title: Heart rate and heart rate variability, a pharmacological target.
abstract: Heart rate varies with respiration, blood pressure, emotion, etc., and heart rate variability (HRV) is presently one of the best indices to predict fatal issues in cardiac failure and after myocardial infarction. HRV depends on various reflexes. In addition, parallel studies of HRV and the myocardial adrenergic and muscarinic transduction system in experimental models of cardiac hypertrophy (CH) have suggested that the myocardial phenotype at the sinus-node level may also play a role. A transgenic strain of mice with atrial overexpression of the beta 1-adrenergic receptors was generated with attenuated HRV, which demonstrates that the phenotype itself is a determinant of HRV. HRV is explored by noninvasive techniques, including simple determination of the standard error of the mean, time-domain analysis, and Fourier transformation. We recently developed a time and frequency domain method of analysis, the smoothed pseudo-Wigner-Ville transformation, which allows better exploration of nonstationarity. Nonlinear methods have also been applied due to the extreme complexity of the biological determinants, and have provided evidence of a chaotic attractor in certain conditions. It is proposed that in steady state a very simple process, which is not completely deterministic, could better explain intermit interval regulations than chaotic behavior. In contrast, under extreme circumstances the regulation proceeds using chaotic behavior. Arrhythmias and HRV can be quantitated in 16-month-old unanesthetized spontaneously hypertensive rats (SHR). Ventricular premature beats are more frequent in SHR than in age-matched controls; they disappear after converting enzyme inhibition (CEI) relative to the reduction of both cardiac hypertrophy and ventricular fibrosis. HRV is attenuated in SHR, as it is in compensatory CH in humans. When CH is prevented, HRV returns to normal. CEI is therefore antiarrhythmic. Another pharmacological application of this concept concerns the bradycardic agents that may improve HRV.
authors.affiliation: U 127-INSERM, IFR Circulation, Hopital Lariboisière, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Swynghedauw
authors.forename: S
authors.initials: S
authors.lastname: Jasson
authors.forename: B
authors.initials: B
authors.lastname: Chevalier
authors.forename: J
authors.initials: J
authors.lastname: Clairambault
authors.forename: S
authors.initials: S
authors.lastname: Hardouin
authors.forename: C
authors.initials: C
authors.lastname: Heymes
authors.forename: L
authors.initials: L
authors.lastname: Mangin
authors.forename: P
authors.initials: P
authors.lastname: Mansier
authors.forename: C
authors.initials: C
authors.lastname: Médigue
authors.forename: J M
authors.initials: JM
authors.lastname: Moalic
authors.forename: N
authors.initials: N
authors.lastname: Thibault
authors.forename: F
authors.initials: F
authors.lastname: Carré
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D002303:Cardiac Output, Low / Q000188:drug therapy*; D003627:Data Interpretation, Statistical; D005583:Fourier Analysis; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D010641:Phenotype; D011379:Prognosis