Relation of mean heart rate and heart rate variability in patients with left ventricular dysfunction.

The new finding was that mean heart rate and heart rate variability were more closely coupled in patients with more advanced LV dysfunction. Mean heart rate explained a larger portion of variance in heart rate variability in patients in the lowest LVEF quartile than in those in the highest one. These results support our hypothesis that sympathetic activation in patients with more severe LV dysfunction results in closer correlation between heart rate and heart rate variability. Generally, the correlation between mean heart rate and heart rate variability is weak because heart rate and heart rate variability represent different modalities of cardiovascular regulation. Mean heart rate is normally determined by the interactions of both the sympathetic and parasympathetic nervous systems, whereas modulation of these activities, with different gains, determines the magnitude of heart rate variability. This results in great complexity in control of the heart by the autonomic nervous system. However, heart rate is likely to be more dominantly regulated by the sympathetic nervous system because of vagal withdrawal in patients with more severe LV dysfunction. The effect of sympathetic cardiac modulation has been shown to be more sluggish than that of the parasympathetic nervous system in beat-to-beat regulation of heart rate. This may result in more blunted heart rate variability concomitantly with elevated mean heart rate. Thus, variation in heart rate variability in any given mean heart rate is likely to be lower than in patients with more preserved LV function, and hence with more complex cardiac autonomic regulation with involvement of the parasympathetic nervous system. Indeed, even the slopes of regression lines between mean heart rate and heart rate variability were similar in the first and fourth LVEF quartile; the intercept of the regression line was significantly higher in the fourth quartile than in the first one. This further supports our hypothesis.

The high frequency component of heart rate variability reflects cardiac parasympathetic modulation rather than parasympathetic 'tone'.

This study was designed to evaluate the effect of modulating cardiac parasympathetic input on the high frequency component of heart rate variability. We stimulated the right vagus nerve with three different stimulation patterns in anaesthetized, vagotomized and spinal anaesthetized dogs. We kept the mean stimulation frequency constant; controlled the amplitude of modulation with programmed stimulation patterns, and analysed the resulting heart rate variability by power spectral analysis. Constant frequency vagal stimulation increased the cardiac interval, but did not change heart rate variability markedly. There was a slight increase, from 11 +/- 2 to 27 +/- 11 ms2, in the high frequency component. However, when the instantaneous stimulation frequency oscillated between 4 and 17 Hz during 5 s period, we could produce a marked heart rate variation, with 91 +/- 9% of the variation corresponding to the frequency of the modulation (0.20 Hz). The high frequency component was 12932 +/- 7701 ms2. With an increased magnitude of modulation, i.e. the difference between minimum and maximum instantaneous frequency, the high frequency component increased to 32711 +/- 17943 ms2. Thus, the high frequency component of heart rate variability reflects the magnitude of fluctuation in the cardiac parasympathetic input rather than parasympathetic 'tone'.

Effect of sympathetic modulation and sympatho-vagal interaction on heart rate variability in anaesthetized dogs.

Changes in the function of the autonomic nervous system underlying changes in heart rate variability are not fully understood. Furthermore, decreased heart rate variability has been found to be related to poor prognosis, for example, in patients with coronary artery disease. Our aim was to study how modulation in sympathetic stimulation at various frequencies is transferred into heart rate variation, and how the interaction between sympathetic and parasympathetic inputs can affect the high-frequency component of heart rate variability. We stimulated electrically cardiac sympathetic and vagal nerves in anaesthetized, vagotomized, spinal anaesthetized dogs. We controlled the frequency and magnitude of the modulation in programmed stimulation patterns and analysed the resulting changes in heart rate variability by power spectral analysis. We found that modulations in sympathetic stimulation were reflected in the high-frequency component of heart rate variability, as well as in the low- and medium-frequency components. In addition, a novel finding was that sympathetic stimulation reduced the magnitude of the high-frequency variations caused by vagal stimulation. This suggests that, although the high-frequency component of heart rate variability is mainly under parasympathetic regulation, it may also be influenced by the sympathetic nervous system.

Periodicity, amplitude and width of synchronized cardiac sympathetic nerve activity in anaesthetized cats.

Using a recently developed method, we studied periodicity, amplitude and width of synchronized cardiac sympathetic nerve activity (CSNA) at various intervals of periodic baroreceptor input in anaesthetized cats. ECG, aortic pressure and CSNA were recorded when cardiac interval was changed by artificial pacing, or when the aortic nerve was stimulated after baroreceptor denervation. The periodicity of synchronized CSNA showed mainly two modes: one was 8-14 Hz rhythmicity (Tc) and the other was related to cardiac cycle (Tb). The Tc mode was almost constant and independent of cardiac interval or stimulation. The probability of the Tc mode increased as pacing interval increased. The Tb mode reflected the interval of inhibition in CSNA due to pulsatile baroreceptor input. The mode of inhibitory rhythm (Ts) related to the stimulation of the aortic nerve was almost constant and independent of the stimulation interval. The probability of the Ts mode was highest at a 250-ms interval and decreased with increase in stimulus interval. The mean peak height or mean peak width did not changed significantly during pacing the heart at various intervals nor after baroreceptor denervation. The peak height and peak width had a significant linear relationship at any cardiac interval or after baroreceptor denervation, whereas no relationship between the peak-to-peak interval and the peak height or peak width was found. These results indicate that the cardiac-related rhythm is produced by inhibition of transmission of the fundamental rhythm by periodic baroreceptor input. Our results suggest also that the amplitude and periodicity of synchronized CSNA are separately regulated.

Origin of cardiac-related synchronized cardiac sympathetic nerve activity in anaesthetized cats.

To study the origin of cardiac-related rhythm in cardiac sympathetic nerve activity (CSNA), ECG, aortic pressure and CSNA were recorded when cardiac interval was changed by artificial pacing, or when the aortic nerve was stimulated after baroreceptor denervation in anaesthetized cats. CSNA was averaged by using the R-wave of ECG, or stimulus pulse as a trigger. Delay times from arterial pulse or stimulus pulse to the onset and half amplitude of inhibition and to the maximal inhibition were measured from the averaged data. The delay of inhibition in CSNA was constant and independent of pacing interval. Stimulation of the aortic nerve with single shocks caused an inhibition in averaged CSNA. The delay of inhibition was constant and independent of stimulus frequency. These results indicate that the cardiac-related rhythm in CSNA is produced reflexly by inhibiting the transmission of the fundamental rhythmicity due to periodic baroreceptor input.

Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs.

Short-term oscillation of heart rate and blood pressure are mainly regulated by the automatic nervous system. It has been proposed that non-neural factors, such as changes in intrathoracic pressure, can strongly modulate this rhythmicity. Our aim was to evaluate the effect of changing intrathoracic pressure and central autonomic nervous activity on heart rate and blood pressure variability. Evaluation was performed by using spectral analysis techniques with autoregressive modelling. The variability in heart rate and blood pressure remained in animals with open chest or paralysed respiratory muscles. After vagotomy, the variability in heart rate decreased, but not that of blood pressure. Total spinal anaesthesia elicited a decrease in the variability in blood pressure. The pharmacological blockade of alpha- and beta-receptors further decreased both variabilities. It was concluded that in anaesthetized dogs heart rate and blood pressure variability are mainly of central origin and non-neural factors have only minor effect on these central rhythms. High (> 0.15 Hz), medium (0.07-0.15 Hz) and, obviously low (0.00-0.07 Hz) frequency variations in heart rate are mostly mediated vagally. In blood pressure, medium and obviously low frequency variations are modulated by sympathetic nervous system, whereas high frequency variations are secondary to the heart rate variation.