure of cytotoxic edema) increased earlier and more rapidly with greater gestation. In conclusion, the more rapid rise in CytOx and cortical impedance during profound asphyxia with greater maturation is consistent with increasing dependence on oxidative metabolism leading to earlier onset of neural energy failure before the onset of systemic hypotension.

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Changes in EEG power, spectral edge frequency, and cortical impedance during occlusion.Data are minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; *: p<0.05 for 0.6 vs. 0.7 groups.
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pone-0039273-g002: Changes in EEG power, spectral edge frequency, and cortical impedance during occlusion.Data are minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; *: p<0.05 for 0.6 vs. 0.7 groups.

Mentions: EEG power was significantly higher at baseline in the 0.85 group compared to the 0.7 and 0.6 ga groups (20.4±0.5 vs. 15.9±0.5 and 14.5±0.9 dB respectively, p<0.05, Figure 2). Occlusion was associated with rapid suppression of EEG activity in all groups, with the greatest fall in the 0.85 ga group (EEG power at 2 min of occlusion: 2.1±0.8 dB vs 5.4±1.0 dB in the 0.7 ga and 5.6±1.5 dB in the 0.6 ga groups, p<0.05). There were no significant differences between the 0.6 and 0.7 ga groups. Spectral edge was significantly lower at baseline in the 0.6 ga compared to the 0.7 ga and 0.85 ga groups (7.1±0.7 Hz vs. 10.1±0.4 Hz and 10.4±0.4 Hz respectively, p<0.05). All groups showed a rapid suppression of spectral edge frequency with no difference between groups during occlusion. Cortical impedance showed a progressive increase in all groups from several min after the start of occlusion. The relative rise in cortical impedance increased with increasing gestational age; the 0.7 group was significantly greater than the 0.6 group from 9 min (p<0.05) and the 0.85 group was significantly higher than the 0.6 and 0.7 group from 2–15 min (p<0.05). At 10 min of occlusion there was a clear maturation dependent difference in impedance (103±1%, 106±1%, and 129±3%, for 0.6, 0.7, and 0.85 ga respectively, p<0.05). The final maxima, at the end of occlusion, were similar between groups (132±4%, 135±4%, and 138±5%).


Maturation of the mitochondrial redox response to profound asphyxia in fetal sheep.

Drury PP, Bennet L, Booth LC, Davidson JO, Wassink G, Gunn AJ - PLoS ONE (2012)

Changes in EEG power, spectral edge frequency, and cortical impedance during occlusion.Data are minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; *: p<0.05 for 0.6 vs. 0.7 groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376132&req=5

pone-0039273-g002: Changes in EEG power, spectral edge frequency, and cortical impedance during occlusion.Data are minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; *: p<0.05 for 0.6 vs. 0.7 groups.
Mentions: EEG power was significantly higher at baseline in the 0.85 group compared to the 0.7 and 0.6 ga groups (20.4±0.5 vs. 15.9±0.5 and 14.5±0.9 dB respectively, p<0.05, Figure 2). Occlusion was associated with rapid suppression of EEG activity in all groups, with the greatest fall in the 0.85 ga group (EEG power at 2 min of occlusion: 2.1±0.8 dB vs 5.4±1.0 dB in the 0.7 ga and 5.6±1.5 dB in the 0.6 ga groups, p<0.05). There were no significant differences between the 0.6 and 0.7 ga groups. Spectral edge was significantly lower at baseline in the 0.6 ga compared to the 0.7 ga and 0.85 ga groups (7.1±0.7 Hz vs. 10.1±0.4 Hz and 10.4±0.4 Hz respectively, p<0.05). All groups showed a rapid suppression of spectral edge frequency with no difference between groups during occlusion. Cortical impedance showed a progressive increase in all groups from several min after the start of occlusion. The relative rise in cortical impedance increased with increasing gestational age; the 0.7 group was significantly greater than the 0.6 group from 9 min (p<0.05) and the 0.85 group was significantly higher than the 0.6 and 0.7 group from 2–15 min (p<0.05). At 10 min of occlusion there was a clear maturation dependent difference in impedance (103±1%, 106±1%, and 129±3%, for 0.6, 0.7, and 0.85 ga respectively, p<0.05). The final maxima, at the end of occlusion, were similar between groups (132±4%, 135±4%, and 138±5%).

Bottom Line: Occlusion was associated with profound, rapid fall in ΔHb in all groups to a plateau from 6 min, greatest at 0.85 ga compared to 0.6 and 0.7 ga (p<0.05).Cerebral impedance (a measure of cytotoxic edema) increased earlier and more rapidly with greater gestation.In conclusion, the more rapid rise in CytOx and cortical impedance during profound asphyxia with greater maturation is consistent with increasing dependence on oxidative metabolism leading to earlier onset of neural energy failure before the onset of systemic hypotension.

View Article: PubMed Central - PubMed

Affiliation: Fetal Physiology and Neuroscience Group, Department of Physiology, The University of Auckland, Auckland, New Zealand.

ABSTRACT

Unlabelled: Fetal susceptibility to hypoxic brain injury increases over the last third of gestation. This study examined the hypothesis that this is associated with impaired mitochondrial adaptation, as measured by more rapid oxidation of cytochrome oxidase (CytOx) during profound asphyxia.

Methods: Chronically instrumented fetal sheep at 0.6, 0.7, and 0.85 gestation were subjected to either 30 min (0.6 gestational age (ga), n = 6), 25 min (0.7 ga, n = 27) or 15 min (0.85 ga, n = 17) of complete umbilical cord occlusion. Fetal EEG, cerebral impedance (to measure brain swelling) and near-infrared spectroscopy-derived intra-cerebral oxygenation (ΔHb = HbO(2) - Hb), total hemoglobin (THb) and CytOx redox state were monitored continuously. Occlusion was associated with profound, rapid fall in ΔHb in all groups to a plateau from 6 min, greatest at 0.85 ga compared to 0.6 and 0.7 ga (p<0.05). THb initially increased at all ages, with the greatest rise at 0.85 ga (p<0.05), followed by a progressive fall from 7 min in all groups. CytOx initially increased in all groups with the greatest rise at 0.85 ga (p<0.05), followed by a further, delayed increase in preterm fetuses, but a striking fall in the 0.85 group after 6 min of occlusion. Cerebral impedance (a measure of cytotoxic edema) increased earlier and more rapidly with greater gestation. In conclusion, the more rapid rise in CytOx and cortical impedance during profound asphyxia with greater maturation is consistent with increasing dependence on oxidative metabolism leading to earlier onset of neural energy failure before the onset of systemic hypotension.

Show MeSH
Related in: MedlinePlus