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Cardiac Arrhythmia and Injury Induced in Rats by Burst and Pulsed Mode Ultrasound With a Gas Body Contrast Agent

Departments of Radiology (D.L.M., C.D.) and Pharmacology (B.R.L.), University of Michigan, Ann Arbor, Michigan USA.

Address correspondence to Douglas L. Miller, PhD, University of Michigan Health System, 3240A Medical Sciences Building I, 1301 Catherine St, Ann Arbor, MI 48109-5667 USA., E-mail: douglm{at}umich.edu

Objective. Premature complexes (PCs) in the electrocardiogram (ECG) signal have been reported for myocardial contrast echocardiography and also for burst mode (physical therapy) ultrasound with gas body contrast agents at lower peak rarefactional pressure amplitudes (PRPAs). For contrast echocardiography, irreversibly injured cardiomyocytes have been associated with the arrhythmia. The objective was to determine whether cardiomyocyte injury is associated with the PCs induced by the burst mode at lower PRPAs. Methods. Anesthetized rats were exposed to focused 1.5-MHz ultrasound in a water bath. Evans blue dye was injected intraperitoneally to stain injured cardiomyocytes, and a perflutren lipid microsphere ultrasound contrast agent was infused intravenously. The continuous burst mode simulated physical therapy ultrasound. Intermittent 2-millisecond bursts, or envelopes of pulses simulating diagnostic ultrasound, were triggered 1:4 at end systole. Premature complexes were observed on ECG recordings, and stained cardiomyocytes were counted in frozen sections. Results. The continuous burst mode produced variable PCs and stained cells above a 0.3-MPa PRPA. The triggered bursts above 0.3 MPa and pulse envelopes above 1.2 MPa produced statistically significant (P < .01) PCs and stained cardiomyocytes. Conclusions. Irreversible cardiomyocyte injury was associated with the development of PCs for the burst mode and occurred at substantially lower PRPAs than for pulsed ultrasound.

Key Words: arrhythmia • contrast agent adverse effects • gas body activation • myocardial contrast echocardiography • ultrasonic cavitation biology

Abbreviations: ECG, electrocardiogram • PC, premature complex • PRPA, peak rarefactional pressure amplitude • PVC, premature ventricular complex • SC, stained cell • SPC, supraventricular premature complex