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Myocardial determinants in regulation of the heart rate
B Swynghedauw1, S Jasson, J Clairambault
1U 127-INSERM-Hopital Lariboisiére, Paris, France.
Insights
Reduced heart rate variability (HRV) is a key prognostic factor in cardiac conditions. This study developed a new method to analyze HRV and arrhythmias in rodents, finding that converting enzyme inhibition improves outcomes by preventing arrhythmias.
Area of Science:
- Cardiology
- Physiology
- Biomedical Engineering
Background:
- Reduced heart rate variability (HRV) is a critical prognostic indicator following myocardial infarction and in cardiac insufficiency.
- HRV analysis, typically using spectral analysis, faces limitations with unstable heart rates in small rodents.
- Nonlinear methods and the Wigner-Villé Transform offer alternatives for HRV analysis in diverse species.
Purpose of the Study:
- To develop and validate a novel method for quantifying arrhythmias and HRV in unanesthetized rodents.
- To investigate the relationship between physiological parameters, myocardial phenotype, and HRV.
- To assess the impact of converting enzyme inhibition on arrhythmias, HRV, and cardiac remodeling.
Main Methods:
- Development of a new method to quantify arrhythmias and HRV in unanesthetized rodents.
- Utilized spontaneously hypertensive rats and age-matched controls for comparative analysis.
- Assessed the effects of converting enzyme inhibition on arterial hypertension, cardiac hypertrophy, fibrosis, ventricular premature beats, and HRV.
Main Results:
- Spontaneously hypertensive rats exhibit more frequent ventricular premature beats and attenuated HRV compared to controls.
- Ventricular premature beat incidence is independently linked to cardiac hypertrophy and fibrosis.
- Converting enzyme inhibition concurrently reduced hypertension, hypertrophy, fibrosis, prevented premature beats, and normalized HRV.
Conclusions:
- The developed method enables robust quantification of arrhythmias and HRV in rodents, facilitating studies on cardiac health.
- Attenuated HRV and increased ventricular premature beats in hypertensive rats reflect a detrimental myocardial phenotype.
- Converting enzyme inhibition demonstrates significant cardioprotective effects by mitigating arrhythmias and improving HRV, highlighting its therapeutic potential.
Abstract:
Heart rate is a function of at least three factors located in the sinus node, including the pacemaker and the activity of the sympathetic and vagal pathways. Heart rate varies during breathing and exercising. The is far from being a purely academic question because, after myocardial infarction or in cardiac insufficiency, reduced heart rate variability (HRV) represents the most valuable prognostic factor. HRV is usually considered index of the sympathovagal balance and is explored using time domain analysis, such as spectral analysis. Nevertheless, methods such as the Fast Fourier Transformation are not applicable to small rodents which have an unstable heart rate with asymmetric oscillations. Nonlinear methods show chaotic behavior under some conditions. A time and frequency domain method of analysis, the Wigner-Villé Transform, has been proposed for the study of HRV in both humans and small rodents, as a compromise between linear and nonlinear methods. We developed a method to quantify both arrhythmias and HRV in unanesthetized rodents. Such a method allows study of the relationship between the physiological parameters and the myocardial phenotype. Ventricular premature beats are more frequent in 16-month-old spontaneously hypertensive rats than in age-matched controls. In addition, HRV is attenuated in spontaneously hypertensive rats, as in compensatory cardiac hypertrophy in humans, and such attenuation is considered a prognostic index. Converting enzyme inhibition reduces in parallel arterial hypertension, cardiac hypertrophy, and ventricular fibrosis; it prevents ventricular premature beats and normalizes heart rate variability. It can be demonstrated that the incidence of ventricular premature beats is linked to the myocardial phenotype in terms of both cardiac hypertrophy and fibrosis. The two factors act as independent variables. HRV is correlated with the incidence of arrhythmias, suggesting that the beneficial effects of converting enzyme inhibition are related to prevention of arrhythmias.