Delayed hypotension and subendocardial injury after repeated umbilical cord occlusion in near-term fetal lambs

Gunn, Alistair J.; Maxwell, Linda; Haan, Harmen H. de; Bennet, Laura; Williams, Christopher E.; Gluckman, Peter D.; Gunn, Tania R.

doi:10.1067/mob.2000.108084

Cited by 49 publications

(47 citation statements)

References 17 publications

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“…This combination of findings strongly implies that cardiac contractility was impaired, with MAP supported by peripheral vasoconstriction. This is consistent with previous findings of increased plasma troponin T levels after 15 min of complete UCO [36], [40], and reversible sub-endocardial injury after prolonged brief repeated UCO in term-equivalent fetal sheep [41]. It is interesting to note that despite this, fetuses were able to maintain spontaneous peripheral vasoconstriction for at least 3 days after this very severe insult.…”

Section: Discussionsupporting

confidence: 92%

Status Epilepticus after Prolonged Umbilical Cord Occlusion Is Associated with Greater Neural Injury Fetal Sheep at Term-Equivalent

et al. 2014

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The majority of pre-clinical studies of hypoxic-ischemic encephalopathy at term-equivalent have focused on either relatively mild insults, or on functional paradigms of cerebral ischemia or hypoxia-ischemia/hypotension. There is surprisingly little information on the responses to single, severe ‘physiological’ insults. In this study we examined the evolution and pattern of neural injury after prolonged umbilical cord occlusion (UCO). 36 chronically instrumented fetal sheep at 125–129 days gestational age (term = 147 days) were subjected to either UCO until mean arterial pressure was < = 8 mmHg (n = 29), or sham occlusion (n = 7). Surviving fetuses were killed after 72 hours for histopathologic assessment with acid-fuchsin thionine. After UCO, 11 fetuses died with intractable hypotension and 5 ewes entered labor and were euthanized. The remaining 13 fetuses showed marked EEG suppression followed by evolving seizures starting at 5.8 (6.8) hours (median (interquartile range)). 6 of 13 developed status epilepticus, which was associated with a transient secondary increase in cortical impedance (a measure of cytotoxic edema, p<0.05). All fetuses showed moderate to severe neuronal loss in the hippocampus and the basal ganglia but mild cortical cell loss (p<0.05 vs sham occlusion). Status epilepticus was associated with more severe terminal hypotension (p<0.05) and subsequently, greater neuronal loss (p<0.05). In conclusion, profound UCO in term-equivalent fetal sheep was associated with delayed seizures, secondary cytotoxic edema, and subcortical injury, consistent with the predominant pattern after peripartum sentinel events at term. It is unclear whether status epilepticus exacerbated cortical injury or was simply a reflection of a longer duration of asphyxia.

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Section: Discussionsupporting

confidence: 92%

Status Epilepticus after Prolonged Umbilical Cord Occlusion Is Associated with Greater Neural Injury Fetal Sheep at Term-Equivalent

et al. 2014

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“…There is no evidence for continuing reflex mechanisms at this time (1). Likely contributors to impaired cardiac function include hypoxia, acidosis, depletion of myocardial glycogen, and cardiomyocyte injury (24). It is notable that after resolution of the initial hypertension, the fall in blood pressure in the second half of occlusion slowed to a steady pace of around 1 mmHg per minute, in parallel with the continued fall in heart rate.…”

Section: Discussionmentioning

confidence: 97%

Male disadvantage? Fetal sex and cardiovascular responses to asphyxia in preterm fetal sheep

