Two-Dimensional Simulation of Red Blood Cell Deformation and Lateral Migration in Microvessels

A theoretical method is used to simulate the motion and deformation of mammalian red blood cells (RBCs) in microvessels, based on knowledge of the mechanical characteristics of RBCs. Each RBC is represented as a set of interconnected viscoelastic elements in two dimensions. The motion and deformation of the cell and the motion of the surrounding fluid are computed using a finite-element numerical method. Simulations of RBC motion in simple shear flow of a high-viscosity fluid show “tank-treading’’ motion of the membrane around the cell perimeter, as observed experimentally. With appropriate choice of the parameters representing RBC mechanical properties, the tank-treading frequency and cell elongation agree closely with observations over a range of shear rates. In simulations of RBC motion in capillary-sized channels, initially circular cell shapes rapidly approach shapes typical of those seen experimentally in capillaries, convex in front and concave at the rear. An isolated RBC entering an 8-μm capillary close to the wall is predicted to migrate in the lateral direction as it traverses the capillary, achieving a position near the center-line after traveling a distance of about 60 μm. Cell trajectories agree closely with those observed in microvessels of the rat mesentery.     

玻璃化保存工程化组织产品的实验与技术

目的:总结近年来玻璃化保存技术的新进展和多种工程化组织玻璃化保存的实验研究。探讨影响工程化组织低温保存的主要因素、评价指标等,以期指导玻璃化保存工程化组织的实验研究。资料来源:应用计算机检索Medline,EBSCO,ScienceDirect Onsite以及google scholar引擎中1980-02/2006-05关于细胞和组织低温保存的文献,检索词“tissue engineering,engineered tissue,cryopreservation,vitrification,ice-free cryopreservation,vitreous cryopreservation”,检索词被分别组合进行检索,限定文献语言种类为English。同时计算机检索万方数据库1980-02/2006-05关于细胞和组织低温保存的文献,检索词“组织工程,工程化组织,冻存,玻璃化保存”,限定文献语言种类为中文。资料选择:对资料进行初审,选出与研究关系密切的文献。纳入标准:研究对象为动物或人,包括基础与临床研究内容。重点选取与玻璃化保存技术基本原理相关以及具体的工程化构建物玻璃化保存相关的文献。排除标准:关于配子,胚胎和植物,食品等的玻璃化保存文章。资料提炼:共检索到122篇关于细胞和组织低温保存的文献,其中与本实验关系密切的文献17篇,间接相关的文献42篇,最终纳入31篇符合标准的文献。资料综合:组织工程产业化要求长期而稳定的保存包含活细胞的工程化组织产品,以及产品中细胞与材料的黏附。相对于传统的低温冻存技术而言,玻璃化保存因在保存过程中无细胞内外冰晶形成,可以改善复温后的细胞活力,并能保护细胞和支架材料之间的黏附。本文从近年来玻璃化保存技术的新进展和多种工程化组织玻璃化保存的实验研究进行综述,分析了玻璃化保存液要求高浓度,对细胞有非特异毒性损伤,对悬浮单细胞的玻璃化保存能得到较高的细胞存活,而与支架材料结合的种子细胞存活除受到冻存试剂和流程的影响外还受到自身结构的影响。结论:玻璃化保存是较好的生物系统保存方法,可以为工程化组织产品提供可靠的保存,但急需发现新的低毒高效的玻璃化试剂以及优化保存流程。     

Factors predicting the use of therapeutic hypothermia and survival in unconscious out-of-hospital cardiac arrest patients admitted to the ICU

Introduction

Therapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopted early in Norway. Since 2004 the general recommendation has been to cool all unconscious OHCA patients treated in the intensive care unit (ICU), but the decision to cool individual patients was left to the responsible physician. We assessed factors that were associated with use of TH and predicted survival.

Method

We conducted a retrospective observational study of prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at three university hospitals.

