Effect of intrauterine inflammation on fetal cerebral hemodynamics and white-matter injury in chronically instrumented fetal sheep

Saito, Masatoshi; Matsuda, Tadashi; Okuyama, Kazuhiko; Kobayashi, Yoshiyasu; Kitanishi, Ryuta; Hanita, Takushi; Okamura, Koji

doi:10.1016/j.ajog.2009.01.006

Cited by 19 publications

(30 citation statements)

References 25 publications

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“…The preparations for this experiment were very similar to those used in our previous studies (13)(14)(15)(16). In brief, a total of five Suffolk ewes with timed pregnancies underwent surgery between 120 and 130 d of gestation.…”

Section: Animal Preparationmentioning

confidence: 99%

Novel modification of an artificial placenta: pumpless arteriovenous extracorporeal life support in a premature lamb model

et al. 2012

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Background: Previous studies aimed at developing an artificial placenta have had limited success. We hypothesized that the introduction of a high-performance membranous oxygenator to a pumpless artificial placenta could prolong the survival time of premature lambs. Methods: Immediately after delivery of the fetuses, the umbilical vessels were cannulated and connected to the pumpless artificial placenta. Both the fetuses and the circuit were submerged in a warm saline bath. results: Five fetuses survived for 18.2 ± 3.2 (mean ± seM) h after attachment to the artificial placenta, which maintained fetal circulation. circuit blood flow was positively correlated with mean arterial pressure and negatively correlated with blood lactate levels. Milrinone administration transiently decreased lactate levels, although dopamine administration unexpectedly induced a marked increase in the lactate levels despite an elevated arterial pressure and improved circuit blood flow. conclusIon: We prolonged the survival of fetal lambs using a high-performance membranous oxygenator with a small priming volume. The increased systemic resistance induced by vasoconstrictors may increase the circuit blood flow excessively, resulting in circulation failure in systemic organs; therefore, vasodilators may be more useful than vasoconstrictors for maintaining organ blood flow within this circuit.d espite progress in neonatal intensive care, effective treatments for premature low-birth-weight infants with cardiopulmonary abnormalities are lacking. The use of an artificial placenta has been proposed, but previous studies have had limited success, possibly because the circuit volume was too large and the resistance of the circuit was too high (1-5). A more compact circuit may be a solution; in 2009, Reoma et al. reported a 4-h survival period using a pumpless artificial placenta for the first time (6). However, the fetuses could not survive for longer than 4 h because of fetal circulatory deterioration. The authors concluded that prolonging the survival time any further was difficult without the assistance of a roller pump.Is it impossible to prolong the survival time using a pumpless artificial placenta? The goal of our study was to prolong survival time by improving the following two points. First, we developed a high-performance membranous oxygenator jointly with the group of A. Funakubo, who is a pioneer in the development of the membranous oxygenator (7,8). Our membranous oxygenator enabled a reduction in priming volume of 40%, as compared with that used in Reoma's experiment (6), while maintaining membrane surface area. Second, we administered a vasodilator to the fetuses to maintain circulation in systemic organs. Table 1 compares the values obtained in Reoma's experiments (6) with those obtained in our study. The fetuses in our experimental group had a shorter gestational age, a lower birth weight, and a longer survival time than those in Reoma's experiment. In this study, five fetuses were successfully connected to the artificial placenta,...

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Section: Animal Preparationmentioning

confidence: 99%

Novel modification of an artificial placenta: pumpless arteriovenous extracorporeal life support in a premature lamb model

et al. 2012

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“…Lower cerebral vascular resistance, vasodilatation, higher CBF velocities, and increased incidence of intracranial hemorrhage were observed in babies with early-onset neonatal sepsis (70). Hemodynamic disturbance and subsequent cerebral white matter injury are observed in preterm lambs that have been exposed to inflammatory stimuli and that mount a systemic inflammatory response (58,71,72). Thus, we suggest a progressive series of events that begins with initiation of suboptimal ventilation, which in turn stimulates a systemic proinflammatory cascade and may then directly result in inflammation-induced white matter injury or indirectly cause white matter injury through initiation of hemodynamic instability.…”