Booth¹,

Ahmed-Nasef²,

Dean³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Clinically and experimentally male fetuses are at significantly greater risk of dying or suffering injury at birth, particularly after premature delivery. We undertook a retrospective cohort analysis of 60 female and 65 male singleton preterm fetal sheep (103-104 days, 0.7 gestation) with mean arterial blood pressure (MAP), heart rate, and carotid and femoral blood flow recordings during 25 min of umbilical cord occlusion in utero. Occlusions were stopped early if fetal MAP fell below 8 mmHg or if there was asystole for >20 s. Fetuses that were able to complete the full 25-min period of occlusion showed no differences between sexes for any cardiovascular responses. Similar numbers of occlusions were stopped early in males (mean: 21 min, n = 16) and females (mean: 23 min, n = 16); however, they showed different responses. Short-occlusion males (n = 16) showed a slower initial fall in femoral vascular conductance, followed by greater bradycardia, hypotension, and associated organ hypoperfusion compared with full-occlusion fetuses. In contrast, short-occlusion females (n = 16) showed a significantly more rapid early increase in femoral vascular conductance than the full-occlusion fetuses, followed by worsening of bradycardia and hypotension that was intermediate to the full-occlusion fetuses and short-occlusion males. Among all fetuses, MAP at 15 min of occlusion, corresponding with the time of the maximal rate of fall, was correlated with postmortem weight in males (R(2) = 0.07) but not females. In conclusion, male and female fetuses showed remarkably similar chemoreflex and hemodynamic responses to severe asphyxia, but some males did show impaired hemodynamic adaptation within the normal weight range.

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“…Loss of peripheral vasoconstriction was associated with a further, progressive fall in heart rate, and, after ϳ6 min, with overt hypotension. There is no evidence for continuing reflex mechanisms at this time (3); likely contributors to impaired cardiac function include hypoxia, acidosis, depletion of myocardial glycogen, and cardiomyocyte injury (17).…”

Section: Discussionmentioning

confidence: 99%

Preexisting hypoxia is associated with a delayed but more sustained rise in T/QRS ratio during prolonged umbilical cord occlusion in near-term fetal sheep

Wibbens

Westgate²,

Haan³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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There is limited information about whether preexisting fetal hypoxia alters hemodynamic responses and changes in T/QRS ratio and ST waveform shape during subsequent severe asphyxia. Chronically instrumented near-term sheep fetuses (124 +/- 1 days) were identified as either normoxic Pa(O(2)) > 17 mmHg (n = 9) or hypoxic Pa(O(2)) < or = 17 mmHg (n = 5); then they received complete occlusion of the umbilical cord for 15 min. Umbilical cord occlusion led to sustained bradycardia, severe acidosis, and transient hypertension followed by profound hypotension in both groups. Preexisting hypoxia did not affect changes in mean arterial blood pressure but was associated with a more rapid initial fall in femoral blood flow and vascular conductance and with transiently higher fetal heart rate at 2 min and from 9 to 11 min of occlusion compared with previously normoxic fetuses. Occlusion was associated with a significant but transient rise in T/QRS ratio; preexisting hypoxia was associated with a significant delay in this rise (maxima 3.7 +/- 0.4 vs. 6.2 +/- 0.5 min), but a slower rate of fall. There was a similar elevation in troponin-T levels 6 h after occlusion in the two groups [median (range) 0.43 (0.08, 1.32) vs. 0.55 (0.16, 2.32) microg/l, not significant]. In conclusion, mild preexisting hypoxia in normally grown singleton fetal sheep is associated with more rapid centralization of circulation after umbilical cord occlusion and delayed elevation of the ST waveform and slower fall, suggesting that chronic hypoxia alters myocardial dynamics during asphyxia.

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Delayed hypotension and subendocardial injury after repeated umbilical cord occlusion in near-term fetal lambs

Cited by 49 publications

References 17 publications

Status Epilepticus after Prolonged Umbilical Cord Occlusion Is Associated with Greater Neural Injury Fetal Sheep at Term-Equivalent

Status Epilepticus after Prolonged Umbilical Cord Occlusion Is Associated with Greater Neural Injury Fetal Sheep at Term-Equivalent

Male disadvantage? Fetal sex and cardiovascular responses to asphyxia in preterm fetal sheep

Preexisting hypoxia is associated with a delayed but more sustained rise in T/QRS ratio during prolonged umbilical cord occlusion in near-term fetal sheep

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