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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Ex vivo uterine environment (EVE) therapy is an experimental neonatal intensive care strategy wherein gas exchange is performed by membranous oxygenators attached to the umbilical vessels. Our aim was to assess the ability of a newly refined EVE system to maintain key physiological parameters in preterm lambs within optimal ranges for 48 h. EVE group; n = 6: Preterm lambs were delivered under general anesthesia at 115 ± 2 days of gestational age. Animals were submerged in a bath of artificial amniotic fluid on EVE therapy for 48 h. Physiological parameters were monitored in real-time over the length of the experiment. Control group; n = 11: Ewes carrying a single fetus (115 ± 2 days of gestational age) underwent recovery surgery to allow placement of a fetal carotid artery catheter. Fetuses received an infusion of sterile saline only. After euthanasia, EVE and Control group fetuses underwent necroscopy to perform static pressure-volume curves and for sampling of lung and cord blood plasma for molecular analyses. Five out of six fetuses in the EVE group completed the study period with key physiological variables remaining within their respective reference ranges for the duration of the 48 h study. Bacteremia was identified in four out of five EVE fetuses, and was associated with a systemic inflammatory response. Using our refined EVE therapy platform, preterm lambs were maintained in a stable physiological condition for 48 h. These findings represent a significant advance over earlier work with this system; however, the identification of bacteremia and a fetal inflammatory response suggests that further refinement to the EVE therapy platform is required.

An artificial placenta (AP) is an arterio-venous extracorporeal life support system that is connected to the fetal circulation via the umbilical vasculature. Previously, we published an article describing a pumpless AP system with a small priming volume. We subsequently developed a parallelized system, hypothesizing that the reduced circuit resistance conveyed by this modification would enable healthy fetal survival time to be prolonged. We conducted experiments using a premature lamb model to test this hypothesis. As a result, the fetal survival period was significantly prolonged (60.4 ± 3.8 vs. 18.2 ± 3.2 h, P < 0.01), and circuit resistance and minimal blood lactate levels were significantly lower in the parallel circuit group, compared with our previous single circuit group. Fetal physiological parameters remained stable until the conclusion of the experiments. In summary, parallelization of the AP system was associated with reduced circuit resistance and lactate levels and allowed preterm lamb fetuses to survive for a significantly longer period when compared with previous studies.

The mechanical ventilation following severe prenatal inflammation did not lead to overt lung injury or degradation of elastin but resulted in arrested alveolarization in the lungs of preterm lambs.