Studies on the ultrastructure of blood cells and the microaggregate fraction in stored human blood

Electron microscopy of citrate-phosphatedextrose (CPD) buffered bank blood performed over 21 days shows that the normal architecture of erythrocytes, platelets and leucocytes disappears and that deformed organelles, leucocyte ghosts, cell fragments and microaggregates accumulate. Leucocytes and platelets emerge as the most sensitive indicators of blood deterioration showing profound morphological changes from the first day. Microaggregates which passed through a 20-m high capacity transfusion filter were identified as platelet conglomerates, leucocyte ghost and platelet-leucocyte ghost coaggregates with diameters of 6–20, 20–30 and 30–40 m respectively. of these aggregates present in the filtrate, 62% fell into the size range of 20–40 m. The composition of microaggregates varies with storage time, the platelet conglomerates appear first during or after Day 1, leucocyte ghosts after Day 5 followed by platelet-leucocyte ghost coaggregate formation. At this stage the number of intact leucocytes and platelets is reduced and the filtrate shows an abundance of leucocyte debris. Microfiltration would thus appear to reduce but not eliminate the danger of microembolism and damage to capillary endothelium.     

Gaseous microemboli sizing in extracorporeal circuits using ultrasound backscatter

This paper describes efforts to estimate the size of gaseous microemboli (GME) in extracorporeal blood circuits based on the amplitude of backscattered ultrasound, starting with analytic modeling of the scattering behavior of GME in blood. After neglecting resonance effects, this model predicts a linear relationship between the amplitude of backscattered echoes and the diameter of GME. Computer simulations based on the cylindrical acoustic finite integration technique were performed to test some of the simplifying assumptions of the analytical model, with the simulations predicting small deviations from the linear approximation that could be treated as random scatter. Ultrasonic and microscopic measurements of injected GME were then performed on a test circuit to determine the linear correlation coefficient between echo amplitude and GME diameter in conditions like those employed in real cardiopulmonary bypass (CPB) circuits. The correlation coefficient determined through this study was further validated in a closed-loop CPB circuit using canine blood. This study shows that the amplitude of ultrasonic backscattered echoes can be used to accurately estimate the size distribution of a population of detected GME when the spacing of emboli is great enough to minimize interference and other multi-path scattering effects. With the high flow rates found in CPB circuits, typically ranging from 2 to 6 L per minute (equivalent to a flow velocity of 0.3 to 1 m/s through the circuit tubing), this assumption will be valid even when hundreds of emboli per second pass through the circuit. Therefore, sizing of GME using the ultrasonic backscatter models described in this paper is a viable method for estimating embolic load delivered to a patient during a CPB procedure.     

Newtonian viscous effects in ultrasonic emboli removal from blood

We have modeled the removal of emboli from cardiopulmonary bypass circuits via acoustic radiation force. Unless removed, emboli can result in cognitive deficit for those undergoing heart surgery with the use of extracorporeal circuits. There are a variety of mathematical formulations in the literature describing acoustic radiation force, but a lingering question that remains is how important viscosity of the blood and/or embolus is to the process. We implemented both inviscid and viscous models for acoustic radiation force on a sphere immersed in a fluid. We found that for this specific application, the inviscid model seems to be sufficient for predicting acoustic force upon emboli when compared with the chosen viscous model. Thus, the much simpler inviscid model could be used to optimize experimental techniques for ultrasonic emboli removal.     

微栓子监测在缺血性脑血管病中的临床应用与研究现状

目前缺血性脑血管病的微栓子发病机制已得到广泛研究,而利用经颅多普勒超声行微栓子监测也得到了一定的临床及科研支持。现从微栓子监测的应用基础、诊断标准及条件、微栓子与脑梗死亚型的相关性、临床药物的疗效评价、脑缺血事件复发的预测等方面对微栓子监测在缺血性脑血管病患者的临床应用与研究现状进行简要总结。     

