Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta

Abstract

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit (n = 12; 98 ± 4 days; 743 ± 350 g). The umbilical vessels were cannulated, and fetuses were supported for 46.4 ± 46.8 h using the pumped AP versus 11 ± 13 h on the pumpless AP circuit. Upon initiation of AP support on the pumped system, we observed supraphysiologic circuit flows, tachycardia, and hypertension, while animals maintained on a pumpless AP circuit exhibited subphysiologic flows. On the pumped AP circuit, there was a progressive decline in umbilical vein (UV) flow and oxygen delivery. We conclude that the addition of a centrifugal pump to the AP circuit improves survival of preterm pigs by augmenting UV flow through the reduction of right ventricular afterload. However, we continued to observe the development of heart failure within a matter of days.

Advanced imaging of fetal cardiac function

“…For example, strain imaging has been shown to detect functional abnormalities in human fetuses with cardiac disease ( 111 ) and hypoxemic sheep ( 93 ). Figure 4 shows cardiac strain imaging in a preclinical pig model of the artificial placenta ( 131 , 132 ). In Figure 5 we applied strain analysis in the two human fetuses with CHD shown in Figure 2 and revealed changes in strain associated with reductions in combined ventricular output.…”

Transferring an extremely premature infant to an extra-uterine life support system: a prospective view on the obstetric procedure

“…Additional efforts could include protection from intense light while allowing visual examination by medical staff. For instance, Charest-Pekeski et al covered biobags to prevent light transmission to the fetus and mimic uterine conditions more accurately ( 7 ). While detailing these requirements is beyond the scope of this review, we believe that the obstetric procedure should be in line with the attenuation of triggers offered in an LFC and therefore avoid exposure to temperature shifts, noise, and harsh directed lights.…”

“…This involves maintaining the infant in a fetal physiological state [i.e., as a perinate (5)] with the lungs submerged in amniotic fluid and maintaining a fetal blood circuit through the umbilical vessels via an artificial placenta (AP). Progress on the development of a fluid environment, maintenance of fetal circulation, and physiological placental blood flow have all led to raised hopes that clinical application has come within reach (3,(6)(7)(8)(9)(10)(11)(12). Now that human trials are under consideration (12,13), the methods used in animal studies must be translated to suit human patients.…”

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

“…Key physiological parameters and blood lactate levels mostly remained within their reference ranges or rapidly returned to reference range ( Faber and Green, 1972 ; Parisi and Walsh, 1989 ; Assad et al, 2001 ) after APT was started unless bleeding and/or constriction of umbilical arteries occurred ( Figure 1 ; Table 2 ). Given previous studies in which incompatibility of the extracorporeal system likely caused progressive circulatory failure in extremely preterm mammals less than 1,000 g, resulting in fetal death ( Hornick et al, 2019 ; Charest-Pekeski et al, 2021 ; Charest-Pekeski et al, 2022 ), our APT platform allowed for more stable physiological maintenance, constant fetal (albeit high) urine output and reassuring fetal movement ( Tables 2 – 6 ). In addition, biochemical tests did not indicate injury of key organs including the liver and kidney ( Table 3 ).…”

“…Despite these important achievements, most studies have employed fetal sheep or goats significantly larger and more mature than EPIs, the likely clinical candidates for APT. Recently, Charest-Pekeski et al used late preterm fetal pigs with a pumpless APT system (98 d/115d-term: 743 ± 350 g: 11 ± 13 h survival) and a pump-driven APT system (102 d: 616 ± 139 g: 46.4 ± 46.8 h survival); they reported fetal death due to progressive decline in the umbilical vein (UV) flow and oxygen delivery ( Charest-Pekeski et al, 2021 ; Charest-Pekeski et al, 2022 ). Hornick et al also demonstrated the feasibility of catheterizing the extremely preterm lamb umbilical cord, and maintained fetuses on a pumpless APT system driven by fetal cardiac heart (85-96d/145 d-term: 641 ± 71 g: 140 ± 7 h survival); their report highlighted key challenges in relation to fetal death with progressive hydrops on and after around 72 h, presumably due to cardiac failure ( Hornick et al, 2019 ).…”