Acoustic Activation Imaging With Intravenous Perfluoropropane Nanodroplets Results in Selective Bioactivation of the Risk Area

Author:

Li Shouqiang12,Chen Cheng3,Lof John2,Stolze Elizabeth A.2,Sklenar Jiri4,Chen Xucai3,Pacella John J.3,Villanueva Flordeliza S.3,Matsunaga Terry O.5,Everbach E. Carr6,Radio Stanley J.7,Westphal Sherry N.2,Shiva Sruti8,Xie Feng2,Leng Xiaoping1,Porter Thomas R.2ORCID

Affiliation:

1. Department of Ultrasound Second Affiliated Hospital of Harbin Medical University Harbin China

2. Division of Cardiovascular Medicine University of Nebraska Medical Center Omaha Nebraska USA

3. Center for Ultrasound Molecular Imaging and Therapeutics University of Pittsburgh Pittsburgh Pennsylvania USA

4. narnar.co Lake Oswego Oregon USA

5. Department of Biomedical Engineering University of Arizona Tucson Arizona USA

6. Department of Engineering Swarthmore College Swarthmore Pennsylvania USA

7. Department of Pathology and Microbiology University of Nebraska Medical Center Omaha Nebraska USA

8. Department of Pharmacology and Chemical Biology, Molecular Medicine Institute University of Pittsburgh Pittsburgh Pennsylvania USA

Abstract

BackgroundAcoustically activatable perfluoropropane droplets (PD) can be formulated from commercially available microbubble preparations. Diagnostic transthoracic ultrasound frequencies have resulted in acoustic activation (AA) predominately within myocardial infarct zones (IZ).ObjectiveWe hypothesized that the AA area following acute coronary ischemia/reperfusion (I/R) would selectively enhance the developing scar zone, and target bioeffects specifically to this region.MethodsWe administered intravenous PD in 36 rats and 20 pigs at various stages of myocardial scar formation (30 minutes, 1 day, and 7 days post I/R) to determine what effect infarct age had on the AA within the IZ. This was correlated with histology, myeloperoxidase activity, and tissue nitrite activity.ResultsThe degree of AA within the IZ in rats was not associated with collagen content, neutrophil infiltration, or infarct age. AA within 24 hours of I/R was associated with increased nitric oxide utilization selectively within the IZ (P < .05 compared with remote zone). The spatial extent of AA in pigs correlated with infarct size only when performed before sacrifice at 7 days (r = .74, P < .01).ConclusionsAcoustic activation of intravenous PD enhances the developing scar zone following I/R, and results in selective tissue nitric oxide utilization.

Funder

National Institutes of Health

Publisher

Wiley

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