Related Experiment Videos
Molecular basis of the regression of cardiac hypertrophy
B Swynghedauw1, B Chevalier, C Médigue
1U127-INSERM, Hospital Lariboisiére, Paris, France.
Insights
This study shows that treating spontaneously hypertensive rats with a CEI effectively lowers blood pressure, reduces heart muscle thickening and fibrosis, and improves heart rate variability. The treatment also suppresses abnormal heartbeats, indicating a potential benefit for cardiac failure.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Cardiac failure involves impaired myocardial adaptation, peripheral adaptation to low cardiac output, and fibrosis.
- Fibrosis, characterized by increased collagen concentration, is linked to aging, ischemia, and hormonal changes, not solely mechanical overload.
- Spontaneously hypertensive rats (SHRs) serve as a relevant model for studying clinical cardiac failure.
Purpose of the Study:
- To investigate the effects of a three-month treatment with a converting enzyme inhibitor (CEI) on cardiac function and structure in middle-aged SHRs.
- To assess the impact of CEI treatment on arterial hypertension, left ventricular hypertrophy, and ventricular fibrosis.
- To evaluate changes in cardiac rhythm and heart rate variability in response to CEI therapy.
Main Methods:
- Treatment of SHRs with a CEI for three months.
- Monitoring of arterial blood pressure, left ventricular hypertrophy, and ventricular fibrosis.
- Holter monitoring to assess ventricular premature beats.
- Quantification of heart rate variability using the pseudo Wigner-Villé transformation.
Main Results:
- CEI treatment significantly reduced arterial hypertension, left ventricular hypertrophy, and ventricular fibrosis in SHRs.
- Untreated SHRs exhibited an increased number of ventricular premature beats compared to Wistar rats, which were suppressed by CEI treatment.
- CEI therapy normalized low-frequency oscillations in heart rate variability, which were previously hampered in SHRs.
Conclusions:
- CEI treatment offers a multi-faceted benefit in a rat model of cardiac failure, addressing hypertension, cardiac remodeling, and arrhythmias.
- The findings suggest that CEI therapy can improve cardiac autonomic function by normalizing heart rate variability.
- CEI treatment demonstrates potential in mitigating key pathological mechanisms contributing to cardiac dysfunction in hypertensive individuals.
Abstract:
Cardiac failure is a disease which involves three different mechanisms: (1) the limits and imperfections of the general process of myocardial adaptation to mechanical stress, which includes various changes in genetic expression, including an increased collagen mass, but an unchanged collagen concentration; (2) the limits and imperfections of the adaptational process at the peripheral level which allows the entire organism to adapt to the low cardiac output; (3) fibrosis, an augmented collagen concentration, which is not a direct consequence of mechanical overload, but depends on aging, myocardial ischemia or hormonal changes. Middle-aged spontaneously hypertensive rats (SHRs) represent a good model of the common clinical situation. Three-month treatment with a CEI reduces, in parallel, arterial hypertension, left ventricular hypertrophy and ventricular fibrosis. Holter monitoring was also performed in these animals. Untreated SHRs when compared to age-matched Wistar rats have an increased number of ventricular premature beats which are suppressed by the treatment. In addition, heart rate variability has been quantified by using the pseudo Wigner-Villé transformation, a time and frequency domain method. The low frequency oscillations are hampered in SHRs. CEI normalizes this parameter.