A small animal model of non-ischemic cardiomyopathy and its evaluation by transthoracic echocardiography.
BACKGROUND
Costs for large animal studies have escalated. Therefore there is a need to develop small animal models of non-ischemic cardiac failure and accurate non-invasive techniques that will allow serial quantitation of left ventricular function.


OBJECTIVE
The purpose of our study was to determine the efficacy and reliability of adriamycin for inducing cardiomyopathy in rats. We hypothesized that high frequency transthoracic 2-dimensional and M-mode echocardiography would allow for serial testing of cardiac function in this small animal model.


METHODS
Adriamycin was administered at a dose of 2.5 mg/kg intravenously once a week for 10 weeks in 54 rats. Transthoracic echocardiography by use of a 7.5 MHz transducer was performed in 19 rats at baseline and additionally at 12 weeks after beginning of adriamycin therapy to measure left ventricular dimensions and calculate fractional shortening.


RESULTS
The mortality rate during the treatment period was 11%, but increased to 52% at 13 weeks. Transthoracic echocardiography provided adequate visualization of left ventricular dimensions and cardiac function in a parasternal short axis view. In follow-up echocardiography, pericardial effusion was detected in 8/19 rats (42%). Compared to baseline, end-diastolic diameters increased from 0.56 +/- 0.06 to 0.64 +/- 0.08 mm (p < 0.001), end-systolic diameters increased from 0.27 +/- 0.03 to 0.42 +/- 0.08 mm (p < 0.001), and fractional shortening decreased from 52.8 +/- 4.0 to 34.3 +/- 7.1% (p < 0.001) at 12 weeks. Electron microscopy in a subset of rats revealed cardiomyocyte degeneration, mitochondrial and sarcoplasmatic reticular edema, numerous intracellular vacuoles and 'onion-ring' shaped mitochondrial cristae, characteristic for adriamycin cardiotoxicity in human patients.


CONCLUSIONS
Adriamycin at an intravenous dose of 2.5 mg/kg over 10 weeks can be used to create a reliable model of non-ischemic dilated cardiomyopathy with a high success rate. For in-vivo diagnostic purposes, transthoracic echocardiography provides a reliable technique to non-invasively assess cardiac function quantitatively and qualitatively in follow-up studies in rat cardiomyopathy. This small animal model can easily be used for testing new therapeutic strategies in cardiac failure.
Heart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA.
E R
ER
Schwarz
C
C
Pollick
J
J
Dow
M
M
Patterson
Y
Y
Birnbaum
R A
RA
Kloner
D000818:Animals; D000903:Antibiotics, Antineoplastic; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000473:pathology; D004195:Disease Models, Animal; D004317:Doxorubicin; D004452:Echocardiography; D005069:Evaluation Studies as Topic; D005260:Female; D008854:Microscopy, Electron; D009206:Myocardium / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin