Drug found to reduce fibrosis in a rat heart failure model with myocardial infarction

Drug found to reduce fibrosis in a rat heart failure model with myocardial infarction

30 Jan Drug found to reduce fibrosis in a rat heart failure model with myocardial infarction

Congestive heart failure (CHF) is a serious outcome of myocardial infarction (MI). It is often associated with severe structural and functional changes of the atria, among which fibrosis, contributing to impaired atrial function and the risk of arrhythmia. Fibrosis is the formation of excess fibrous connective tissue in a reparative or reactive process, and can be observed during CHF in both animal models and human biopsies. CHF is also associated with abnormalities of cell electrophysiology. This remodelling of the heart’s atria is likely responsible for atrial fibrillation (AF), the incidence of which is increased during CHF.

French and Italian researchers, looked into the prevention or reversion of this atrial remodelling associated with CHF. They examined whether treatments currently used for CHF, such as spironolactone, ACE-inhibitors, and beta-blockers, can reverse atrial remodelling. To do so, they used a rat model of MI complicated by left ventricular dysfunction, in which the left atria remodelling and severe fibrosis occur within 3 months after MI. Three months after MI, the rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. They were monitored using Echocardiography–Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring which also helped characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining.

Three months after surgery, sham-operated rats displayed normal echocardiographic parameters, whereas MI rats showed clear signs of LV dysfunction. Their left atrial diameter increased, as did atrial fibrosis. Moreover, premature atrial beats became frequent and P-wave duration was also increased. After a 1-month treatment with either spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination improvements in left ventricular dysfunction were observed. Atrial hyperexcitability was reduced by all the treatments.

Surprisingly, attenuation of LV dysfunction in treated rats with MI was not always associated with the regression of atrial myocardium remodelling. Only spironolactone, used alone or in combination with other drugs, induced a significant decrease in atrial fibrosis. The mechanisms by which spironolactone reduces fibrosis are not fully understood yet. However, the fact that spironolactone has a marked efficacy on the structural remodelling of the atrial myocardium suggests that clinical studies may be the next step to determine whether antifibrotic treatment might open new therapeutic perspectives for both the prevention and treatment of AF.


European Heart Journal (2005) 26, 2193–2199 doi:10.1093/eurheartj/ehi478


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, rat model, good model, ventricle, myocardial infarction, Congestive heart failure, fibrosis, atria dysfunction

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