Artificial Placenta: Long‐Term Extrauterine Incubation of Isolated Goat Fetuses

Abstract

Previously, this group reported on a system of extrauterine incubation of a goat fetus, in which the fetus is surrounded by artificial amniotic fluid and connected to the circuit with an ECMO (extracorporeal membrane oxygenator) by the umbilical arteries and veins. The following is a summary of recent progress using an improved method of catheterization and a new system that included a dialyzer within the circuit. Nine goat fetuses were used in this experiment. Six goats were successfully incubated; the duration of their incubation was 146.5 2 61.3 h (mean * SD). The longest one was 236 h. Slowly progressive circulatory depression was thought to be the main cause of fetal death. Marked tendencies to bleeding and water retention were not observed in any cases. Stable serum electrolyte levels were maintained.

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

“…However, external flow regulators were required to reduce blood flow through the circuit to reverse lactic acidosis, and evidence of white matter brain injury was observed on histology. Most investigators have added pumps to arteriovenous systems to address the limitation of subphysiologic flow in pumpless systems7891112131415. While most attempts have been short-lived culminating in circulatory failure, prolonged survival of up to 543 h was achieved in two fetal goats12.…”

“…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.…”

“…However, the development of an ‘artificial placenta' has been the subject of investigation for over 50 years67, with only limited success. The primary obstacles have been progressive circulatory failure due to preload or afterload imbalance imposed on the fetal heart by oxygenator resistance and pump-supported circuits, the use of open fluid incubators resulting in contamination and fetal sepsis and problems related to umbilical vascular access resulting in vascular spasm6789101112131415. To address these obstacles we have designed a system consisting of three main components, specifically, a pumpless arteriovenous circuit, a closed fluid environment with continuous fluid exchange and a new technique of umbilical vascular access.…”

Development of an artificial placenta I: pumpless arterio-venous extracorporeal life support in a neonatal sheep model

“…Dr. Unno's group [15] reported several long-term successes, with incubation times ranging from 165 to 543 hours using a pump-driven AV-ECLS circuit [16,17]. Improvements included tighter control of the oxygenator sweep gas, total parenteral nutrition, use of a reservoir, addition of a dialyzer, and the use of muscle relaxants.…”

A paradigm shift in the treatment of extreme prematurity

“…[34] Further modifications of the incubation system lead to improved survival in subsequent studies with a mean of 146hrs and as long as 236h. [35] Unno and colleagues made further modifications using AV-ECLS with the implementation of a sedative (diazepam) and muscle relaxant (pancuronium) achieving survival in two sheep of 494 and 534 hrsfollowed by successful transition to a ventilator for 1 week. [36] This group went on to demonstrate that ongoing fetal lung growth and maturation was possible with AP support.…”