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Arrhythmias in Rat Hearts Exposed to Pulsed Ultrasound After Intravenous Injection of a Contrast Agent

Bioengineering Program, University of Illinois at Urbana-Champaign (J.F.Z., L.A.F., W.D.O.), Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering, University of Illinois (S.A.H., L.A.F., W.D.O.), Urbana, Illinois.

Address correspondence and reprint requests to James F. Zachary, DVM, PhD, University of Illinois, 2001 S Lincoln Ave, Urbana, IL 61802.

Objective. To develop an animal model suitable for characterizing electrocardiographic arrhythmias in hearts exposed to ultrasound after injection of a microbubble contrast agent. Methods. Conduction complex and heart lesion data were recorded from 20 rats that received intravenous injections of 0.25 mL of a contrast agent and were exposed to pulsed ultrasound (frequency, 3.1 MHz; pulse duration, 1.3 microseconds; pulse repetition frequency, 1700 Hz; and in situ peak rarefactional pressure, 15.9 MPa). The volume of the contrast agent based on body weight and the mechanical index (ultrasonic pressure) exceeded those used in echocardiography by 14 to 345 and 3 to 29 times, respectively. Results. Premature atrial complexes, premature ventricular complexes, or polymorphic ventricular tachycardia occurred in 10 rats. When ultrasound exposure was halted, arrhythmias ceased but reoccurred in 4 of the 10 rats when exposure resumed. Myocardial degeneration identified by histochemical staining (hematoxylin-basic fuchsin-picric acid) was observed in 16 rats; however, only 10 rats had arrhythmias. There was no significant difference in the amount of histochemical staining in hearts from rats with arrhythmias when compared with rats without arrhythmias. Conclusions. An animal model suitable for characterizing electrocardiographic arrhythmias in rat hearts exposed to ultrasound after injection of a microbubble contrast agent was developed. Because arrhythmias were induced principally when the contrast agent interacted with ultrasound during exposure, the presence of myocardial degeneration alone was not a sufficient explanation for ectopic electrical activity. Under these extreme exposure conditions, the data suggest that pulsed ultrasound through its biomechanical interactions with contrast agents has the potential to induce arrhythmias.

Key Words: arrhythmias • conduction abnormalities • contrast agent • pulsed ultrasound

Abbreviations: FDA, Food and Drug Administration • HBFP, hematoxylin-basic fuchsin-picric acid • MI, mechanical index

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