M. Pagani

Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog.

In 57 normal subjects (age 20–60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90° upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) β-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at ∼0.25 Hz and a low frequency at ∼0.1 Hz, with a normalized low frequency: high frequency ratio of 3.6 ± 0.7. With tilt, the low-frequency component became largely predominant (90 ± 1%) withalow frequency: high frequency ratio of 21 ± 4. Acute β-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency: high frequency ratio induced by tilt. Chronic β-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency: high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency: high frequency ratio (0.7 ± 0.1); during tilt, the increase in the low frequency: high frequency ratio (8.3 ± 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency: high frequency ratio at rest of 2.8 ± 0.7, which became 17 ± 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation. Bilateral stellectomy prevented this low-frequency increase in R-R but not in arterial pressure autospectra, indicating that sympathetic nerves to the heart are instrumental in the genesis of low-frequency oscillations in R-R interval.

Changes in autonomic regulation induced by physical training in mild hypertension.

The adaptive effects of physical training on cardiovascular control mechanisms were studied in 11 subjects with mild hypertension. In these subjects we assessed the gain of the heart periodsystolic arterial pressure relationship in the unfit and the fit state by using 1) an open loop approach, whereby the gain is expressed by the slope of the regression of heart period as a function of systolic arterial pressure, during a phenylephrine-induced pressure rise and 2) a closed loop approach with proper simplification, whereby the gain is expressed by the index a, obtained through simultaneous spectral analysis of the spontaneous variabilities of heart period and systolic arterial pressure. Both methods indicated that training significantly increased the gain of the relationship between heart period and systolk arterial pressure at rest and reduced arterial pressure and increased heart period significantly. This gam was drastically reduced during bicycle exercise both in the unfit and fit state. In a second group of normotensive (n = 7; systolic pressure, 133 ± 3 mm Hg) and hypertensive (n = 7; systolic pressure, 180 ± 10 mm Hg) subjects undergoing 24 -hour diagnostic continuous ekctrocardiographic and high fidelity arterial pressure monitoring, the index a was significantly reduced in the hypertensive group at rest. Furthermore, when analyzed continuously over the entire 24-hour period, this index underwentminute-to-minute changes with lower values during the day and higher values during the night. We propose the index a as a quantitative indicator of the changes in the gain of baroreceptor mechanisms occurring with physical training in mild hypertension and during a 24-hour period in ambulatory subjects.

Spectral and cross-spectral analysis of heart rate and arterial blood pressure variability signals

A parametric method for autoregressive (AR) auto- and cross-spectral analysis is presented for the contemporaneous processing of heart rate and arterial blood pressure variability signals. In particular, the introduced bivariate spectral analysis (phase and coherence spectra) provides quantitative and objective means which are useful to measure the role played by the neural controlling systems (sympathetic and parasympathetic systems) on the cardiovascular signals under different pathophysiological conditions. Algorithmic aspects, connected to the way of processing discrete numerical series synchronized to single cardiac beats, are particularly stressed. Important applications are foreseen both in physiological studies and in clinical practice as an aid to the detection of various relevant cardiovascular pathologies such as hypertension and diabetes.

Cardiovascular variability signals: towards the identification of a closed-loop model of the neural control mechanisms

The authors consider parametric methods for processing cardiovascular signals and try to provide a global, although indirect evaluation of some neural regulatory activities. In particular, the variability signals of the heart rate (under the form of interval tachogram) and arterial blood pressure (systogram) together with respiratory movement signal (respirogram) are considered as inputs to a closed-loop model which describes a few aspects of the physiological interactions among the signals themselves. The identifiability of the transfer function of the model is demonstrated from the joint process black-box description of the signals. A direct identification procedure is proposed dividing the system into two dynamic adjustment models. A few suggestions are deduced on how and where the respirogram enters the model and on the genesis of the 10-s rhythm, parameters relevant to the Starling effect, Windkessel model, and the gain of baroreceptor mechanisms. The approach presented is intended also to provide a general frame for closed-loop identification in different pathophysiological conditions.<<ETX>>

Heart rate variability signal processing: A quantitative approach as an aid to diagnosis in cardiovascular pathologies

