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Title: The therapeutic efficacy of the renin–angiotensin–aldosterone system inhibition on myocardial function in amurine model of dilated cardiomyopathy (Tg_x0006_q*44 mice)
Abstract:
The Tgαq*44 mice exhibit a unique animal model of HF in which the overexpression of active αq subunit of the G protein in cardiomyocytes mimic persistent receptor (adrenergic α1,angiotensin AT1, endothelin ET-A) stimulates and activates the intracellular signal pathways. These intracellular pathways are known to play key roles in the pathogenesis of the heart hypertrophy and cause heart failure in humans. The purpose of this study was to assess the effect of two month therapy with angiotensin-converting enzyme inhibitor (ACE-I) and aldosterone receptor antagonist (ARA) on left ventricle functions in Tgαq *44 mice. In the course of this study, the ACE inhibitor (perindopril) and aldosterone receptor antagonist (ARA) were used in early (10-12 month old), advanced (12-15 month old), and end (15-17 month old) stage of heart failure in Tgαq*44 mice. The systolic and diastolic functions of left ventricle were evaluated before and after therapy using magnetic resonance imaging (MRI). Additional dobutamine stress tests were performed for the assessment of cardiac reserve in the end - stage HF . The heart failure progression in Tgαq*44 mice was also assessed by morphometric parameters (ventricular weight), biochemical parameters (level of BNP, aldosterone). Based on parameters obtained from MRI and LV time – area curve following parameters of cardiac function were assessed: end-diastoli ; c area (EDA), end-systolic area (ESA), ejection ratio (ER), filling ratio (FR), fractional area change (FAC). In addition to the study on Tgαq*44 mice, the echocardiography examinations in short parasternal and long apical axis were also performed in patient with heart failure. The following parameters were assessed : EDA, ESA, FAC, FR, ER. The results of all these animals studies indicated that ACE inhibition in Tgαq*44 mice was more effective in the advanced and end -stage of heart failure but not in early stage of this pathology. In particular ACE inhibitor monotherapy (perindopril) in advanced stage of heart failure, resulted the decrease in ESA and increase in FAC without influence on others LV parameters. Monotherapy with ARA (alodosterone) was more effective than combined therapy ACE inhibitor (perindopril) and ARA (aldosterone). In the end - stage of heart failure combined therapy essentially inhibited the dilatation of LV and progression of diastolic and systolic impairment, as compared with the control group. The echocardiography examinations (based on actual recommendations) of patients with systolic and diastolic dysfunction were also performed. The echocardiography examinations revealed that systolic and diastolic parameters in long axis and reflected the impairment of ER and FR which were estimated in short parasternal axis, indicating that systolic and diastolic ; parameters based on MRI are justified.
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farmakologia ; choroby układu krążenia
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Last modified:
Mar 16, 2023
In our library since:
Jun 15, 2015
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1
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http://dl.cm-uj.krakow.pl:8080/publication/3996
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| Edition name | Date |
|---|---|
| ZB-122739 | Mar 16, 2023 |
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