In vitro perfusion of hybrid artificial pancreas devices at low flow rates.
In vitro perfusion of hybrid artificial pancreas devices at low flow rates.
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低流速混合人工胰腺装置的体外灌注。
DOI：
10.1097/00002480-199207000-00073
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Stephens,CL
中科院分区：
文献类型：
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作者：
Ramírez,CA;López,M;Stephens,CL
I型糖尿病的特征在于由于缺乏功能性β细胞而导致的胰岛素不足。为了取代注射疗法，开发了混合人工胰腺（HAP）等方案。它由一个丙烯酸外壳组成，外壳内包有一个半渗透性中空纤维膜。供体胰岛可以通过壳体中的端口接种在环形空间中，并且因此与受体的血流或灌注液分离。在将HAP缩放到人类大小之前，必须更好地理解其胰岛素对灌注葡萄糖挑战的响应动力学。在这项研究中，HAP的胰岛素反应后，一个步骤增加的内腔葡萄糖浓度被确定为一个函数的径向厚度的环形空间（0.173-0.973毫米）和胰岛分布在1毫升/分钟的流速。装置包含一个单一的，65毫米长的纤维被使用。使用标准胶原酶消化技术分离大鼠胰岛。在非接种HAP灌注中，葡萄糖和胰岛素从瓣环间隙的洗脱时间取决于流速和径向厚度。当以10 ml/min灌注时，两种溶质在< 3 min内从最小的装置中去除。因此，HAP内的溶质转运非常快。在接种的HAP灌注中，使装置经受腔内葡萄糖浓度的逐步增加。收集HAP流出物的连续样品并测定葡萄糖和胰岛素。胰岛在环形空间中的空间分布是决定HAP胰岛素反应的最重要因素之一。因此，在出口处接种的装置具有立即或快速（< 5分钟）响应，而在入口处或中心接种的HAP中观察到高达85分钟的滞后时间。这项研究提供了第一个实验证据，一个可接受的HAP设计为人类是可能的，通过最大限度地减少环形空间的体积，并通过接种在出口的胰岛。
Type I diabetes is characterized by insulin insufficiency due to lack of functional beta cells. To replace injection therapy, schemes such as the Hybrid Artificial Pancreas (HAP) were developed. This consists of an acrylic housing enclosing a semipermeable hollow fiber membrane. Donor islets can be seeded in the annular space through a port in the housing, and thus are separated from the recipient's bloodstream or perfusate. Before scaling the HAP to human size, the dynamics of its insulin response to a perfusion glucose challenge must be better understood. In this study, the HAP's insulin response after a step increase in the lumenal glucose concentration was determined as a function of the radial thickness of the annular space (0.173–0.973 mm) and islet distribution at a flow rate of 1 ml/min. Devices containing a single, 65 mm long fiber were used. Rat islets were isolated using standard collagenase digestion techniques. In unseeded HAP perfusions, the washout time for glucose and insulin from the annular space was dependent on flow rate and radial thickness. Both solutes were removed in< 3 min from the smallest devices when perfused at 10 ml/min. Thus, solute transport within the HAP is very fast. In the seeded HAP perfusions, the devices were subjected to a step increase in the lumenal glucose concentration. Sequential samples of the HAP effluent were collected and assayed for glucose and insulin. The spatial distribution of the islets in the annular space was one of the most important factors in determining the HAP's insulin response. Thus, devices seeded at the outlet had an immediate or fast (< 5 min) response, whereas lag times of up to 85 min were observed in HAPs seeded at the inlet or centrally. This study provides the first experimental evidence that an acceptable HAP design for humans is possible by minimizing the annular space volume and by seeding the islets at the outlet.