Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement
Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement
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DOI：
10.1016/s0735-1097(02)02038-7
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发表时间：
2002-08-21
影响因子：
24
通讯作者：
Lindner, JR
中科院分区：
文献类型：
--
作者：
Fisher, NG;Christiansen, JP;Lindner, JR
目的研究微泡电荷是否影响微泡造影剂的微血管滞留。背景：与中性膜相比，阴离子造影剂与血清蛋白之间的相互作用更强。这些相互作用可能影响阴离子脂质微泡的微血管行为。方法在6只野生型小鼠和3只C3缺陷小鼠静脉注射中性或负电荷的脂壳微泡的过程中，对提睾肌进行活体显微镜观察。这两种试剂都是在有和没有聚乙二醇表面层保护的情况下制备的。用异硫氰酸荧光素标记的抗C3b单抗，用流式细胞术检测补体在微泡上的黏附情况。对6只犬进行了心肌声学造影检查，以评估微泡在肺和心肌中的滞留。结果微泡的大小无关的毛细血管滞留在阴离子微泡中持续几秒钟至10分钟，但很少在中性微泡中观察到(4.3+/-0.3vs.0.4+/-0.1 mm(-3)，p<；0.01)。表面聚乙二醇组的阴离子微泡保留减少了70%，在C3缺乏的小鼠(1.4+/-0.1 mm(-3)，p<；0.05与野生型相比)也显著减少。流式细胞术显示补体仅附着在阴离子微泡上。超声心动图显示肺和心肌仅有阴离子微泡滞留，后者在静脉推注后10分钟出现持续性浑浊。结论补体介导的内皮附着可使带净负电荷的脂质微泡滞留在毛细血管内。这一特性可能有助于开发可以在静脉注射后晚些时候成像的超声造影剂。(C)2002年，由美国心脏病学会基金会提供。
OBJECTIVE The goal of the study was to determine whether microbubble charge influences the microvascular retention of microbubble contrast agents.BACKGROUND Interactions between serum proteins and lipid membranes are greater with anionic compared with neutral membranes. These interactions may influence the microvascular behavior of anionic lipid microbubbles.METHODS Intravital microscopy of the cremaster muscle was performed in six wild-type mice and three C3-deficient mice during intravenous injection of lipid-shelled microbubbles with either a neutral or a negative charge. Both agents were prepared with and without a protective surface layer of polyethyleneglycol (PEG). Complement attachment to microbubbles was assessed by flow cytometry with flourescein isothiocyanate-conjugated anti-C3b monoclonal antibody. Myocardial contrast echocardiography was performed in six dogs to assess pulmonary and myocardial retention of microbubbles.RESULTS Size-independent capillary retention of microbubbles, occurring for a few seconds to >10 min, was frequently observed with anionic, but rarely with neutral, microbubbles (4.3 +/- 0.3 vs. 0.4 +/- 0.1 mm(-3), p < 0.01). Anionic microbubble retention was reduced by 70% by surface PEG and was also markedly reduced in C3-deficient mice (1.4 +/- 0.1 mm(-3), p < 0.05 vs. wild-type). Flow cytometry demonstrated complement attachment to only anionic microbubbles. Contrast echocardiography indicated both pulmonary and myocardial retention of only anionic microbubbles, the latter evidenced by persistent opacification >10 min after bolus intravenous injection.CONCLUSIONS Lipid microbubbles with a net negative charge can be retained within capillaries via complement-mediated attachment to endothelium. This property may be useful for the development of ultrasound contrast agents that can be imaged late after venous injection. (C) 2002 by the American College of Cardiology Foundation.