Microbubble Mediated Thrombus Dissolution with Diagnostic Ultrasound for the Treatment of Chronic Venous Thrombi

被引:19
作者
Kutty, Shelby [1 ]
Wu, Juefei [2 ]
Hammel, James M. [3 ]
Xie, Feng [2 ]
Gao, Shunji [2 ]
Drvol, Lucas K. [2 ]
Lof, John [2 ]
Radio, Stanley J. [4 ]
Therrien, Stacey L. [2 ]
Danford, David A. [1 ]
Porter, Thomas R. [2 ]
机构
[1] Creighton Univ, Childrens Hosp & Med Ctr, Univ Nebraska Coll Med, Joint Div Pediat Cardiol, Omaha, NE 68178 USA
[2] Univ Nebraska Med Ctr, Dept Internal Med, Cardiol Sect, Omaha, NE USA
[3] Univ Nebraska Med Ctr, Div Cardiovasc Surg, Omaha, NE USA
[4] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA
基金
美国国家卫生研究院;
关键词
CAVITATIONAL MECHANISMS; DIALYSIS GRAFTS; THROMBOEMBOLISM; COMPLICATIONS; THERAPY;
D O I
10.1371/journal.pone.0051453
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo. Methods and Results: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. A thrombus was then allowed to form and age over 24 hours. The created thrombus was localized and measured by ICE, and transthoracic image guided high mechanical index (MI) two-dimensional US treatments (1.1-1.7 MI; iE33, Philips) applied intermittently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 10; Group A). Control pigs (n = 10; Group B) received US without MB. All treatments were randomized. Post-treatment thrombus area by ICE planimetry was compared with pretreatment measurements. Thrombus area measurements before and after treatment were 0.22 and 0.10 cm(2) respectively in Group A; compared to 0.24 and 0.21 cm(2) in Group B (p = 0.0003). Effectiveness of longer duration US and MB thrombolytic treatments were studied (n = 4), which suggested that near complete thrombus dissolution is possible. No pulmonary emboli, alterations in oxygen saturation, or hemodynamics occurred with either treatment. Conclusions: Guided high MI diagnostic US+systemic MB facilitates reduction of aged CVC associated thrombi in vivo. MB enhanced sonothrombolytic therapy may be a non-invasive safe alternative to thrombolytic agents in treating thrombotic CVC occlusions.
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页数:11
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