Circulation · 2003 · 254 citations · 22 references
MedicineCardiologyImmunologyCardiac TransplantationUltrasonographyUltrasoundAcute RejectionCardiac UltrasoundCell Adhesion ReceptorsContrast-enhanced UltrasonographyContrast-enhanced UltrasoundTransplant RejectionAcute Cardiac Allograft RejectionAcute Rejection DetectionIntercellular Adhesion Molecule 1Intracardiac EchocardiographyMicrobubble Contrast ImagingMyocardial Inflammation DetectionUltrasound Contrast AgentsUltrasound Imaging Of Inflammation
Noninvasive techniques for detecting acute cardiac transplant rejection are limited. The study hypothesizes that ICAM‑1‑targeted microbubbles will selectively bind to rejecting myocardium and that myocardial contrast echocardiography can detect acute rejection, offering a noninvasive imaging approach for endothelial dysfunction. Lipid microbubbles were conjugated to anti‑ICAM‑1 or isotype control antibodies, heterotopic heart transplants were performed in rats, and myocardial contrast echocardiography was conducted on postoperative day 5 after intravenous injection of the microbubbles. In vitro, ICAM‑1‑targeted microbubbles adhered more to inflamed endothelial cells, and in vivo, myocardial contrast echocardiography revealed significantly higher videointensity in rejecting hearts versus controls, with histology confirming grade III–IV rejection and strong ICAM‑1 expression, demonstrating preferential ultrasound detection of rejection.
Noninvasive techniques for detecting acute cardiac transplant rejection are limited. We hypothesized that ultrasound contrast microbubbles targeted to the endothelial cell (EC) inflammatory marker intercellular adhesion molecule-1 (ICAM-1) would selectively bind to rejecting versus nonrejecting myocardium and that myocardial contrast echocardiography can therefore detect acute rejection.Lipid-based microbubbles were conjugated to anti-rat ICAM-1 (MBICAM) or isotype control antibody (MBControl). In vitro MBICAM adhesion to cultured rat ECs, as assessed in a parallel plate flow apparatus, was greater to inflammatory versus normal ECs (11+/-3 versus 3+/-2 microbubbles/EC, P<0.005). In vivo abdominal heterotopic heart transplantation was performed in rats (rejection group: Brown Norway to Lewis strain; control group: Lewis to Lewis or Brown Norway to Brown Norway). Triggered myocardial contrast echocardiography was performed during intravenous MBICAM or MBControl (2.5x10(6)) injection on postoperative day 5. Myocardial videointensity from adhered MBICAM was significantly higher in rejecting (n=8) versus control (n=7) rats (10+/-4 versus 1+/-4 U, P=0.01). Postmortem histology showed normal myocardium in control rats, whereas allograft myocardium demonstrated grade III to IV rejection and strong immunohistochemical ICAM-1 staining.Preferential adherence of ICAM-1-targeted microbubbles to rejecting versus nonrejecting rat cardiac transplant myocardium can be detected ultrasonically. Targeted microbubbles may thus offer a noninvasive ultrasound imaging technique for the detection of acute cardiac transplant rejection and other processes characterized by endothelial dysfunction.
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Margaret E. Billingham, N. Cary, M. Elizabeth Hammond et al. · PubMed · 1991 · 1.5K citations
Medicine, Cardiology, Pathology +15