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.
OBJECTIVES: 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.
CONCLUSION: 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.