Results

A total of 715 unconscious patients older than 18 years of age, who suffered OHCA of both cardiac and non-cardiac causes, were included. With an overall TH use of 70%, the survival to discharge was 42%, with 90% of the survivors having a favourable cerebral outcome. Known positive prognostic factors such as witnessed arrest, bystander cardio pulmonary resuscitation (CPR), shockable rhythm and cardiac origin were all positive predictors of TH use and survival. On the other side, increasing age predicted a lower utilisation of TH: Odds Ratio (OR), 0.96 (95% CI, 0.94 to 0.97); as well as a lower survival: OR 0.96 (95% CI, 0.94 to 0.97). Female gender was also associated with a lower use of TH: OR 0.65 (95% CI, 0.43 to 0.97); and a poorer survival: OR 0.57 (95% CI, 0.36 to 0.92). After correcting for other prognostic factors, use of TH remained an independent predictor of improved survival with OR 1.91 (95% CI 1.18-3.06; P <0.001). Analysing subgroups divided after initial rhythm, these effects remained unchanged for patients with shockable rhythm, but not for patients with non-shockable rhythm where use of TH and female gender lost their predictive value.

Conclusions

Although TH was used in the majority of unconscious OHCA patients admitted to the ICU, actual use varied significantly between subgroups. Increasing age predicted both a decreased utilisation of TH as well as lower survival. Further, in patients with a shockable rhythm female gender predicted both a lower use of TH and poorer survival. Our results indicate an underutilisation of TH in some subgroups. Hence, more research on factors affecting TH use and the associated outcomes in subgroups of post-resuscitation patients is needed.     

International comparative field study of N8 evaluating factor VIII assay performance

Summary. Discrepancies between the one‐stage clotting assay and the chromogenic method, and also among different variations of each method, have been a significant challenge for one B‐domain deleted FVIII product. N8 is a B‐domain truncated FVIII product developed by Novo Nordisk. The comparison of N8 and Advate^® was performed in an international, multicentre, randomized and blinded field study of simulated postinfusion samples. Overall, Advate^® and N8 performed similarly in the one‐stage assay. In the one‐stage clotting assay, the measured mean FVIII levels of Advate^® vs. N8 were 0.046/0.047, 0.24/0.24, 0.58/0.60 and 0.82/0.83 IU mL^?1 for the target values of 0.03, 0.2, 0.6 and 0.9 IU mL^?1, respectively. In the chromogenic assays, the concentration estimates showed a tendency towards higher N8 values as compared with Advate^®; the measured FVIII levels of Advate^® vs. N8 were 0.030/0.032, 0.22/0.24, 0.65/0.74 and 0.98/1.08 IU mL^?1 for the target values of 0.03, 0.2, 0.6 and 0.9 IU mL^?1, respectively. In the one‐stage assays, the measured values were above 150% of target at the lowest concentration, decreasing to around 90% of target at the highest concentration. In contrast, the chromogenic assays were close to target at the lowest concentration and consistently above target at the three highest concentrations. Therefore, the ratio of chromogenic/one‐stage potencies was concentration dependent, ranging from 0.66 to 1.30. The SSC plasma standard was similar in both. Assay variability was similar for both compounds. The results show that N8 can be reliably measured in plasma without the need for a separate N8 standard.     

Mechanics and computational simulation of blood flow in microvessels

Blood is a concentrated suspension of red blood cells (RBCs). Motion and deformation of RBCs can be analyzed based on knowledge of their mechanical characteristics. Axisymmetric models for single-file motion of RBCs in capillaries yield predictions of apparent viscosity in good agreement with experimental results for diameters up to about 8 μm. Two-dimensional simulations, in which each RBC is represented as a set of interconnected viscoelastic elements, predict that off-centre RBCs in an 8-μm channel take asymmetric shapes and drift toward the centre-line. Predicted trajectories agree with observations in microvessels of the rat mesentery. An isolated RBC initially positioned near the wall of a 20-μm channel is deformed into an asymmetric shape, migrates away from the wall, and then enters a complex tumbling motion with continuous shape change. Realistic simulation of multiple interacting RBCs in microvessels remains as a major challenge.