Delayed intrauterine repair of an experimental spina bifida with a collagen biomatrix.

BACKGROUND/PURPOSE: The aim of the study was to evaluate whether a collagen biomatrix is useful for delayed intrauterine coverage of a surgically created spina bifida in a fetal lamb. METHODS: In 20 fetal lambs, surgery was performed at 72 or 79 days' gestation. In 15 lambs a spina bifida was created surgically. In 8 lambs it was covered with a collagen biomatrix 2 weeks later and in 7 lambs it was left uncovered. Five lambs served as sham operated controls. Neurological examination was performed at 1 week of age and afterwards the lambs were sacrificed for further histological evaluation. RESULTS: None of the 5 surviving lambs with the defect covered showed loss of spinal function and the architecture of the spinal cord was preserved in 4 of the 5 lambs. In the uncovered group, 1 of the 4 surviving lambs had loss of spinal function, 5 lambs were available for histological evaluation and 4 of them showed disturbance of the architecture of the spinal cord. CONCLUSIONS: Collagen biomatrices can be used for intrauterine coverage of an experimental spina bifida and can preserve the architecture of the spinal cord. Neurological outcome is not different between fetuses with their spinal cord covered and fetuses with uncovered cords.

Histological evaluation of acute covering of an experimental neural tube defect with biomatrices in fetal sheep.

OBJECTIVE: The aim of the study was to determine the histological effect on the neural tissue of in utero covering of an experimental neural tube defect in fetal lambs, with the use of two different biomatrices. MATERIALS AND METHODS: In 23 fetal sheep, surgery was performed at 79 days' gestation. In 19 of these, a neural tube defect was created, while 4 fetuses served as sham-operated controls. In 7 of the 19 operated fetuses the defect was left uncovered. In the remaining 12 animals the defect was covered either with a collagen biomatrix (4 animals), skin (3 animals), or small intestinal submucosa biomatrix (5 animals). The lambs were sacrificed at 1 week of age and histological examination was performed. RESULTS: All lambs with an uncovered neural tube defect showed histological damage of the spinal cord. In lambs in which the neural tube defect was covered, one half showed a normal architecture of the spinal cord while minor histological damage was present in the other half. Between the three groups in which the defect was covered, the histological outcome was comparable. CONCLUSIONS: Acute covering of an experimental neural tube defect in fetal lambs prevents severe histological damage to the spinal cord independent of the two biomatrices used in this study.

In utero repair of an experimental neural tube defect in a chronic sheep model using biomatrices.

OBJECTIVE: Persistent exposure of the unprotected spinal cord to amniotic fluid and the uterine wall can lead to progressive damage of neural tissue in case of a myelomeningocele (two-hit hypothesis). The aim of this study was to evaluate whether in utero repair of an experimental neural tube defect in a fetal lamb could protect neural tissue from secondary injury and save neurologic functions after birth. METHODS: In 19 fetal lambs, a neural tube defect was created at 79 days' gestation. In 12 lambs the defect was covered either with a novel, molecular defined collagen-based biocompatible and biodegradable matrix (UMC) or with a small intestinal submucosa (SIS) biomatrix (Cook) or by closing the skin over the defect. RESULTS: All lambs with the defect covered showed no or minor neurologic morbidity in contrast to the lambs with the defect uncovered in which major neurologic morbidity was seen. CONCLUSIONS: These results demonstrate that long-term exposure of the open spinal cord to the intrauterine environment can lead to damage of neural tissue and, consequently loss of neurologic functions and that coverage of the defect can lead to a better neurologic outcome. Furthermore, we could show that a UMC biomatrix and an SIS biomatrix are useful for in utero coverage of a surgically created neural tube defect in our model.

Effects of chronic hyperglycemia on electrocortical activity states in unanesthetized fetal lambs.

Electrocortical activity (ECoG), tracheal pressure and nuchal muscle activity were recorded in utero in 8 chronically hyperglycemic and 10 control unanesthetized fetal lambs to investigate the effects of chronic hyperglycemia on fetal electrocortical activity states. The chronically hyperglycemic state, induced by alloxan administered to the ewes, existed for at least 40 days prior to the experiments. The mean duration of episodes of high voltage (HV) ECoG was significantly increased in the hyperglycemic group (mean +/- SD: 21.8 +/- 9.2 min) compared with the control group (14.8 +/- 3.3 min), but the incidence of low voltage (LV) ECoG was not different between the groups. ECoG power spectra were not different between the groups. During LV ECoG, the proportions of time with neck movements were significantly less in the hyperglycemic than in the control group. No difference in percentages of time with long neck muscle activity was seen during the HV state in both groups. The incidence of breathing movements was equal in both groups, during HV as well as LV ECoG. No differences in breathing interval were observed.