Section: Inflammatory Consequences Of the Initiation Of Respiratory Smentioning

confidence: 99%

Respiratory support for premature neonates in the delivery room: effects on cardiovascular function and the development of brain injury

et al. 2014

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“…As the experimental materials, we used fetal brain tissues obtained through following more or less the same protocols as reported from our previous two experiments (Matsuda et al 2006;Saito et al 2009). The hemorrhage group tissue samples were obtained from PVL induced by acute blood withdrawal (Matsuda et al 2006) and those in the other three groups, namely the sham group, the inflammation group and the inflammatory hemorrhage group, tissues were obtained from PVL related to intrauterine inflammation (Table 1 and Fig.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously developed two ovine model systems for studying fetal WMI: a PVL model with acute blood withdrawal and a PVL model of intrauterine inflammation (Matsuda et al 2006;Saito et al 2009). In the PVL model with acute blood withdrawal, about 40% of the fetoplacental blood volume was acutely withdrawn to generate ischemia-reperfusion injury in the deep cerebral white matter (Matsuda et al 2006).…”

Section: Introductionmentioning

confidence: 99%

“…This model thus mimics the placental abruption or placenta previa that is associated with fetal cerebral WMI. In the PVL model with intrauterine inflammation, intravenous granulocyte-colony stimulating factor (G-CSF) and intra-amniotic endotoxin were used to induce PVL lesions and multiple hemorrhagic necrotic lesions in the subcortical white matter (Saito et al 2009). This experimental system thus models fetal cerebral WMI induced by strong and chronic inflammation in utero, such as that seen in association with necrotizing funisitis and chorioamnionitis.…”

Section: Introductionmentioning

confidence: 99%

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Cerebral Ischemia or Intrauterine Inflammation Promotes Differentiation of Oligodendroglial Precursors in Preterm Ovine Fetuses: Possible Cellular Basis for White Matter Injury

Kitanishi

Matsuda

Watanabe

et al. 2014

Tohoku J. Exp. Med.

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White matter injury in premature infants is known to be major cause of long-term neurocognitive disability, but the pathogenic mechanism remains unclear, hampering our ability to develop preventions. Periventricular leukomalacia is a severe form of white matter injury. In the present study, we explored the effects of cerebral ischemia and/or intrauterine inflammation on the development of oligodendroglia in the cerebral white matter using chronically instrumented fetal sheep. Each fetus received one of three insults: hemorrhage, inflammation and their combination. In the hemorrhage group, 40% of the fetoplacental blood volume was acutely withdrawn, and 24 hours after removal, the blood was returned to the fetus. The inflammation group received intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin and thus suffered from necrotizing funisitis and chorioamnionitis. The inflammatory hemorrhage group underwent acute hemorrhage under the inflammatory state. The sham group received no insults. Importantly, periventricular leukomalacia was not detected in the sham and the inflammation groups. Differentiating oligodendroglia at various developmental stages were identified by immunohistochemical analysis with specific antibodies. No difference in the density of oligodendroglial progenitors was detected among the four groups, whereas oligodendroglial precursors were significantly reduced in the three insult groups, compared to sham control. Moreover, the density of immature oligodendroglia was higher in the inflammation group and the inflammatory hemorrhage group, while the density of mature oligodendroglia was highest in the hemorrhage group. We propose that cerebral ischemia or intrauterine inflammation induces the differentiation of oligodendroglial precursors in preterm fetuses, eventually resulting in their exhaustion.

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Effect of intrauterine inflammation on fetal cerebral hemodynamics and white-matter injury in chronically instrumented fetal sheep

Cited by 19 publications

References 25 publications

Novel modification of an artificial placenta: pumpless arteriovenous extracorporeal life support in a premature lamb model

Novel modification of an artificial placenta: pumpless arteriovenous extracorporeal life support in a premature lamb model

Respiratory support for premature neonates in the delivery room: effects on cardiovascular function and the development of brain injury

Cerebral Ischemia or Intrauterine Inflammation Promotes Differentiation of Oligodendroglial Precursors in Preterm Ovine Fetuses: Possible Cellular Basis for White Matter Injury

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