Influence of microbubble surface charge on capillary transit and myocardial contrast enhancement

被引:101
作者
Fisher, NG [1 ]
Christiansen, JP [1 ]
Klibanov, A [1 ]
Taylor, RP [1 ]
Kaul, S [1 ]
Lindner, JR [1 ]
机构
[1] Univ Virginia, Cardiovasc Imaging Ctr, Div Cardiovasc, Charlottesville, VA 22903 USA
关键词
D O I
10.1016/S0735-1097(02)02038-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:811 / 819
页数:9
相关论文
共 27 条
[1]   Prolonged myocardial contrast echocardiography via peripheral venous administration of QW3600 injection (EchoGen(R)): Its efficacy and side effects [J].
Beppu, S ;
Matsuda, H ;
Shishido, T ;
Matsumura, M ;
Kiyatake, K .
JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, 1997, 10 (01) :11-24
[2]  
CHONN A, 1991, J IMMUNOL, V146, P4234
[3]  
CHONN A, 1992, J BIOL CHEM, V267, P18759
[4]  
Ciurea D, 1996, ANAT REC, V244, P182, DOI 10.1002/(SICI)1097-0185(199602)244:2&lt
[5]  
182::AID-AR6&gt
[6]  
3.0.CO
[7]  
2-3
[8]   LIPOSOME-COMPLEMENT INTERACTIONS IN RAT SERUM - IMPLICATIONS FOR LIPOSOME SURVIVAL STUDIES [J].
DEVINE, DV ;
WONG, K ;
SERRANO, K ;
CHONN, A ;
CULLIS, PR .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1994, 1191 (01) :43-51
[9]   Grafted poly-(ethylene glycol) on lipid surfaces inhibits protein adsorption and cell adhesion [J].
Du, H ;
Chandaroy, P ;
Hui, SW .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1997, 1326 (02) :236-248
[10]   Measurements of interbilayer forces and protein adsorption on uncharged lipid bilayers displaying poly(ethylene glycol) chains [J].
Efremova, NV ;
Bondurant, B ;
O'Brien, DF ;
Leckband, DE .
BIOCHEMISTRY, 2000, 39 (12) :3441-3451