The long term objective of this project is to utilize the multiple therapeutic properties of perfluorocarbon containing albumin coated microbubbles to non-invasively target synthetic gene therapy and recanalize thrombosed access grafts and coronary arteries. The ability of intravenous perfluorocarbon containing albumin microbubbles to bind and deliver antisense oligonucleotides to the c-myc protoncogene into the endothelium following intracoronary stent deployment will be quantified, and then tested in humans to determine whether it significantly reduces restenosis. Secondly, the ability of these intravenous microbubbles to microfragment arterial thrombi in the presence of low frequency ultrasound will be prospectively evaluated to determine whether it can replace current pharmacologic and surgical techniques in recanalizing thrombosed renal dialysis grafts. The ability of perfluorocarbon containing microbubbles to both recanalize acute coronary thromboses and diffuse oxygen from the lungs to ischemic tissue will be combined to determine how these properties can improve the clinical outcome of patients with acute coronary syndromes. Finally, the ability of perfluorocarbon containing microbubbles to induce atrial and ventricular paced rhythms in the presence of low frequency ultrasound will be assessed in patients undergoing electrophysiologic testing. These multi-faceted investigations will provide the framework for the use of microbubbles as an alternative or supplement to current cardiovascular therapies.
In addition to diagnostic applications, perfluorocarbon containing albumin microbubbles may have several therapeutic applications. First, they could be a noninvasive method of targeting the delivery of specific intravenous antisense oligonucleotides to damaged endothelium. They can also target the delivery of oxygen to ischemic tissue. In the presence of transcutaneous low frequency ultrasound, they cavitate and break up intra arterial thrombi. Therefore, they may be an alternative or supplement to fibrinolytic therapy in treating hemodialysis access graft thrombosis or acute coronary syndromes.
| Porter, Thomas R; Xie, Feng; Knapp, Derek et al. (2006) Targeted vascular delivery of antisense molecules using intravenous microbubbles. Cardiovasc Revasc Med 7:25-33 |
| Chapman, Scott; Windle, John; Xie, Feng et al. (2005) Incidence of cardiac arrhythmias with therapeutic versus diagnostic ultrasound and intravenous microbubbles. J Ultrasound Med 24:1099-107 |
| Porter, T R; Kricsfeld, D; Lof, J et al. (2001) Effectiveness of transcranial and transthoracic ultrasound and microbubbles in dissolving intravascular thrombi. J Ultrasound Med 20:1313-25; quiz 1326 |
| Culp, W C; Porter, T R; Xie, F et al. (2001) Microbubble potentiated ultrasound as a method of declotting thrombosed dialysis grafts: experimental study in dogs. Cardiovasc Intervent Radiol 24:407-12 |
