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Trandolapril decreases prevalence of ventricular ectopic activity in middle-aged SHR
B Chevalier1, D Heudes, C Heymes
1INSERM-U127, Hôpital Lariboisière, Paris, France.
Insights
Trandolapril treatment reduced ventricular arrhythmias in hypertensive rats by decreasing cardiac hypertrophy and fibrosis. This suggests ACE inhibitors can help manage arrhythmias linked to hypertensive heart disease.
Area of Science:
- Cardiology
- Pharmacology
- Hypertension Research
Background:
- Hypertensive heart disease is linked to severe arrhythmias.
- The relationship between ventricular remodeling and arrhythmias in hypertension is not well understood.
Purpose of the Study:
- To investigate the effect of trandolapril on ventricular arrhythmias and cardiac remodeling in spontaneously hypertensive rats.
- To explore the correlation between cardiac structural modifications and ectopic activity.
Main Methods:
- Holter monitoring and morphometric analysis were used in spontaneously hypertensive rats and Wistar rats.
- Treatment involved trandolapril (an ACE inhibitor) for 3 months.
- Statistical analysis included simple regression and multivariate data analysis.
Main Results:
- Spontaneously hypertensive rats exhibited higher cardiac mass, fibrosis, and ventricular premature beats (VPB) with decreased heart rate.
- Trandolapril treatment significantly reduced cardiac hypertrophy, fibrosis, and VPB incidence in these rats.
- VPB incidence strongly correlated with severe hypertrophy and fibrosis.
Conclusions:
- Trandolapril treatment effectively regresses ventricular premature beats in hypertensive rats.
- Regression of VPB is linked to reduced hypertrophy and fibrosis, with other factors like myocardial phenotype and calcium metabolism also involved.
- The study presents a useful model for correlating myocardial structural changes with ectopic activity.
Background:
Although severe arrhythmias are still a major problem in patients with left ventricular hypertrophy (LVH), the relationship between ventricular remodeling and its regression or prevention, and the prevalence of ventricular premature beats (VPB) or more sustained arrhythmias are still poorly explored in hypertensive heart disease.
Methods And Results:
Holter monitoring was used to quantify supraventricular premature beats and VPB and heart rate (HR) in middle-aged spontaneously hypertensive rats (SHR) and Wistar rats treated for 3 months with trandolapril (ACE inhibitor, 0.3 mg/kg per day). Hypertrophy and fibrosis were morphometrically determined. Statistical analysis was performed with the use of simple regression and multivariate data analysis (cluster and correspondence analysis). SHR have higher cardiac mass and fibrosis, more VPB, and a decreased HR. Cluster analysis demonstrated that trandolapril was only effective in SHR. Trandolapril significantly reduced cardiac hypertrophy, fibrosis, and VPB incidence and increased the HR. Simple regression analysis showed that VPB incidence correlated to both hypertrophy and fibrosis. Correspondence analysis evidenced a strong correlation between hypertrophy, fibrosis, and VPB, but only for severe hypertrophy, and the correlation disappeared for moderate hypertrophy.
Conclusions:
After trandolapril treatment, the regression of VPB incidence not only is linked to hypertrophy and fibrosis, but additional causal factors also are involved including the myocardial phenotype and new calcium metabolism. Our model of Holter monitoring in conscious middle-aged SHR and multivariate data analysis might be useful in correlating myocardial structural modifications and ectopic activity.