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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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Concentration changes in ΔHb (HbO2-Hb), THb (HbO2+Hb) and oxidized cytochrome oxidase (CytOx) during occlusion.Data are one minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; o: p<0.05 for 0.6 vs. 0.7 and 0.85 groups; *: p<0.05 for 0.6 vs. 0.7 groups; δ: p<0.05 for 0.7 vs. 0.85 groups.
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pone-0039273-g003: Concentration changes in ΔHb (HbO2-Hb), THb (HbO2+Hb) and oxidized cytochrome oxidase (CytOx) during occlusion.Data are one minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; o: p<0.05 for 0.6 vs. 0.7 and 0.85 groups; *: p<0.05 for 0.6 vs. 0.7 groups; δ: p<0.05 for 0.7 vs. 0.85 groups.

Mentions: Occlusion was associated with a rapid, profound fall in ΔHb. This fall was greater with increasing gestation (Figure 3), reaching a nadir of −34.0±4.2 µM in the 0.6 group, −42.7±1.7 µM in the 0.7 group, and −47.6±2.4 µM in the 0.85 group (p<0.05). After the nadir there was an apparent increase in ΔHb over the remainder of occlusion in all groups, mediated by a proportionately greater fall in Hb than HbO2; HbO2 did not increase (data not shown). THb initially increased during the compensation phase with a greater rise with increasing gestation, reaching a maxima of 4.7±1.6 µM at 6 min in the 0.6 group, 9.2±0.9 µM at 7 min in the 0.7 group, and 6.0±1.2 µM at 4 min in the 0.85 group (p<0.05, Figure 3). This was followed by a fall in THb in all groups; this fall began earlier in the 0.85 group and was significantly lower than the preterm groups from 6–10 min (p<0.05). Subsequent THb fell in all three groups in parallel, with similar values from around 11 min until the end of their respective occlusion (Figure 3).


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)

Concentration changes in ΔHb (HbO2-Hb), THb (HbO2+Hb) and oxidized cytochrome oxidase (CytOx) during occlusion.Data are one minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; o: p<0.05 for 0.6 vs. 0.7 and 0.85 groups; *: p<0.05 for 0.6 vs. 0.7 groups; δ: p<0.05 for 0.7 vs. 0.85 groups.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0039273-g003: Concentration changes in ΔHb (HbO2-Hb), THb (HbO2+Hb) and oxidized cytochrome oxidase (CytOx) during occlusion.Data are one minute mean±S.E.M. Δ: p<0.05 for 0.85 vs. 0.6 and 0.7 groups; o: p<0.05 for 0.6 vs. 0.7 and 0.85 groups; *: p<0.05 for 0.6 vs. 0.7 groups; δ: p<0.05 for 0.7 vs. 0.85 groups.
Mentions: Occlusion was associated with a rapid, profound fall in ΔHb. This fall was greater with increasing gestation (Figure 3), reaching a nadir of −34.0±4.2 µM in the 0.6 group, −42.7±1.7 µM in the 0.7 group, and −47.6±2.4 µM in the 0.85 group (p<0.05). After the nadir there was an apparent increase in ΔHb over the remainder of occlusion in all groups, mediated by a proportionately greater fall in Hb than HbO2; HbO2 did not increase (data not shown). THb initially increased during the compensation phase with a greater rise with increasing gestation, reaching a maxima of 4.7±1.6 µM at 6 min in the 0.6 group, 9.2±0.9 µM at 7 min in the 0.7 group, and 6.0±1.2 µM at 4 min in the 0.85 group (p<0.05, Figure 3). This was followed by a fall in THb in all groups; this fall began earlier in the 0.85 group and was significantly lower than the preterm groups from 6–10 min (p<0.05). Subsequent THb fell in all three groups in parallel, with similar values from around 11 min until the end of their respective occlusion (Figure 3).

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