Douglas Miller PhD, Presenter: Nothing to Disclose

Peng Li MD, Abstract Co-Author: Nothing to Disclose

David Gordon MD, Abstract Co-Author: Nothing to Disclose

William Armstrong MD, Abstract Co-Author: Nothing to Disclose

Arrhythmias and histologically defined microlesions have been reported following myocardial contrast echocardiography (MCE) in rats. This research examined the relationship of these effects to specific cardiomyocyte injury.

A 1.5 MHz cardiac imaging system (GE Vingmed System V) was used to perform MCE with 1:4 ECG triggering in anesthetized rats mounted in a water bath. The ultrasonic peak rarefactional pressure amplitudes were measured and corrected for attenuation to provide accurate Mechanical Index (MI) values. A 5 min infusion of Definity® ultrasound contrast agent was given at 10 μl/kg/min diluted 50:1 in saline via tail vein at the beginning of 10 min of MCE. Evans blue dye was injected as an indicator of cardiomyocyte death. Premature beats were counted from the ECG record. Wax sections were stained for DNA breaks (Apoptag® apoptosis detection kit, Serologicals Corp.) in sham, 4 hr and 24 hr post MCE hearts. Necrotic cells indicated by fluorescent Evans blue staining were counted on frozen sections of heart samples obtained 24 hr post MCE.

Essentially no effects were seen for sham MCE. Premature beats (47±21 for n=6 at 1.6 MI) were noted during MCE. Apoptag® stained nuclei were found concentrated within the anterior myocardium at 4 hr, but diminished in number by 24 hr. Evans blue fluorescent cells (373±200 for n=6 at 1.6 MI) were evident in similar regions at 24 hr and their number was not significantly different from the apoptotic cell counts at 4 hr. For end systolic triggering, premature beats and fluorescent cells both increased with MI values above 0.9, with similar exposure-response trends (correlation coefficient r˛=0.63). The numbers of fluorescent cells were not significantly different for end diastolic triggering.

Cardiomyocyte injury during MCE induces acute cell death leading to inflammatory cell infiltration, and is associated with premature beats. This cell death is consistent with programmed cell death (apoptosis), although other pathways to cell death may be at play. Minimal efficacious contrast agent doses and MI settings should be utilized to maximize the safety profile of MCE.

Miller, D, Li, P, Gordon, D, Armstrong, W, Arrhythmia and Cell Death Induced by Myocardial Contrast Echocardiography in Rats.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4405649.html