Partial Occlusion Of Umbilical Cord Research Articles

When should foetal pH measurements be performed after a prolonged deceleration? An experimental study in a fetal sheep model

ObjectiveThe aim of fetal heart rate monitoring during labour is to identify and prevent foetal distress, but its evaluation is not perfect. Fetal scalp blood sampling for pH measurement is one of the second-line methods of monitoring when fetal heart rate is classified as suspicious. This study aims to determine when pH testing should be performed after a prolonged deceleration. Study designThis was an experimental study in a fetal sheep model. A partial umbilical cord occlusion was performed for seven minutes followed by a recuperation period of 30 min. Hemodynamic parameters (heart rate, mean blood pressure and intra-amniotic pressure) and blood gases were recorded before occlusion (T0), during occlusion (T4), just after the end of occlusion (T7), and then 10, 20 and 30 min after occlusion (T17, T27 and T37 respectively). ResultsTen experiments were carried out. During partial cord occlusion, the fetal pH decreased significantly to acidosis. After a prolonged deceleration with fetal acidosis, the pH recovered to a normal value, defined by a pH greater than or equal to 7.25, after 20 min of recuperation. ConclusionAfter a prolonged deceleration, fetal pH normalizes between 20 and 30 min thereafter. Thus, if a foetal blood sample is indicated, this delay must be respected in order to avoid inducing an unnecessary intervention decision.

Magnesium sulfate treatment decreases the initial brain damage alterations produced after perinatal asphyxia in fetal lambs

The aim of this work was to analyze the effect of MgSO(4) treatment in the brain after hypoxic-ischemic (HI) injury in premature fetal lambs. Injury was induced by partial occlusion of umbilical cord for 60 min, and then the preterm lambs (80-90% of gestation) were randomly assigned to one of the following groups: control group, in which the animals were managed by conventional mechanical ventilation for 3 hr; 3 hr postpartial cord occlusion (3-hr-PCO) group, in which injured animals were managed by ventilation and then sacrificed 3 hr after HI; and MgSO(4) group, in which animals received 400 mg/kg MgSO(4) for 20 min soon after HI was induced and were managed by ventilation for 3 hr. Brains were analyzed for apoptosis by TUNEL assay. Cell viability and intracellular state studies were assessed by flow cytometry. The delayed death index was significantly increased in the 3-hr-PCO group in comparison with control. Administration of MgSO(4) elicited a delay in cell death that was similar to that in the control group. The 3-hr-PCO group showed a significantly higher concentration of reactive oxygen species, mitochondrial damage, and intracellular calcium in comparison with control and MgSO(4) - treated groups. Our results suggest that MgSO(4) treatment might have potential therapeutic benefits after the HI event.

305 Regional Cerebral Blood Flow in Asphyctic Foetal Lambs after Rescue with MgSO4

Background: Hypoxic-ischemic (HI) injury induced by partial cord clamping produces brain damage. MgSO4 infusion has been used as a neuroprotector, but it produces haemodynamic and cardiac changes.Aim: To determine the effects of MgSO4 infusion on cerebral oxygenation, cardiovascular parameters and regional cerebral flow (RCBF) in preterm lambs with perinatal asphyxia induced by umbilical cord occlusion.Methods: 18 preterm lambs (80–90% GE) were used. Lambs were randomly assigned to receive magnesium sulphate (MGSO4) or not (SHAM) after HI injury induced by partial cord clamping. Non-injured group was used as (CONTROL). Carotid blood flow (CBF), systemic arterial pressure (SAP), heart rate (HR), arterial oxygen content (CaO2) and O2-uptake were measured. RCBF by microspheres and previous parameters were determined at fetal point (F), post-injury (P-I), 1h and at the end of the experiment. Frontal, parietal, temporal and occipital cortex were grouped (C), and striatum, thalamus, hypothalamus and hippocampus as periventicular zones (P). One factor ANOVA, p<0.05Results: After injury, H-I injured groups developed acidosis, hypoxia and hypercapnia in comparison with control group. Also, they demonstrated an increase in HR without change on SAP. MgSO4 infusion did not showed significant changes in SAP, HR, CBF and O2-uptake in comparison with other groups.Conclusion: In our model of perinatal asphyxia by partial occlusion of umbilical cord in premature foetal lambs, MgSO4 infusion does not compromise the cardiovascular adaptation to asphyxia. However, histopathological analysis of brain tissue and neuronal metabolic status must be study to evaluate the neuroprotective effect of MgSO4. Supported by grants: FIS 03/987 and RESPIRA net of RITC, FIS C03/11.

