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European Heart Journal Advance Access published online on September 15, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi479
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received March 25, 2005
Revised July 28, 2005
Accepted August 11, 2005

Preclinical research

Myocardial delivery of colloid nanoparticles using ultrasound-targeted microbubble destruction

David Vancraeynest 1, Xavier Havaux 1, Anne-Catherine Pouleur 1, Agnès Pasquet 1, Bernhard Gerber 1, Christophe Beauloye 1, Patrick Rafter 1, Luc Bertrand 1, and Jean-Louis J. Vanoverschelde 1*

1 Division of Cardiology, Cliniques Universitaires St-Luc, Université catholique de Louvain, Avenue Hippocrate, 10-2881, B-1200 Brussels, Belgium

* To whom correspondence should be addressed.
Jean-Louis J. Vanoverschelde, E-mail: vanoverschelde{at}card.ucl.ac.be


  Abstract

Aims Ultrasound (US)-targeted microbubble destruction (UTMD) is a promising method for delivering genetic material to the heart. The aim of this study was: (i) to test whether colloid nanoparticles can be delivered to the rat myocardium using UTMD; and (ii) to determine whether tissue damage and contractile dysfunction occurs in hearts exposed to UTMD in vivo.

Methods and results Hearts from anaesthetized rats were exposed to perfluorocarbon-enhanced sonicated dextrose albumin (PESDA) (at two different microbubble concentrations) and US at peak pressures of 0.6, 1.2, or 1.8 MPa for 1, 3, or 9 min. During US, pairs of 30 and 100 nm fluorescent nanospheres were infused intravenously. Left ventricular function was assessed before and immediately after US, as well as at 24 h and 7 days. At the end of the experiments, the number of ruptured microvessels and the amount of nanospheres deposited were quantified. Rats exposed to PESDA alone or US alone showed no functional abnormalities, no capillary ruptures, and no nanosphere delivery. In contrast, rats exposed to both PESDA and US exhibited microvascular ruptures and nanosphere deposits. They also showed transient contractile dysfunction and premature ventricular contractions. All these changes were time-, US peak pressure-, and PESDA concentration-dependent.

Conclusion UTMD allows colloid nanoparticles to be delivered to the rat myocardium through microvessel rupture sites. The efficacy of delivery depends on the peak pressure applied, the duration of US exposure, and contrast concentration. UTMD also causes time- and peak pressure-dependent contractile dysfunction, and tissue alterations that are spontaneously reversible over time.

Keywords: Contrast echocardiography; Local delivery.
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D. Vancraeynest, J. Kefer, C. Hanet, C. Fillee, C. Beauloye, A. Pasquet, B. L. Gerber, M. Philippe, and J.-L. J. Vanoverschelde
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Eur. Heart J., May 2, 2007; 28(10): 1236 - 1241.
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