用于心室辅助装置血流动力学性能评价的体外模拟循环系统技术进展

体外模拟循环系统(mock circulatory systems,MCS)是一个模拟人体循环系统血流动力学状态的试验平台,被广泛用于心室辅助装置和人工瓣膜等心血管人工器官的体外性能评价和生机电系统中的血流动力学响应研究。通过调整模拟心脏的驱动元件和模拟血管系统的集中参数元件,MCS可以模拟人体健康、运动、心力衰竭等不同生理状态的血流动力学特性。自1960年代至今,MCS研发目标从满足最基本的心室辅助装置或机械瓣膜的系统性能评价要求,已发展到能够复现局部重要器官的血流动力学状态。总结MCS目前的设计原则、系统搭建以及研究进展和未来展望。     

完全磁悬浮心室辅助装置的体外模拟循环系统实验研究

目的研究我国自主研发的第3代完全磁悬浮心室辅助装置(CH-VAD)对于心衰患者的循环辅助效果。方法建立一套体外模拟循环系统(mock circulatory system,MCS)。该系统能够模拟人体健康休息状态以及心力衰竭状态,并与CH-VAD协同工作,测试CH-VAD在连续流状态下的辅助效果。另外,对CH-VAD的搏动流控制方法进行测试,该模式采用正弦波速度波形,使CH-VAD的运行与MCS心室周期同步。结果 CH-VAD在正常连续流状态下能够使心衰状态的血流动力学参数(动脉压、心排量)恢复到正常范围。初步的搏动流测试结果显示,当前的速度搏动幅值对血流动力学影响较小,搏动流状态下与连续流状态所对应的平均动脉压、动脉脉压、平均心排量与心排量波形等差异不大。结论 CH-VAD能够通过搏动控制器产生一定程度的速度搏动,提供足够的心室辅助,并可以进一步改良优化,提供符合生理条件的搏动血流。所研制的MCS能够提供心室辅助装置以及其他机械循环辅助装置一个有效、可控的体外测试平台,是机械循环辅助装置设计、优化和验证的重要工具。     

Circulatory assistance in small infants and neonates with a hydraulically driven system: a viable option?

We have developed a new drive system for a cardiac assist system for use with newborns and infants. This study reports results of animal experiments in which this system was tested using a commercially available 25-ml ventricle. A major property of the device is its hydraulic mode, which allows not only for the conventional full-empty mode (chamber completely filled in diastole) but also for the filled-empty mode, in which the chamber is completely emptied in systole but only partially filled in systole; this mode gives full flexibility to adjust the pump frequency for any given pump flow rate. The assist device was applied in eight pigs (weight 9-14 kg) for left ventricular assistance during normal and impaired cardiac function (pacing-induced cardiac shock, mean arterial blood pressure less than 40 mmHg). Both, full-empty and filled-empty mode during normal cardiac function led to significantly decreased pulmonary capillary wedge pressure, suggesting load reduction of the right ventricle. In impaired cardiac function, circulatory assistance increased the diminished cardiac output and systolic arterial blood pressure, although only the latter was statistically significant. Neither arterial lactate concentration nor oxygen uptake was reduced during circulatory assistance for normal and impaired cardiac function. These results suggest that the cardiac ventricular assist device can be used as an effective circulatory assist device and that the function of the newly introduced filled-empty mode, which allows for a high degree of functional flexibility, is not inferior to that of the classical, but less flexible, full-empty mode.     

Modelling in the study of interaction of Hemopump device and artificial ventilation

The aim of this work is to evaluate in different ventricular conditions the influence of joint mechanical ventilation (MV) and Hemopump assistance. To perform this study, we used a computer simulator of human cardiovascular system where the influence of MV was introduced changing thoracic pressure to positive values. The simulation confirmed that haemodynamic variables are highly sensitive to thoracic pressure changes. On the other hand, Hemopump assistance raises, among the others, mean aortic pressure, total cardiac output (left ventricular output flow plus Hemopump flow) and coronary flow. The simulation showed that the joint action of Hemopump and positive thoracic pressure diminishes these effects.     

Development of a Mathematical Model of the Human Circulatory System

A mathematical lumped parameter model of the human circulatory system (HCS) has been developed to complement in vitro testing of ventricular assist devices. Components included in this model represent the major parts of the systemic HCS loop, with all component parameters based on physiological data available in the literature. Two model configurations are presented in this paper, the first featuring elements with purely linear constitutive relations, and the second featuring nonlinear constitutive relations for the larger vessels. Three different aortic compliance functions are presented, and a pressure-dependent venous flow resistance is used to simulate venous collapse. The mathematical model produces reasonable systemic pressure and flow behaviour, and graphs of this data are included.     