244 Brain Mitochondrial Membrane Damage After Asphyxia in Foetal Lambs

Background: Mitochondria play a crucial role as the main intracellular source of energy. Mitochondria contain cardiolipin, a phospholipid mainly located in the internal membrane of these organelles, which is essential for the functionality of several mitochondrial proteins and is important for ATP synthesis.Aim: To analyse morphofunctional alterations that occur at the mitochondrial level in a perinatal asphyxia model induced by partial umbilical cord occlusion in foetal lambs. Methods: 15 foetal lambs (80–90% GE) were used. Asphyxia was performed by partial occlusion of umbilical flow during 1h. Lambs were randomly assigned to: Control group, lambs were sacrificed immediately (0h), or managed on intermittent mandatory ventilation (IMV) for 3h; Hipoxic-isquemic (H-I) group, lambs were sacrificed immediately after asphyxia (0h) or managed on IMV for 3h. Mitochondrial membrane damage was determined by measuring the concentration of cardiolipin using the fluorochrome nonyl acridine orange (NAO) by flow cytometry. Cerebral regions were divided into: Cortex, inner zones (striatum, thalamus, hypothalamus, hippocampus), cerebellum and pons. One-factor ANOVA, p<0.05.Results: Cell stained percentage is summarised in the table:(*)vs. all groupTable 1Full size tableConclusion: In H-I animals, we can observe a significant decrease in the mitochondrial viability after 3h of resuscitation. Mitochondrial alteration is an early finding of cell damage in brain of asphyctic animals.Supported by grants: FIS PI03/0987 and RESPIRA net of RITC, FIS C03/11

Effect of prolonged asphyxia on skin blood flow in fetal lambs

Objective: To determine the effect of a prolonged period of asphyxia on skin blood flow, a potential indicator of fetal cardiovascular responses to asphyxia, in the chronically catheterized fetal lamb. Methods: Eight chronically instrumented pregnant ewes were studied at 118 ± 1 days’ gestation. After a control period, fetal acid-base status was assessed and regional blood flows were determined with dye-labeled microspheres. Fetal asphyxia was then induced by partial umbilical cord occlusion, decreasing fetal arterial oxygen pressure to 15 torr while maintaining pH above 7.28. Fetal cardiovascular status was monitored continuously. Fetal acid base status was evaluated every 10–15 minutes during cord occlusion. Regional blood flow determinations were repeated after 90 minutes of stable asphyxia. Results are expressed as the mean ± standard error. Student t test for paired data was used to compare hemodynamic, acid-base, and regional blood flow determinations before cord occlusion and after 90 minutes of asphyxia. Results: There was a significant increase in blood flow to the fetal scalp from a control value of 52 ± 8 mL per minutes per 100 g to 175 ± 30 mL per minute per 100 g at 90 minutes of asphyxia ( P = .01). Similarly, there was an increase in blood flow to the skin overlying the fetal hindquarter from 39 ± 12 mL per minute per 100 g during control to 153 ± 47 mL per minute per 100 g at asphyxia ( P = .038). Conclusion: In the chronically instrumented fetal lamb, a 90-minute period of asphyxia produced by partial cord occlusion resulted in a significant increase in blood flow to the fetal skin.