The heart rate variability (HRV) signal carries important information about the systems controlling heat rate and blood pressure, mainly elicited by autonomic nervous system (sympathetic and parasympathetic) controls. The present paper illustrates methods of HRV signal processing by using autoregressive (AR) modeling and power spectral density estimate. The information enhanced in this way seems to be particularly sensitive in discriminating various cardiovascular pathologies (hypertension, myocardial infarction, diabetic neuropathy, etc.). This method provides a simple non-invasive analysis, based on the processing of spontaneous oscillations in heart rate. Particular emphasis is directed to the algorithms used and to their direct application by using proper computerized techniques: only a few paradigmatical examples will be illustrated as preliminary results.

Model for the assessment of heart period and arterial pressure variability interactions and of respiration influences

A model which assesses the closed-loop interaction between heart period (HP) and arterial pressure (AP) variabilities and the influence of respiration on both is applied to evaluate the sources of low frequency (LF∼0·1 Hz) and high frequency (HF, respiratory rate ∼0·25 Hz) in conscious dogs (n=18) and humans (n=5). A resonance of AP closed-loop regulation is found to amplify LF oscillations. In dogs, the resonance gain increases slightly during baroreceptor unloading (mild hypotension obtained with nitroglycerine (NTG) i.v. infusion, n=8) and coronary artery occlusion ((CAO), n=6), and it is abolished by ganglionic transmission blockade ((ARF), Arfonad i.v. infusion, n=3). In humans, this gain is considerably increased by passive tilt. Different, possibly central, sources of LF oscillations are also evaluated, finding a strong rhythmic modulation of HP during CAO. At HF, a direct respiratory arrhythmia is dominant in dogs at control, while it is considerably reduced during CAO. On the contrary, in humans, a strong influence of respiration on AP is shown which induces a reflex respiratory arrhythmia. An index of the gain of baroreceptive response, αcl, was decreased by NTG and CAO, and virtually abolished by chronic arterial baroreceptive denervation (TABD, n=4) and ARF.

Information domain analysis of cardiovascular variability signals: evaluation of regularity, synchronisation and co-ordination.

A unifying general approach to measure regularity, synchronisation and co-ordination is proposed. This approach is based on conditional entropy and is specifically designed to deal with a small amount of data (a few hundred samples). Quantitative and reliable indexes of regularity, synchronisation and co-ordination (ranging from 0 to 1) are derived in a domain (i.e. the information domain) different from time and frequency domains. The method is applied to evaluate regularity, synchronisation and co-ordination among cardiovascular beat-to-beat variability signals during sympathetic activation induced by head-up tilt (T), during the perturbing action produced by controlled respiration at 10, 15 and 20 breaths/min (CR10, CR15 and CR20), and after peripheral muscarinic blockade provoked by the administration of low and high doses of atropine (LD and HD). It is found that: (1) regularity of the RR interval series is around 0.209; (2) this increases during T, CR10 and HD; (3) the systolic arterial pressure (SAP) series is more regular (0.406) and its regularity is not affected by the specified experimental conditions; (4) the muscle sympathetic (MS) series is a complex signal (0.093) and its regularity is not influenced by HD and LD; (5) the RR interval and SAP series are significantly, though weakly, synchronised (0.093) and their coupling increases during T, CR10 and CR15; (6) the RR interval and respiration are coupled (0.152) and their coupling increases during CR10; (7) SAP and respiration are significantly synchronised (0.108) and synchronisation increases during CR10; (8) MS and respiration are uncoupled and become coupled (0.119) after HD; (9) the RR interval, SAP and respiration are significantly co-ordinated (0.118) and co-ordination increases during CR10 and CR15; (10) during HD the co-ordination among SAP, MS and the respiratory signal is larger than that among the RR interval, SAP, MS and the respiratory signal, thus indicating that the RR interval contributes towards reducing co-ordination.

Altered pattern of circadian neural control of heart period in mild hypertension.