Sarcomere-length dependence of lattice volume and radial mass transfer of myosin cross-bridges in rat papillary muscle

We examined the sarcomere length-dependence of the spacing of the hexagonal lattice of the myofilaments and the mass transfer of myosin cross-bridges during contraction of right ventricular papillary muscle of the rat. The lattice spacing and mass transfer were measured by using X-ray diffraction, and the sarcomere length was monitored by laser diffraction at the same time. Although the lattice spacing and the sarcomere length were inversely related, their relationship was not exactly isovolumic. The cell volume decreased by about 15% when the sarcomere length was shortened from 2.3 µm to 1.8 µm. Twitch tension increased with sarcomere length (the Frank–Starling law). At the peak tension, the ratio of the intensity of the (1,0) equatorial reflection to that of the (1,1) reflection was smaller when the tension was greater, showing that the larger tension at a longer sarcomere length accompanies a larger amount of mass transfer of cross-bridges from the thick to the thin filament. The result suggests that the Frank–Starling law is due to an increase in the number of myosin heads attached to actin, not in the average force produced by each head.     

Effect of the elastic conditions around a stentless valvular bioprosthesis on opening behavior

Stentless valvular bioprostheses have been used clinically for over 8 years and the excellent properties of the bioprostheses have been demonstrated in clinical studies. The present study examined how differing elastic conditions around the bioprosthesis at the aortic position affect the hydrodynamic characteristics of the bioprosthesis. Bioprosthesis implantation is typically performed using either the subcoronary or the full-root technique. These procedures for implanting a stentless prosthetic heart valve at the aortic root were hydrodynamically evaluated in a mock circulatory system. Forward flow rate was 11% greater with the subcoronary technique than with the full-root technique. In a high-speed video camera study, the orifice area at full opening was 12% larger for the subcoronary technique than for the full-root technique. Evaluation of bioprosthetic characteristics in terms of mechanical conditions is important when considering surgical options.     

High‐Efficiency Preparation of Macrocyclic Polymers via a Circulatory Extraction–Cyclization Strategy

Typically, intramolecular cyclization reactions need to be conducted at high dilution to avoid interchain coupling, which leads to the production of cyclic polymer at an extremely low output. Herein, a high‐efficiency Cu‐catalyzed azide/alkyne cycloaddition “click” synthesis of cyclic polystyrene (PS) and cyclic poly (methyl methacrylate) (PMMA) is reported via a circulatory technique of evaporation–condensation–extraction–inflow strategy by the utilization of elaborately designed equipment. High‐output cyclic PS (one batch, 0.71 g cyclic polymer from 1.0 g linear polymer loading) and cyclic PMMA (one batch, 0.62 g cyclic PMMA from 1.0 g linear polymer loading) are achieved. This promising preparation should be beneficial to the large‐scale application and research of cyclic polymers.

     

简易模拟心血管系统的设计与控制

为评测人工心脏,尤其是直接辅助式人工心脏,本文提出了利用泵、阀、管道、弹性腔和相应的控制器建立一套能反映血液动力学特性的简易体外血液循环模拟实验装置的方法。在该装置中,任意时刻流量的估计,是利用测量模拟心脏的血压和循环周期总流量获得。通过改变控制信号的频率、占空比和阀的开度模拟心脏不同心率、不同心收缩周期、不同程度的泵血功能,实验结果与生理情况分析基本相符合。该装置的模拟心脏具有类似心脏的形状,直接心辅装置可以直接固定在其上工作。     

A novel homozygous variant in REN in a family presenting with classic features of disorders involving the renin–angiotensin pathway,without renal tubular dysgenesis

Autosomal recessively inherited pathogenic variants in genes associated with the renin–angiotensin–aldosterone system (RAAS) result in early onset oligohydramnios and clinical features of the Potter sequence, typically in association with proximal renal tubules dysgenesis. We describe two siblings and a first cousin who had severe oligohydramnios in the second trimester, and presented at birth with loose skin, wide fontanelles and sutures, and pulmonary insufficiency. Two had refractory hypotension during their brief lives and one received palliative care after birth. All were found to have a homozygous nonsense variant, REN: c.891delG; p.Tyr287*, on exome sequencing. Autopsy limited to the genitourinary system in two of the children revealed normal renal tubular histology in both. Immunoblotting confirmed diminished expression of renin within cultured skin fibroblasts. To our knowledge, this is the first identification of an association between biallelic variants in REN and oligohydramnios in the absence of renal tubular dysgenesis. Due to its role in the RAAS, it has previously been proposed that the decreased expression of REN results in hypotension, ischemia, and decreased urine production. We suggest sequencing of genes in the RAAS, including REN, should be considered in cases of severe early onset oligohydramnios, even when renal morphology and histology are normal.