Histologic and biochemical study of the brain, heart, kidney, and liver in asphyxia caused by occlusion of the umbilical cord in near-term fetal lambs

Objective: We sought to determine the relationship between the degree of histologic changes in the brain, heart, kidney, and liver in fetal lambs after severe asphyxia and to analyze the role of oxidative stress in the pathogenesis of fetal multiple organ failure. Study Design: Eight chronically instrumented near-term fetal lambs were asphyxiated by partial umbilical cord occlusion for approximately 60 minutes until the fetal arterial pH reached <6.9 and the base excess reached <–20 mEq/L. An additional 6 fetuses were used as sham-asphyxiated controls. Fetal heart rates, blood pressure, fetal breathing movements, and arterial blood gases and acid-base states were serially monitored. The brain, heart, kidney, and liver were collected 72 hours after asphyxia, processed, and histologically examined after hematoxylin and eosin staining. Fetal brain histologic features were classified into 5 grades, with 5 being the most severe damage. The other organs were examined histologically by pathologists who were blinded to the treatment. Each organ was assayed for tissue concentrations of thiobarbituric acid–reactive substances, superoxide dismutase, glutathione, lactate, and glucose. Results: Myocardial changes of necrosis, phagocytosis, and contraction bands occurred in only 2 of the most severely (grade 5) brain-damaged fetuses. The same 2 cases showed fatty changes and congestion in the liver. In the kidney all asphyxiated cases showed tubular necrosis, but glomeruli were generally spared. Of the measures of oxidative stress, only liver tissue levels of thiobarbituric acid–reactive substances and superoxide dismutase were significantly higher in the asphyxiated group than in the control group, but there was no correlation with the degree of damage. Lactate level was higher only in the heart in the asphyxiated fetuses. Conclusion: Renal tubular damage was seen with all degrees of asphyxia, despite variable brain damage. Histologic changes in the myocardium and liver were seen only with the most severe brain damage. Oxidative stress appears to play a role in the pathogenesis of liver damage. (Am J Obstet Gynecol 2000;182:449-57.)

Brain lipid peroxidation and antioxidant levels in fetal lambs 72 hours after asphyxia by partial umbilical cord occlusion

OBJECTIVES: The purpose of this study was to explain the role of oxidative stress in the pathogenesis of brain damage caused by intrauterine fetal asphyxia. STUDY DESIGN: Six chronically instrumented near-term fetal lambs were subjected to asphyxia by partial umbilical cord occlusion for approximately 60 minutes until fetal arterial pH diminished to less than 6.9 and base excess to less than –20 mEq. Another six fetuses surgically prepared but not occluded were used as control. Fetuses were killed after 72 hours and eight different brain regions (frontal and parietal gray matter, frontal and parietal white matter, basal ganglia, thalamus, hippocampus, and cerebellum) were dissected and assayed for thiobarbituric acid reactive substances, glutathione, and superoxide dismutase. RESULTS: Thiobarbituric acid reactive substance levels in asphyxiated animals were elevated in frontal and parietal white matter, basal ganglia, and thalamus compared with those in controls. The concentrations of superoxide dismutase in the asphyxiated group were also higher in frontal and parietal white matter, basal ganglia, and cerebellum compared with those in the control group. Between the two groups, however, glutathione concentrations did not differ significantly. CONCLUSION: These results suggest that oxidative stress may be a major contributing factor to the development of brain damage in intrauterine fetal asphyxia. (Am J Obstet Gynecol 1998;178:474-8.)

Physiologic and histologic changes in near-term fetal lambs exposed to asphyxia by partial umbilical cord occlusion

OBJECTIVE: Our purpose was to characterize the histologic changes in the asphyxiated fetal lamb brain and to correlate the severity of these changes with fetal physiologic parameters during and after asphyxia. STUDY DESIGN: Seventeen near-term fetuses were used for analysis: control group without manipulation ( n = 4, 132 ± 1.1 days of gestation at autopsy, mean ± SEM), sham-asphyxia control group ( n = 3, 132 ± 1.3 days), and asphyxiated group, which successfully survived 72 hours after asphyxia ( n = 10, 130 ± 1.0 days). Asphyxia was produced by umbilical cord occlusion lasting for approximately 60 minutes until fetal arterial pH diminished to <6.9 and base excess to <-20 mEq/L. Fetal heart rate, blood pressure, and electrocorticographic activity were continuously monitored. The fetuses were killed 72 hours after asphyxia, and the brains were fixed in formalin and processed for histologic and immunocytochemical studies. RESULTS: Neuropathologic changes varied from case to case, ranging from almost total infarction of cortical and subcortical structures to extremely subtle and patchy white matter alterations characterized by slight vacuolization of the white matter or slight to moderate increases in cellularity confined to the junction of cerebral cortex and white matter. Even fetuses that showed full recovery of all physiologic parameters, including electrocorticographic activity, demonstrated subtle but distinct white matter lesions. The gray matter, including the hippocampal neurons, was generally spared in these cases. Electrocorticographic parameters, duration of hypotension during asphyxia, and delayed recovery of blood lactate concentrations correlated well with the histologic grading of brain damage. CONCLUSIONS: Asphyxia by partial umbilical cord occlusion in near-term fetal lambs produces variable neuropathologic changes. The mildest change is a white matter lesion characterized by vacuolization and loss of myelin or by increased cellularity in the damaged regions. (Am J Obstet Gynecol 1998;178:24-32.)

