Echocardiographic preclinical studies of Congestive heart failure

Congestive heart failure (CHF) is a serious outcome of myocardial infarction (MI). Animal models have been used to study various aspects of CHF. Postinfarction animal models have been extensively studied because myocardial ischemia and infarction are frequent causes of CHF in humans. However, not all post infarction hearts undergo transition to CHF.

In many studies in rats, echocardiographic validation of the model has not been performed, and, consequently, there are no data that allow assessment of the degree of contractile failure. In studies of possible cellular dysfunction in heart failure after MI, it is clearly essential to select animals that have a safe diagnosis of CHF.

It is generally acknowledged that left ventricular dilatation occurs mainly after large transmural infarctions. Traditionally, because it reflects preload, left ventricular end diastolic pressure has been used as a main criterion of diagnosis of CHF in rats. However, this technique may cause damage to the aortic valves and affect cardiac performance. Echocardiography is a non-invasive alternative approach that may be used to very CHF diagnosis. Researchers decided to evaluate the postinfarction myocardial function in rats and determined echocardiographic criteria for CHF using high performance echocardiography.

Extensive MI was induced in rats by left coronary occlusion and five weeks later, high-frame rate (∼200 Hz), fully digitized, shallow-focus (10–25 mm), two-dimensional, M-mode and Doppler echocardiography was performed.

Because experiments on papillary muscle strips and isolated cardiomyocytes from CHF rats in overt failure, have shown that shortening velocity is substantially reduced the researchers hypothesized that left ventricular wall shortening velocity may be a valid and reliable criterion for CHF.

Animals were examined for clinical signs of CHF and the researchers looked for the echocardiographic measure that best separated the various clinical signs. That measure became the optimal criterion for distinguishing failing rats from nonfailing and sham-operated rats.

Two type of MI induced responses seemed to be clearly visible, one of which had clinical characteristics of CHF and elevated left ventricular end diastolic pressure. Among the echocardiographic variables, only posterior wall shortening velocity separated the failing and nonfailing responses.

It is therefore possible to obtain by high frame rate echocardiography, high- quality recordings in rats, to distinguish MI rats with CHF due to myocardial dysfunction from those without failure and to perform longitudinal studies on myocardial function.

Syncrosome, a scientific preclinical CRO based in France, also uses a rat with Chronic coronary ligature to model Heart failure for efficacy testing. They monitor, Doppler echocardiography, Coronary artery ligation, reperfusion, blood pressure, heart rate, planimetry, histology and morphological and functional biomarkers. By combining all these parameters, they can most reliably test for appropriate reaction.


Key words: preclinical CRO, preclinical study, animal model, animal research, myocardial, heart failure, infarction, echocardiography, heart, porcine model, rat model, god model, ventricle, myocardial infarction, Congestive heart failure