Faculty Collaboration Database

Early detection of doxorubicin cardiomyopathy using two-dimensional strain echocardiography. Ultrasound Med Biol 2008 Feb;34(2):208-14

Date

10/16/2007

Pubmed ID

17935867

Pubmed Central ID

PMC2582214

DOI

10.1016/j.ultrasmedbio.2007.07.018

Scopus ID

2-s2.0-38349141345 (requires institutional sign-in at Scopus site)   105 Citations

Abstract

Doxorubicin is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiomyopathy that may lead to heart failure. Conventional measures of ventricular function, such as fractional shortening, are insensitive in detecting early doxorubicin cardiomyopathy. We tested whether novel two-dimensional radial strain echocardiography (2DSE) can detect early doxorubicin injury following chronic administration in a rat model. 14 male Sprague Dawley rats (240 to 260 g) received doxorubicin 2.5 mg/k i.v. per wk for 10 (n=4) or 12 wk (n=10); 17 controls received saline (10 wk, n=7 and 12 wk, n=10). Serial 2DSE from 0 to 12 wk was done at the mid left ventricle using Vivid 7 echo (General Electric, Waukesha, WI, USA). With Q analysis software, radial strain was obtained. From the two-dimensional (2D) image, anatomical M-mode through the anterior/inferior walls was used to measure fractional shortening. Fibrosis (Masson's trichrome) and caspase-3 activity were measured from excised hearts. Radial strain was lower in the doxorubicin group (12 wk: 26.7+/-3 versus 38.3+/-2.6%, p=0.006), with significant difference by 8 wk whereas fractional shortening was lower with doxorubicin only after 12 wk (30.2+/-1.7 versus 37.6+/-1.4%, p=0.02). Doxorubicin group had lower cardiac mass (0.85+/-0.09 versus 1.14+/-0.04 g, p=0.001), higher caspase-3 activity (1.95+/-0.2 fold increase over control, p<0.0001) and fibrosis (3.9 +/- 0.7 versus 0.7+/-0.1%, p=0.005). Radial strain was related directly to cardiac mass (r=0.61, p=0.0007) and inversely to caspase-3 activity (r= -0.5, p=0.005). 2-dimensional radial strain echocardiography is useful in the early detection of doxorubicin cardiac injury and the reduction in radial strain is associated with histologic markers of doxorubicin cardiomyopathy.

Author List

Migrino RQ, Aggarwal D, Konorev E, Brahmbhatt T, Bright M, Kalyanaraman B

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antibiotics, Antineoplastic
Doxorubicin
Echocardiography, Stress
Fibrosis
Heart Diseases
Heart Failure
Image Interpretation, Computer-Assisted
Male
Models, Animal
Myocardium
Rats
Rats, Sprague-Dawley
Staining and Labeling
Ventricular Dysfunction, Left