The effects of bupivacaine, L-nitro-L-arginine-methyl ester, and phenylephrine on cardiovascular adaptations to asphyxia in the preterm fetal lamb.

The preterm fetal lamb that is exposed to clinically relevant plasma concentrations of lidocaine loses its cardiovascular adaptations to asphyxia, and its condition deteriorates further. Nitric oxide (NO) is an important regulator of vascular tone, and local anesthetics are known to inhibit endothelium-dependent vasodilation. The purpose of the present study was to determine whether the adverse effects of lidocaine noted in the preterm fetal lamb also occur with bupivacaine and whether the inhibition of NO results in effects similar to those of bupivacaine. Thirty-two chronically prepared pregnant sheep were studied at 117-119 days' gestation. Maternal and fetal blood pressure, heart rate, and acid-base state were evaluated. Fetal organ blood flows were determined using 15-microM diameter dye-labeled microspheres. After a control period, mild to moderate asphyxia (fetal PaO2 15 mm Hg) was induced by partial umbilical cord occlusion and maintained throughout the experiment. Ewes in Group I (n = 13) were given a two-step intravenous infusion of bupivacaine for 180 min. Fetuses in Group II (n = 12) received an intravenous injection of L-nitro-L-arginine-methyl ester (L-NAME) (25 mg/kg), and measurements were taken 10 and 30 min after the injection. A third group (Group III) of fetuses (n = 7) were given an intravenous infusion of phenylephrine to mimic the blood pressure increases noted in L-NAME-treated fetuses. At 90 min of stable asphyxia, there was a significant decrease in fetal PaO2 and pHa and an increase in PaCO2 and mean arterial blood pressure. There was also an increase in blood flow to the adrenals, myocardium, and cerebral cortex, whereas blood flow to the placenta decreased. Administration of bupivacaine during asphyxia did not affect the changes in mean arterial blood pressure and acid-base state but did abolish the increases in blood flows to the myocardium and cerebral cortex. Injection of L-NAME to the asphyxiated fetus resulted in an increase in mean arterial blood pressure above the level noted at 90 min of cord occlusion, and an increase in fetal PaO2 toward control levels. This was accompanied by a reduction in organ blood flows to preasphyxia levels. In asphyxiated Group III fetuses, titration of the phenylephrine infusion to achieve blood pressure increases similar to those noted with L-NAME were also associated with an increase in fetal PaO2. These data indicate that bupivacaine abolishes some of the circulatory adaptations to mild to moderate asphyxia induced by partial cord occlusion in the preterm fetal lamb. It is not clear whether these effects of bupivacaine are due to inhibition of NO. In the preterm fetal lamb, clinically relevant plasma concentrations of bupivacaine achieved by intravenous infusion to the pregnant ewe (80% gestation) abolished some of the fetal cardiovascular adaptations to asphyxia induced by partial umbilical cord occlusion.

Physiological and histological changes in near term fetal lambs exposed to asphyxia by partial umbilical cord occlusion.

Physiological and histological changes in near term fetal lambs exposed to asphyxia by partial umbilical cord occlusion.