Thoughts and Progress

The constant-pressure filtration (CPF) method has been developed to assess blood microemboli (BME) in terms of their ability to occlude microvascular flow. Previous reports suggest that the method is sensitive to the effects of platelet stimulation and to blood-pumping conditions. BME production and heparin activity were studied in bovine and human blood pumped by a Pellethane ventricle with Pellethane molded valves connected via smooth quick-connects to a Pellethane horseshoe-shaped reservoir. In each experiment, blood was collected into heparin by cardiac puncture from a stunned animal or by venepuncture from a human donor. The blood from each donor was filled into three ventricle-reservoir systems (50 cc ventricle and 1,500 cc reservoir for the bovine blood, and 20 cc ventricle and 150 cc reservoir for the human blood). One of the systems received aspirin (ASA; 25 mg/dl) shortly after the onset of pumping, whereas the other two served as pumping and non-pumping controls. The blood was pumped in a full-fill/full-eject mode for up to 10 h. BME concentration was measured by the CPF method in which the blood was filtered through 20-microns pore filters at 20 mm Hg for 10 s, and the flowrate curves were evaluated from occlusion model. Heparin activity was measured by the activated partial thromboplastin time (APTT) test. In the early period after the onset of pumping, the BME concentration increased, whereas the APTT decreased from an initial value of greater than 250 s, with the relative rate of change for both the BME and the APTT being the following: pumping control greater than pumping ASA blood greater than quiescent control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of index modulation in microembolic Doppler signals part I: radiation force as a new hypothesis-simulations

The purpose of this study was to reveal the cause of frequency modulation (FM) present in microembolic Doppler ultrasound signals. This novel explanation should help the development of sensitive microembolus discrimination techniques. We suggest that the frequency modulation detected is caused by the ultrasonic radiation force (URF) acting directly on microemboli. The frequency modulation and the imposed displacement were calculated using a numerical dynamic model. By setting simulation parameters with practical values, it was possible to reproduce most microembolic frequency modulation signatures. The most interesting findings in this study were that: (1) the ultrasound radiation force acting on a gaseous microembolus and its corresponding cumulative displacement were far higher than those obtained for a solid microembolus, and that is encouraging for discrimination purposes; and 2) the calculated frequency modulation indices (FMIs) (≈20 kHz) were in good agreement with literature results. By taking into account the URF, the flow pulsatility, the beam-to-flow angle and both the velocity and the ultrasound beam profiles, it was possible to explain all erratic FM signatures of a microbubble. Finally, by measuring FMI from simulated Doppler signals and by using a constant threshold of 1 KHz, it was possible to discriminate gaseous from solid microemboli with ease. (E-mail: jean-marc.girault@univ-tours.fr)     

益气活血法调节微栓子对脑梗死疗效的影响

目的 观察益气活血法对于微栓子（MES）阳性脑梗死患者的治疗效果.方法 将80例MES阳性脑梗死患者随机分为两组各40例.在内科、康复治疗基础上,治疗组给予中药益气活血法治疗,对照组给予安慰剂治疗.2周后测评日常生活活动量表（ADL）、Barthel指数（BI）记分.结果 治疗后两组MES数目明显减少（P＜0.01或P＜ 0.05）,且治疗组效果优于对照组（P＜0.05）.两组治疗后ADL量表评分均有显著改善（P＜0.01）.BI评级显示治疗组效果优于对照组（P＜0.05）.结论 中药益气活血法能明显减少缺血性脑卒中患者颅内微栓子数目,改善最终生存质量.     

急性缺血性卒中患者的经颅多普勒微栓子检测

目的：观察中国人急性缺血性卒中患者脑动脉微栓子信号（ＭＥＳ）的发生率及其临床意义。方法：采用双门深经颅多普勒（ＴＣＤ）监测１１５例大３脑中动脉（ＭＣＡ）区急性缺血性卒中患者双侧ＭＣＡ血流中的ＭＥＳ。结果：ＭＥＳ阳性发现率为４．３４％,在大血管脑梗塞组（１１．１１％）高于小血管脑梗塞组（６％）和ＴＩＡ组（３％）,在腔隙性脑梗塞组未发现ＭＥＳ。ＭＥＳ阳性发现率在有潜在的栓子来源的患者（９％）高于无栓子     

Transcranial Doppler and Microemboli Detection: Relationships to Symptomatic Status and Histopathology Findings

The purpose of this study was to determine the relationship between symptomatic status, transcranial Doppler (TCD) microemboli presence and plaque histopathology findings. TCD was performed on 60 patients (37 symptomatic, 23 asymptomatic) before undergoing clinically indicated carotid endarterectomy. The frequency of microemboli signals was not significantly different between symptomatic and asymptomatic subject groups (p = 0.88) and there were no differences observed in the macroscopic or histopathology scoring of these plaques (p-values all > 0.05). The presence of microemboli was associated with an ulceration score (regardless of symptomatic or asymptomatic status, p = 0.034), with a one-level increase in ulceration rating associated with an odds ratio of 5.86 (95% [CI] 1.55, 43.4). These findings suggest that both symptomatic and asymptomatic patients may have plaque with similar features of instability and ability to create emboli. Thus, identifying new ways to measure plaque instability may provide important information for optimizing treatment to prevent future stroke.