Maturation of Lesions Induced by Myocardial Cavitation-Enabled Therapy

Myocardial contrast echocardiography at enhanced therapeutic parameters may be a novel means of tissue reduction therapy, as for hypertrophic cardiomyopathy. Dahl/SS rats were anesthetized and treated with high-amplitude pulsed ultrasound guided by 10-MHz ultrasound images. Contrast microbubbles were infused via the tail vein during intermittent pulse-burst exposure at 4 MPa. A sham group, a low-impact group (group A, 5 cycle pulses with Gaussian modulation and 1:4 trigger for 5 min) and a high-impact group (group B, 10 cycle pulses with 4-ms square modulation and 1:8 trigger for 10 min) were tested. The higher exposure used in group B yielded more substantial injury than the lower exposure in group A. Treated rats in both groups A and B had significant increases in wall thickness measured by echocardiography the next day, which returned to normal by the end of 6 wk. Six weeks after ultrasound exposure, heart tissue samples exhibited tissue fibrosis in Masson's trichrome stained histology. Maturation of lesions involved fibrosis replacement, preserving structural tissue integrity. This study indicates that myocardial injury noted previously progresses into permanent loss of myocardial tissue that may be sufficient for possible hypertrophic cardiomyopathy therapy. More research is needed to define the treatment parameters required for symptomatic relief for hypertrophic cardiomyopathy.