Regional blood flow and metabolism in ovine fetuses during severe cord occlusion

Our purpose was to compare the ovine fetal response to severe, damaging asphyxia resulting from umbilical cord occlusion with that seen in uterine artery occlusion. Six ovine fetuses were exposed to severe asphyxia produced by partial umbilical cord occlusion for 90 minutes. Fetal blood pressure and heart rate, blood gases, acid base status, electrocorticogram, and electromyogram were recorded. Regional blood flow (radioactive microspheres) measurements were performed at control and 30, 60, and 90 minutes of occlusion and 30 minutes after release. During the period of occlusion pH fell from 7.37 +/- 0.01 (mean +/- SEM) to 6.82 +/- 0.03 at 90 minutes, base excess from 5 +/- 1 to -22 +/- 2 mEq.L-1 and oxygen content from 3.3 +/- 0.4 mmol.L-1 to a nadir of 1.6 +/- 0.4 mmol.L-1 (p < 0.05). There was no significant long-term change in fetal heart rate or blood pressures. The fetal electrocorticogram was profoundly suppressed during asphyxia, and seizure activity was documented after release of occlusion in all surviving animals. Umbilical blood flow fell to 21% +/- 5% of control by 60 minutes of occlusion and remained depressed until release. Brain and adrenal blood flows increased during asphyxia. Heart and intestinal blood flows did not change significantly from control values. Combined ventricular output and spleen, kidney, and carcass blood flow fell during the insult. Oxygen uptake by the cerebral cortex remained stable during occlusion. Oxygen uptake by the lower carcass fell to 15% +/- 7% of control. Umbilical cord occlusion produces similar levels of asphyxia and evidence of encephalopathy (seizures), compared with previous experiments with uterine artery occlusion. The fetal response with respect to blood flow redistribution and organ oxygen uptake, however, differs. These differences may signify that with uterine artery occlusion the brain may be more vulnerable, whereas with umbilical cord occlusion the heart may be at greater risk.

Variable fetal heart rate decelerations and electrocortical activities

OBJECTIVE: The purpose of this study was to examine the influence of fetal behavioral states on baroreflex-mediated, variable fetal heart rate decelerations caused by umbilical cord occlusion. STUDY DESIGN: Five chronically instrumented fetal lambs were subjected to intermittent partial umbilical cord occlusion for 1 minute every 3 minutes, lasting 2 hours. Fetal behavioral states determined by electrocorticogram and heart rates by electrocardiogram were monitored continuously during these experiments. RESULTS: The fetuses exhibited an alteration between low- and high-voltage electrocorticogram states. Both the depth and width of the variable fetal heart rate decelerations were greater during high-voltage than during low-voltage electrocorticogram. CONCLUSION: Amplitude and duration of variable fetal heart rate decelerations are affected by fetal behavioral states. (AM J OBSTET GYNECOL 1994;170:689-92.)

Adverse effects of maternally administered lidocaine on the asphyxiated preterm fetal lamb.

Lidocaine was infused at a constant rate of 0.1 mg.kg-1.min-1 for 180 min into 12 chronically prepared pregnant sheep while asphyxia, induced by partial umbilical cord occlusion, was maintained in the premature fetus (80% of gestation). In five similar preparations saline instead of lidocaine was infused into the mother for 180 min. Maternal and fetal arterial blood pressure, heart rate, pHa, PaCO2, and PaO2 were monitored, and fetal cardiac output and the distribution of blood flow to fetal organs were measured, using labeled microspheres, before and after asphyxia and again after maternal infusion of lidocaine or saline. Maternal and fetal arterial blood and maternal urine were obtained at intervals for determination of lidocaine concentrations and urinary drug clearance. At the end of infusion, these animals were killed and tissues dissected for determination of lidocaine concentrations and organ blood flow. Maternal and fetal lidocaine plasma concentrations at steady state were 2.32 +/- 0.12 and 1.23 +/- 0.17 microgram/ml, respectively, similar to those seen during human epidural anesthesia. Asphyxia resulted in a significant drop in fetal heart rate and increased blood flow to the brain, heart, and adrenals. Asphyxia and saline did not produce additional deterioration of the fetus, but asphyxia and lidocaine led to a significant increase in PaCO2 and decreases in pHa, mean arterial pressure, and blood flows to the brain, heart, and adrenals. It is concluded that the immature fetus loses its cardiovascular adaptation to asphyxia when exposed to clinically acceptable plasma concentrations of lidocaine obtained transplacentally from the mother.