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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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Related in: MedlinePlus

Changes in mean arterial pressure (MAP), fetal heart rate (FHR), carotid artery blood flow (CaBF) and cortical laser Doppler flow (LDF) 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-g001: Changes in mean arterial pressure (MAP), fetal heart rate (FHR), carotid artery blood flow (CaBF) and cortical laser Doppler flow (LDF) 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: Occlusion was associated with an initial increase in MAP, followed by a rapid fall below baseline values and ultimately with profound hypotension at all ages. MAP was significantly higher in the 0.85 group at baseline (43.3±1.3 vs. 35.6±0.6 and 36.4±0.6 mmHg in the 0.6 and 0.7 ga groups respectively, p<0.05) and for the first 6 minutes of occlusion compared to 0.6 and 0.7 ga fetuses (p<0.05). MAP was also significantly higher over the first 2–7 min in the 0.7 ga compared to the 0.6 ga group (p<0.05). The onset of hypotension occurred earlier with increasing gestation (Figure 1). MAP fell significantly below baseline at 8 min the 0.85 ga group, and 9 min in the 0.6 and 0.7 ga groups. FHR was significantly lower at baseline in the 0.85 ga group compared to the 0.6 and 0.7 ga groups (178±5 bpm vs. 191±3 bpm in both 0.6 and 0.7 ga groups, p<0.05). Occlusion was associated with rapid bradycardia followed by a similar gradual further fall in all groups.


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 mean arterial pressure (MAP), fetal heart rate (FHR), carotid artery blood flow (CaBF) and cortical laser Doppler flow (LDF) 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-g001: Changes in mean arterial pressure (MAP), fetal heart rate (FHR), carotid artery blood flow (CaBF) and cortical laser Doppler flow (LDF) 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: Occlusion was associated with an initial increase in MAP, followed by a rapid fall below baseline values and ultimately with profound hypotension at all ages. MAP was significantly higher in the 0.85 group at baseline (43.3±1.3 vs. 35.6±0.6 and 36.4±0.6 mmHg in the 0.6 and 0.7 ga groups respectively, p<0.05) and for the first 6 minutes of occlusion compared to 0.6 and 0.7 ga fetuses (p<0.05). MAP was also significantly higher over the first 2–7 min in the 0.7 ga compared to the 0.6 ga group (p<0.05). The onset of hypotension occurred earlier with increasing gestation (Figure 1). MAP fell significantly below baseline at 8 min the 0.85 ga group, and 9 min in the 0.6 and 0.7 ga groups. FHR was significantly lower at baseline in the 0.85 ga group compared to the 0.6 and 0.7 ga groups (178±5 bpm vs. 191±3 bpm in both 0.6 and 0.7 ga groups, p<0.05). Occlusion was associated with rapid bradycardia followed by a similar gradual further fall in all groups.

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