Résumé :
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The chronically failing heart is characterized by alterations in tissue structure, particularly fibrous tissue formation, responsible for the loss of myocardial compliance. Furthermore, rhythm disturbances are commonly observed. The underlying arrhythmogenic mechanisms are multiple, but myocardial fibrosis is frequently observed. Heart rate variability (HRV) reflects the functional status of the autonomic nervous system and its effects on sinus node. Considering autonomic dysfunction playing an important role in the pathogenesis and prognosis of congestive heart failure, HRV analysis may help to identify those who are at risk of cardiac death. Antifibrotic drugs may be considered for the treatment of heart failure. These experiments aimed at studying the diagnostic potential of HRV analysis to detect early modifications in cardiac electrical activity and at investigating the potential benefits of an antifibrotic treatment in CHF147 cardiomyopathic hamsters. HRV analysis was based on quantitative analysis of time series and allowed determining an early dysfunction in cardiac electrical activity in CHF147 cardiomyopathic hamsters. Pharmacological assays, coupled with HRV analysis allowed identifying a high sympathetic activity. Western blot and RT-PCR studies confirmed the neurovegetative imbalance. In a second set of experiment CHF147 hamsters were treated during 42 days with 3 different doses of Ac-SDKP or placebo, using osmotic minipumps. Weight and size of the ventricles were comparable in all groups. Ventricular fibrosis was quantified on Sirius red stained cryostat sections. Whereas fibrotic scar tissue remained comparable, interstitial fibrosis was significantly less pronounced in treated groups. This difference appeared to be more important for the lowest dose of Ac-SDKP. Histological results were confirmed by immunohistochemistery. Thus, HRV analysis appears to be an interesting tool for early diagnosis of cardiomyopathies, detecting decreased heart rate variability and activation of the sympathetic tone. Moreover, an antifibrotic treatment based on low doses of Ac-SDKP might be of therapeutic interest in cardiomyopathies.
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