A Parallelized Pumpless Artificial Placenta System Significantly Prolonged Survival Time in a Preterm Lamb Model

Abstract

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.

An extra-uterine system to physiologically support the extreme premature lamb

“…Most attempts have been limited by subphysiologic circuit flows and rapid haemodynamic decompensation despite the use of vasopressor support and other measures24254446. Recently, Miura et al 45. reported survival of lamb fetuses on a pumpless parallelized circuit up to a predetermined limit of 60 h. In this report, the animals remained relatively haemodynamically stable.…”

“…A pumpless circuit powered by the fetal heart is not a new concept and has been the initial approach taken by many investigators232425444546. The advantages include simplicity, absence of pump-induced haemolysis and the potential for at least some autoregulation of circuit blood flow.…”

“…In addition, all other access sites require an operative procedure on the fetus for both insertion and removal of cannulas, require stabilization of cannulas to avoid catastrophic decannulation events and raise concern for compromise of blood flow to the brain or other structures, depending upon the vessel utilized. While many investigators have utilized the umbilical vessels, most have placed their cannulas into the central vasculature to avoid umbilical vascular spasm7811121314152324254546. This is possible in sheep or goats, but not possible and would likely be hazardous for arterial cannula placement in the human fetus due to the tortuous course of the umbilical arteries and the large cannulas required.…”

Stable Control of Physiological Parameters, But Not Infection, in Preterm Lambs Maintained on Ex Vivo Uterine Environment Therapy

“…All EVE components used in this study were arranged in an identical, parallelized orientation as those used in our previous study . In brief, the artificial placenta circuit consisted of parallelized membranous oxygenators and polyvinyl chloride tubes. The entire circuit was heparin‐coated.…”

The contribution of ovine models to perinatal respiratory physiology

“…Among other approaches, the concept of the artificial placenta was first tested some 50 years ago (194). Several groups of researchers from around the world have since developed an enhanced extrauterine artificial placenta, using extracorporeal membranous oxygenation via the umbilical vessels in very preterm lambs (195)(196)(197)(198)(199)(200). If successful, this method, alone or in combination with gentle ventilation approaches, could represent a major breakthrough for ventilator-induced lung injury and BPD prevention in extreme preterm infants.…”