Variability of the ECG waveform in fetal and neonatal lambs.

Changes in the waveform of the fetal electrocardiogram (FECG) are being investigated by several groups for its clinical significance with regard to the assessment of fetal condition. During our experiments with fetal lambs we frequently observed spontaneous FECG waveform changes, also during steady state in control animals. From the examples presented we conclude that the FECG waveform can be very sensitive to changes in the electrode position relative to the fetal heart. Such changes can easily be caused by fetal movements. ECG leads with a minimal sensitivity to these effects should be selected.

The influence of long term beta-mimetic drug administration during pregnancy on blood loss postpartum.

Early blood loss after-delivery was measured in all prematurely ending singleton pregnancies (amenorrhea 29-38 wk) during which the patients had been treated with beta-mimetics (ritodrine or fenoterol) for the prevention of premature labor, during a 4 yr study period (1975--1978) (n = 129). For comparison, postpartum blood loss was measured in the same way in all other (not treated) patients who delivered with the same gestational ages during the first 2 yr of the investigation (n = 176). Only vaginal deliveries were included and some patient categories were excluded. Placental weight and episiotomy status were found to effect the amount of early postpartum blood loss at a significant level. Blood loss after delivery was found not to be increased by chronic beta-mimetic treatment, even when this treatment ended less than 24 h before delivery. Moreover, when the treatment--delivery interval exceeded 24 h, the average amount of blood loss by treated patients was less than that of the untreated patients in some comparison categories. No difference in the amount of blood loss was found according to the specific drug that had been used.

The preejection period of the fetal cardiac cycle. I. Umbilical cord occlusions.

The preejection period (PEP) of the fetal cardiac cycle was studied in the chronically instrumented fetal lamb. A specially constructed device permitted the occlusion of either both umbilical veins, or of both umbilical arteries, or of the total umbilical cord. A prolongation of the PEP together with an increase in blood pressure was a consistent finding during any type of cord occlusion. In poorly oxygenated fetal lambs a two-step increase in the duration of the PEP was observed during the occlusion. It was accompanied by a simultaneous two-step increase in fetal arterial blood pressure. A correlation was found between the steady-state fetal pO2 before the occlusion and the increase in fetal arterial diastolic blood pressure during the blockade of the umbilical circulation. During occlusion the main determining factors of the PEP prolongation appear to be the increase in afterload and the decrease in preload of the fetal heart. The second step in the prolongation of the PEP during the occlusions in poorly oxygenated fetal lambs is attributed to a chemoreceptor-induced reflex, resulting in a redistribution of cardiac output in the fetal lamb.

The preejection period of the fetal cardiac cycle. II. Maternal common internal iliac artery occlusions.

The preejection period (PEP) of the fetal cardiac cycle was studied in the chronically instrumented fetal lamb. An inflatable cuff occluder was positioned around the maternal common internal iliac artery, the pregnant ewe's main uterine blood-supplying vessel. Occlusion of the maternal common internal iliac artery produced a fall in pO2 and pH and a rise in pCO2. Fetal arterial blood pressure increased and PEP shortened, especially in the longer lasting occlusions. Fetal heart rate exhibited a bradycardia also during this type of occlusion. The fetal lamb's cardiovascular adjustments to biochemical changes caused by occlusion of the maternal uterine blood supply appear to be determined during the initial phase of occlusion by a chemoreceptor reflex-induced peripheral vasoconstriction mediated by the adrenergic nervous system. The condition is comparable to the one observed during the second part of the umbilical cord occlusions. The interaction between a supersensitive fetal myocardium and the adrenal release of catecholamines may play a dominant role during the second part of occlusion in the longer lasting experiments. Increase in peripheral resistance in the course of redistribution of blood flow during hypoxemia induces a prolongation of the PEP in the early phase of occlusion; overriding of this effect by an increase in myocardial contractility due to rising levels of adrenal catecholamines abbreviates the PEP in the later part of the longer lasting occlusions.