Published Online
on May 6, 2002

A more recent version of this article appeared on June 11, 2002

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Submitted on February 28, 2002
Accepted on March 21, 2002

Left Ventricular Thrombus Enhancement After Intravenous Injection of Echogenic Immunoliposomes. Studies in a New Experimental Model

Andrew Hamilton MBBS^*, Shao-Ling Huang PhD, Drew Warnick BS, Adam Stein BS, Mark Rabbat BS, Taruna Madhav BA, Bonnie Kane BS, Ashwin Nagaraj PhD, Melvin Klegerman PhD, Robert MacDonald PhD, and David McPherson MD

From the Department of Medicine, Northwestern University, Chicago, Ill (A.H., D.W., A.S., M.R., T.M., B.K., A.N., D.M.); Echodynamics, College Park, Md (M.K.); and the Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Ill (S.-L.H., R.M.).

^* To whom correspondence should be addressed. E-mail: a-hamilton{at}northwestern.edu.

Background—Targeted echogenic immunoliposomes (ELIPs) for ultrasound enhancement of atheroma components have been developed. To date, ELIP delivery has been intra-arterial. To determine whether ELIPs can be given intravenously with enhancement of systemic structures, a left ventricular thrombus (LVT) model was developed.

Methods and Results—In 6 animals plus 1 dose-ranging animal, the apical coronary arteries were ligated, and an LVT was produced by injecting Hemaseel fibrin adhesive through the apical myocardium. The thrombus was imaged epicardially and transthoracically at 0, 1, 5, and 10 minutes after anti-fibrinogen ELIP injections. The dose of ELIPs was varied. PBS and unconjugated ELIPs were controls. The apical thrombi were easily reproduced and clearly visible with epicardial and transthoracic ultrasound. Enhancement occurred with 2 mg anti-fibrinogen ELIPs and increased with dose. With 8 mg ELIPs, enhancement was different from control within 10 minutes (P<0.05). Rhodamine-labeled anti-fibrinogen ELIPs were seen with fluorescence microscopy of the LVT. Blinded viewing detected enhancement by 10 minutes in all animals after anti-fibrinogen ELIPs.

Conclusions—We describe an easily reproducible LVT model. Anti-fibrinogen ELIPs delivered intravenously, as a single-step process, rapidly enhance the ultrasound image of a systemic target. This allows for future development of ELIPs as a targeted ultrasound contrast agent.

Key words: echocardiography • contrast media • thrombus

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