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Long acting calcium antagonist amlodipine prevents left ventricular remodeling after myocardial infarction in rats
T Shimada1, M Yoshiyama, K Takeuchi
1First Department of Internal Medicine, Osaka City University Medical School, Japan.
Insights
Amlodipine treatment effectively prevents adverse left ventricular remodeling and dysfunction following myocardial infarction in rats. It also inhibits abnormal cardiac gene expression, preserving heart function.
Area of Science:
- Cardiovascular Pharmacology
- Molecular Cardiology
- Translational Medicine
Background:
- Myocardial infarction (MI) often leads to detrimental left ventricular remodeling, characterized by systolic and diastolic dysfunction.
- Abnormal cardiac gene expression is a key feature of post-MI remodeling, contributing to disease progression.
Purpose of the Study:
- To investigate the therapeutic effects of amlodipine, a calcium channel blocker, on left ventricular remodeling and cardiac gene expression in a rat model of myocardial infarction.
Main Methods:
- Rats underwent myocardial infarction and were randomized to receive amlodipine or serve as untreated controls.
- Echocardiography and hemodynamic measurements were performed at four weeks post-MI.
- Cardiac mRNA levels of specific genes were analyzed in ventricular tissues.
Main Results:
- Amlodipine significantly reduced elevated left ventricular end-diastolic pressure and central venous pressure.
- The drug attenuated right ventricular hypertrophy and prevented left ventricular dilation.
- Amlodipine improved fractional shortening (systolic function) and normalized E wave deceleration rate (diastolic function).
- Treatment suppressed the upregulation of beta-myosin heavy chain (MHC), alpha-skeletal actin, and atrial natriuretic peptide (ANP) mRNAs, while restoring alpha-MHC levels.
Conclusions:
- Amlodipine effectively prevents adverse left ventricular remodeling and associated systolic and diastolic dysfunction post-myocardial infarction.
- The drug inhibits abnormal cardiac gene expression changes, offering a protective effect on the infarcted heart.
Objective:
The purpose of this study was to examine the effect of amlodipine, a long-acting calcium antagonist, on the left ventricular remodeling, including systolic and diastolic dysfunction, the change of cardiac gene expression in the myocardial infarcted rats (MI).
Methods:
On the first day after myocardial infarction, the animals were randomly assigned to amlodipine treatment (n = 8) or untreated groups (MI; n = 9). We then performed Doppler-echocardiographic examinations and measured the hemodynamics at four weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed.
Results:
Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 22 +/- 1 mmHg and 5 +/- 1 mmHg. Amlodipine reduced LVEDP and CVP to 15 +/- 1 mmHg (P < 0.01) and 3 +/- 0 mmHg (P < 0.01). The weight of right ventricle in MI was significantly larger than in the control rats (Control; 0.48 +/- 0.01 g/kg, MI; 0.79 +/- 0.04 g/kg, P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3 mm (P < 0.01) (Control; 6.2 +/- 0.3 mm). Amlodipine prevented an increase of the weight of right ventricle (0.62 +/- 0.03 g/kg, P < 0.01) and LVDd (7.9 +/- 0.2 mm, P < 0.01 to MI). The rats in MI showed systolic dysfunction shown by the decreased fractional shortening (Control; 31 +/- 2% versus MI; 15 +/- 1%, P < 0.01), and diastolic dysfunction shown by E wave deceleration rate (Control; 18.1 +/- 2.0 m/s2, MI; 32.6 +/- 2.1 m/s2, P < 0.01). Amlodipine significantly prevented systolic and diastolic dysfunction. The increases in beta-MHC, alpha-skeletal actin, and ANP mRNAs in the non-infarcted left ventricle and right ventricle at four weeks after the myocardial infarction were all significantly suppressed by the treatment with amlodipine. On the other hand, depressed alpha-MHC was restored to normal levels by amlodipine in both regions.
Conclusions:
Amlodipine prevents the left ventricular remodeling process accompanied by systolic and diastolic dysfunction, and inhibits abnormal cardiac gene expression after myocardial infarction.