We addressed the problem of the circadian changes in neural control of heart period in ambulant hypertensive subjects. A running spectral analysis of R-R variability from Holter tapes provided markers of sympathetic, i.e. low-frequency component (LF) almost equal to 0.10 Hz, and vagal, i.e. high-frequency component (HF) almost equal to 0.25 Hz, controlling activities for the 24-h period of the recording. Significant circadian differences were observed in LF between the two groups of subjects: during night-time rest (0300-0400 h), LF was greater in hypertensives than in normotensives (56 +/- 2 and 48 +/- 2 nu, respectively; P less than 0.05). Furthermore, the difference between daytime and night-time LF values was progressively reduced with increasing severity of the hypertensive state, as assessed by resting arterial pressure levels. Spectral analysis of R-R variability suggests that essential hypertension may be characterized by a reduced day-night oscillation in sympathetic activity than can be quantified non-invasively using this approach.

A positive feedback sympathetic pressor reflex during stretch of the thoracic aorta in conscious dogs.

The role of pressor sympathetic reflexes in circulatory control was investigated in conscious dogs. Animals were previously instrumented with a 6- to 8-cm rigid core cannula covered by an inflatable rubber cylinder in the thoracic aorta, a pressure catheter implanted in the aorta above the cannula, and a second catheter inserted into the aorta below the cannula through a femoral artery. Two piezoelectric crystals were positioned at opposing adventitial sites to measure aortic distension with ultrasound techniques. After recovery from surgery, the diameter of the aortic segment surrounding the cannula was increased by 9.6 ± 0.4% from 16 ± 1 mm by inflating the rubber cylinder, without obstructing blood flow. Mean aortic pressure rose 31 ± 3% from 100 ± 3 mm Hg and heart rate 20 ± 3% from 91 ± 3 beats/min (P < 0.01). The pressor response was abolished by α-adrenergic blockade (phentolamine 1 mg/kg, iv). The heart rate response was reduced either by β-blockade (propranolol 1 mg/kg, iv) or muscarinic blockade (atropine 0.2 mg/kg, iv) and abolished by their combination. During aortic stretch, the sensitivity of the baroreflex was reduced 57 ± 7% from 18 ± 2 msec/mm Hg (P < 0.01). The pressor response was increased to 49 ± 8% after bilateral carotid sinus nerve section and vagotomy. These excitatory reflex responses were obtained in absence of any pain reaction. Thus, in the conscious dog, aortic distension within physiological ranges induces a potent pressor sympathetic reflex with positive feedback characteristics. Such a pressor reflex not only occurs in the presence of functioning baroreflexes, but is also capable of reducing their sensitivity.

Contrasting effects of acute and chronic cigarette smoking on skin microcirculation in young healthy subjects.

Objective The aim of our study was to assess the effects of acute and chronic smoking on skin microvascular properties of young healthy subjects. Design An observational study, using a totally non-invasive approach, employing continuous palmar microvascular flow (laser Doppler) and arterial pressure measurements, to compute estimates of microvascular resistive (Z0) and oscillatory (impedance, i.e. ZC) properties. Measures were obtained at baseline and after iontophoretic administration of acetylcholine (ACh), an endothelium-dependent vasodilator and of sodium nitroprusside (NP), an endothelium-independent vasodilator. Participants A total of 20 healthy male subjects (nine habitual smokers and 11 non-smokers; aged 27 ± 1 and 29 ± 2 years, respectively) in resting conditions and during administration of ACh and of NP (in two different days), before and after smoking one cigarette were evaluated. Results Smokers showed significant lower baseline Z0 and ZC than non-smokers. In non-smokers, ACh and NP iontophoresis induced a significant decrease of both Z0 and ZC, before and after smoking one cigarette (P < 0.02). Conversely, in smokers, both Z0 and ZC were not affected by ACh iontophoresis before acute smoking, while, after smoking, a significant decrease of both Z0 and ZC (P < 0.02) was detected after ACh challenge. In smokers, both Z0 and ZC were not affected by NP iontophoresis, either before or after smoking a cigarette. Conclusions Smokers appeared characterized by a complex disruption of peripheral microcirculatory regulation, including inappropriate resting vasodilation, impaired endothelium-dependent and independent vasodilation, paradoxical recovery of endothelium-dependent vasodilation in response to acute smoking.