Assessment of synthetic red cell therapy for extremely preterm ovine fetuses maintained on an artificial placenta life‐support platform

Usuda, Haruo; Saito, Masatoshi; Ikeda, Hideyuki; Sato, Shinichi; Kumagai, Yusaku; Saito, Yuya; Kawamura, Shinichi; Hanita, Takushi; Sakai, Hiromi; Kure, Shigeo; Yaegashi, Nobuo; Newnham, John P.; Kemp, Matthew W.; Watanabe, Shimpei

doi:10.1111/aor.14155

Cited by 2 publications

(3 citation statements)

References 46 publications

(166 reference statements)

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“…A circuit flow of less than 150 ml/min (regardless of cause) resulted in the intravenous administration of higher-dose nitroglycerin (2–10 μg/kg/min, Millisrol Inj. Nippon Kayaku Co., Ltd., Tokyo, Japan) so as to prevent constriction of umbilical vessels and maintain circuit blood flow ( Usuda et al, 2022b ).…”

Section: Methodsmentioning

confidence: 99%

Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth

Usuda,

Ikeda,

Watanabe

et al. 2023

Front. Physiol.

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Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system.Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive time-course blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA.Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected.Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, but growth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology.

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Section: Methodsmentioning

confidence: 99%

Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth

Usuda,

Ikeda,

Watanabe

et al. 2023

Front. Physiol.

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“…42 It can also help to establish an artificial placenta life support platform (APT) to supply oxygen to extremely premature infants. 43 1.4.3. Polydopamine-Encapsulated Hb.…”

Section: Hb-based Oxygen Carriersmentioning

confidence: 99%

“…HbV-based oxygen carriers can also be used as organ supports, stabilizing the circulation of pneumonectomy rats with hemorrhagic shock . It can also help to establish an artificial placenta life support platform (APT) to supply oxygen to extremely premature infants …”

Section: Hb-based Oxygen Carriersmentioning

confidence: 99%

Research Progress in Oxygen Carrier Design and Application

Ye,

Zheng,

Chen

et al. 2023

Mol. Pharmaceutics

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Ischemia or hypoxia can lead to pathological changes in the metabolism and function of tissues and then lead to various diseases. Timely and effective blood resuscitation or improvement of hypoxia is very important for the treatment of diseases. However, there is a need to develop stable, nontoxic, and immunologically inert oxygen carriers due to limitations such as blood shortages, different blood types, and the risk of transmitting infections. With the development of various technologies, oxygen carriers based on hemoglobin and perfluorocarbon have been widely studied in recent years. This paper reviews the development and application of hemoglobin and perfluorocarbon oxygen carriers. The design of oxygen carriers was analyzed, and their application as blood substitutes or oxygen carriers in various hypoxic diseases was discussed. Finally, the characteristics and future research of ideal oxygen carriers were prospected to provide reference for follow-up research.

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Assessment of synthetic red cell therapy for extremely preterm ovine fetuses maintained on an artificial placenta life‐support platform

Cited by 2 publications

References 46 publications

Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth

Artificial placenta support of extremely preterm ovine fetuses at the border of viability for up to 336 hours with maintenance of systemic circulation but reduced somatic and organ growth

Research Progress in Oxygen Carrier Design and Application

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