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Title: The therapeutic efficacy of the renin–angiotensin–aldosterone system inhibition on myocardial function in amurine model of dilated cardiomyopathy (Tgq*44 mice)


The Tgq*44 mice exhibit a unique animal model of HF inwhich the overexpression of active q subunit of the Gprotein in cardiomyocytes mimic persistent receptor(adrenergic 1,angiotensin AT1, endothelin ET-A)stimulates and activates the intracellular signal pathways.These intracellular pathways are known to play key roles inthe pathogenesis of the heart hypertrophy and cause heartfailure in humans.The purpose of this study was to assess the effect of twomonth therapy with angiotensin-converting enzyme inhibitor(ACE-I) and aldosterone receptor antagonist (ARA) on leftventricle functions in Tgq *44 mice. In the course of thisstudy, the ACE inhibitor (perindopril) and aldosteronereceptor antagonist (ARA) were used in early (10-12 monthold), advanced (12-15 month old), and end (15-17 monthold) stage of heart failure in Tgq*44 mice. The systolic anddiastolic functions of left ventricle were evaluated beforeand after therapy using magnetic resonance imaging (MRI).Additional dobutamine stress tests were performed for theassessment of cardiac reserve in the end - stage HF .The heart failure progression in Tgq*44 mice was alsoassessed by morphometric parameters (ventricular weight),biochemical parameters (level of BNP, aldosterone). Basedon parameters obtained from MRI and LV time - areacurve following parameters of cardiac function wereassessed: end-diastolic area (EDA), end-systolic area (ESA),ejection ratio (ER), filling ratio (FR), fractional area change(FAC).In addition to the study on Tgaq*44 mice, theechocardiography examinations in short parasternal and longapical 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 indicatedthat ACE inhibition in Tgq*44 mice was more effective inthe advanced and end -stage of heart failure but not in earlystage of this pathology. In particular ACE inhibitormonotherapy (perindopril) in advanced stage of heartfailure, resulted the decrease in ESA and increase in FACwithout influence on others LV parameters. Monotherapywith ARA (alodosterone) was more effective thancombined therapy ACE inhibitor (perindopril) and ARA(aldosterone). In the end - stage of heart failure combinedtherapy essentially inhibited the dilatation of LV andprogression of diastolic and systolic impairment, ascompared with the control group.The echocardiography examinations (based on actualrecommendations) of patients with systolic and diastolicdysfunction were also performed. The echocardiographyexaminations revealed that systolic and diastolic parametersin long axis and reflected the impairment of ER and FRwhich were estimated in short parasternal axis, indicatingthat systolic and diastolic parameters based on MRI arejustified.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

farmakologia ; choroby układu krążenia

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Lekarski.


Stefan Chłopicki

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tylko w bibliotece

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Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

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Last modified:

May 24, 2021

In our library since:

Jun 15, 2015

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Edition name Date
ZB-122739 May 24, 2021


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