DEVELOPMENT OF AN ARTIFICIAL PLACENTA

人工胎盘的开发

• 批准号: 06557066
• 负责人: KUWABARA Yoshinori
• 金额: $ 9.73万
• 依托单位: JUNTENDO UNIVERSITY,SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06557066/
• 关键词: artificial placenta; extrauterine fetal incubation; experimental perinatology; extracorporeal circulation; extracorporeal membrane oxygenator; 対外循環

The aim of our study was to newly develop an extrauterine incubation system closely resembled that of a fetus in utero in both the extracorporeal and intracorporeal environments, in order to incubate and extremely premature baby or a fetus having a disease which should be treated in utero. The extrauterine incubation system consisted of an artificial womb containing artificial amniotic fluid and a cpmplete artificial placental system with a membrane oxygenator which was used for A-V ECMO.Materials we used were goat fetuses. After long-term extrauterine incubation, goat fetuses were tried to remove from the incubator and stimulated to initiate lung respiration. At the first, we examined the feasibility of long-term extrauterine incubation of relatively matured (125-130 days of gestation) goat fetuses, and at the second, premature (90-100 days of gestation) goat fetuses. In premature goat fetuses as well as relatively matured ones, long-term extrauterine incubation without cardiac failure could be achieved by administration of diazepam and pancronium bromide into the blood circuit to supress fetal movement an swallowing. Because they could be implicated in fetal deterioration during extrauterine fetal incubation. After removal from the incubator, these animals could survive for more than 1 week, if only with ventilator support. In consequence, we could prove that long-term umbilical A-V ECMO was in itself not harmful to fetal survival. But the administered pancronium bromide might have caused fetal neuromuscular disturbances that could prevent spontaneous breathing. Before this system can be applied for humans, numerous problems such as water homeostasis and nutrition maintenance as well as the muscle weakness due to long term immobilization must be resolved.

我们研究的目的是新开发一种在体外和子宫内环境中与子宫内胎儿非常相似的子宫外孵育系统，以便孵育极早产儿或患有应在子宫内治疗的疾病的胎儿。体外培养系统由一个装有人工羊水的人工子宫和一个完整的人工胎盘系统组成，人工胎盘系统带有用于A-V ECMO的膜式氧合器。在长期子宫外孵育后，尝试将山羊胎儿从孵育器中取出并刺激以启动肺呼吸。首先，我们研究了相对成熟（妊娠125-130天）的山羊胎儿长期宫外孵育的可行性，第二，早产（妊娠90-100天）的山羊胎儿。在早产和相对成熟的山羊胎儿中，通过将地西泮和潘可溴铵施用到血液回路中以抑制胎动和吞咽，可以实现长期的宫外孵育而不发生心力衰竭。因为它们可能与子宫外胎儿孵化期间的胎儿恶化有关。从培养箱中取出后，这些动物可以存活超过1周，如果只有呼吸机支持的话。因此，我们可以证明长期脐动静脉ECMO本身对胎儿存活没有危害。但服用潘可溴铵可能会导致胎儿神经肌肉紊乱，从而阻止自主呼吸。在该系统应用于人类之前，必须解决许多问题，例如水平衡和营养维持以及由于长期固定而导致的肌肉无力。

项目成果

Shigeru Itoh, Koyo Yoshida, Yasushi Nakamura, Naoki Mitsuhashi, Yoshinori Kuwabara: "Cardiovascular Responses of Goat Fetuses to Hypercapnia during Extrauterine Incubation Using Extracorporeal Membrane Oxygenation." J.Obstet.Gynecol.Res.(in press).

Shigeru Itoh、Koyo Yoshida、Yasushi Nakamura、Naoki Mitsuhashi、Yoshinori Kuwabara：“使用体外膜氧合进行宫外孵化期间山羊胎儿对高碳酸血症的心血管反应。”

Kuwabara Yoshinori, Koyo Yoshida, Yasushi Nakamura, Shigeru Itoh: "Extrauterine Incubation of Isolated Goat Fetuses by Using Artificial Placenta." J.Repro.Develop.41 (5). j55-j60 (1995)

Kuwabara Yoshinori、Koyo Yoshida、Yasushi Nakamura、Shigeru Itoh：“使用人工胎盘对离体山羊胎儿进行宫外孵化”。

Nobuya Unnno, Yoshinori Kuwabara, et al: "Development of an Artificial Olacenta : Endocrine Responses of Goat Fetuses during Long-Term Extrauterine Incubation with Umbilical Arteriovenous Extracorporeal Membrane Oxygenation." Endocrine Journal. 41 (Suppl)

Nobuya Unnno、Yoshinori Kuwabara 等人：“人工 Olacenta 的开发：通过脐动静脉体外膜氧合长期宫外孵化期间山羊胎儿的内分泌反应。”