Elevated plasma homocysteine levels are considered as a risk factor for cardiovascular diseases as well as preeclampsia—a pregnancy disorder characterized by hypertension and proteinuria. We previously generated mice lacking cystathionine γ-lyase (Cth) as cystathioninuria models and found them to be with cystathioninemia/homocysteinemia. We investigated whether Cth-deficient (Cth−/−) pregnant mice display any features of preeclampsia. Cth−/− females developed normally but showed mild hypertension (~10 mmHg systolic blood pressure elevation) in late pregnancy and mild proteinuria throughout development/pregnancy. Cth−/− dams had normal numbers of pups and exhibited normal maternal behavior except slightly lower breastfeeding activity. However, half of them could not raise their pups owing to defective lactation; they could produce/store the first milk in their mammary glands but not often provide milk to their pups after the first ejection. The serum oxytocin levels and oxytocin receptor expression in the mammary glands were comparable between wild-type and Cth−/− dams, but the contraction responses of mammary gland myoepithelial cells to oxytocin were significantly lower in Cth−/− dams. The contraction responses to oxytocin were lower in uteruses isolated from Cth−/− mice. Our results suggest that elevated homocysteine or other unknown factors in preeclampsia-like Cth−/− dams interfere with oxytocin that regulates milk ejection reflex.

Introduction We performed in vitro experiments using whole human blood without anticoagulants to clarify the activity of anticoagulant proteins on membranes coated with acrylate-copolymer (ACP) with a hydrophilic blood-contacting layer compared to those coated by immobilizing heparin (IHP) in extracorporeal circulation. Methods Whole human blood from healthy volunteers was recirculated in two types of experimental circuits with an ACP-coated reservoir and tubes and an ACP-coated or IHP-coated membrane. To compare the fluctuation of anticoagulant proteins, the circuit pressure at the inlet and outlet of the membrane was measured every 5 min; antithrombin antigen (ATQ), antithrombin activity, protein-C quantitation (PCQ), protein-C activity, protein-S free antigen (PSQ), and protein-S activity were measured at 0, 30, 60, 120, and 180 min in each experiment ( n = 5). Results The time taken to achieve high circuit pressure (> 300 mmHg) at the inlet of the membrane was significantly shorter in the ACP-coated membrane circuit (28 ± 2.7 min) than in the IHP-coated membrane circuit (54 ± 24 min); however, the ATQ, PCQ, and PSQ at 180 min of recirculation were significantly higher in the former than in the latter (all p < .05). Conclusions ACP-coated membranes can prevent the consumption of anticoagulant proteins but cannot delay circuit thrombogenicity compared to IHP-coated membranes. Considering patient care during the post-extracorporeal circulation period, the use of ACP coating, which can preserve anticoagulant protein, is better in extracorporeal circulation circuits.

Introduction The membrane oxygenator in extracorporeal circulation circuits is coated with acrylate-copolymer (ACP) or immobilized heparin (IHP) to enhance hemocompatibility. To evaluate the relative features of both coatings, we compared blood components circulated in the circuits with ACP-and IHP-coated membranes in vitro using whole human blood. Methods Whole human blood was heparinized and circulated in two experimental circuits with an ACP-coated reservoir, tubes, and an ACP- or IHP-coated membrane. Platelet (PLT) counts and the amount of total protein (TP), complement component 3 (C3), and complement component 4 (C4) were measured at 0, 8, 16, 24, and 32 h in each experiment ( n = 5). Results The PLT count at 0-h circulation was lower in the IHP-coated than in the ACP-coated circuits ( p = 0.034); however, no significant difference was observed at other time points. Reduction in TP at 8-h and 16-h circulation and in C3 at 32-h circulation was lesser in the ACP-coated than in the IHP-coated circuits ( p = 0.004, 0.034, and 0.027, respectively); reduction in TP and C3 at other time points and C4 at each time point was not significantly different. There were significant interactions between coating type and circulation duration in the PLT, TP, and C3 transitions ( p = 0.008, 0.020, and 0.043, respectively). Conclusions Our findings suggest that ACP-coated membranes can prevent the initial drop in PLT count and C3 consumption over 32 h, whereas IHP-coated membranes could not prevent this drop in extracorporeal circulation. Therefore, ACP-coated membranes are suitable for short- and long-term extracorporeal life support.