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In this study, we used spectral analysis of short-term R-R and systolic arterial pressure (SAP) variabilities to estimate the changes in neural control of the circulation produced by psychological stress. The 0.1 Hz low-frequency (LF) component of R-R and SAP variabilities provided a quantitative index of the sympathetic activity controlling heart rate and vasomotion. Conversely the high-frequency (HF) respiratory component of R-R variability provided an index of vagal tone. In conscious dogs we used the seemingly stressful situation of being accompanied for the first time to the experimental laboratory as a stimulus. In human subjects we used mental arithmetic. In both cases LF of R-R and SAP variabilities increased significantly suggesting enhanced sympathetic activity both to the SA node and the vasculature. In man, the index alpha, a measure of the overall gain of baroreceptor mechanisms, was found to be reduced during mental arithmetic. Spectral analysis of cardiovascular variabilities thus suggests that in man and in conscious dogs psychological challenges induce a profound re-arrangement of neural control of the circulation, which appears to be characterised by sympathetic predominance and which can be monitored by this technique.

A duplication of the sub-bands 1q42.11 and 1q42.12 was found in a boy and his mother. The proband has short stature (around the 10th centile) but a normal phenotype and psychomotor development. His mother is also asymptomatic. We found 30 published cases of normal subjects with an imbalance of autosomal euchromatic material. In these cases the imbalance involved either only one G positive band or a G positive and a G negative band. Thus the absence of a phenotypic effect cannot always be ascribed to the deficiency in the G positive bands of coding DNA. Moreover, in some cases, the method of transmission of the chromosome abnormality was such that an imprinting effect could be postulated.

In this study, we tested the hypothesis that the neural control of circulation in humans undergoes continuous but in part predictable changes throughout the day and night. Dynamic 24-hour recordings were obtained in two groups of ambulant subjects. In 18 hospitalized patients free to move, direct high-fidelity arterial pressures and electrocardiograms were recorded, and in an additional 28 nonhospitalized subjects, only electrocardiograms were obtained. Spectral analysis of systolic arterial pressure and of RR interval variabilities provided quantitative markers of sympathetic and vagal control of the sinus node and of sympathetic modulation of vasomotor tone. With this approach, the low-frequency (approximately 0.1 Hz) component of RR interval and systolic arterial pressure variabilities is considered a marker primarily of sympathetic activity, whereas the high-frequency (approximately 0.25 Hz) component of RR interval variability, related to respiration, seems to be a marker primarily of vagal activity. We observed a pronounced and consistent reduction in the markers of sympathetic activity and an increase in those of vagal activity during the night. In the invasive studies, while the subjects were still lying in bed after waking up, the markers of sympathetic activity rose rapidly and concomitantly with a simultaneous vagal withdrawal. Noninvasive studies confirmed the early morning rise of the markers of sympathetic activity and the circadian pattern of sympathovagal balance. These data indicate that the ominously increased rate of cardiovascular events in the morning hours may reflect the sudden rise of sympathetic activity and the reduction of vagal tone.

In this paper the experimental evidence supporting the hypothesis that excitatory sympathetic reflexes may participate in the tonic control of the cardiovascular system is discussed. Positive feedback pressor sympathetic reflexes can be obtained with physiological distensions of the descending thoracic aorta in conscious dogs with all nerves intact in absence of any pain reaction. These excitatory reflexes interact with supraspinal regulatory mechanisms, inhibitory in nature. A massive excitation of cardiac sympathetic afferents, produced by intracoronary injections of bradykinin, also elicits a pressor reflex, without pain reactions. In the absence of anesthesia and recent surgery, the cardiovascular excitatory reflexes, subserved by sympathetic afferent fibers, can easily prevail. We suggest that negative and positive feedback mechanisms interact continuously to achieve the most adequate neural cardiovascular control.

The cardiac systolic and diastolic effects of the two major calcium blockers, verapamil and nifedipine, were studied and compared with those produced by dilazep, a relatively new vasodilator with calcium blocking properties, in conscious instrumented dogs to avoid the complications of anaesthesia and recent surgery. Mean arterial pressure was reduced by nifedipine and dilazep but not by verapamil, whereas peak left ventricular pressure was reduced only by dilazep and verapamil. Consistent tachycardia occurred, the rate being highest with nifedipine and lowest with dilazep. Left ventricular dP/dt was unaffected by dilazep, reduced by verapamil, and increased by nifedipine; this increase was no longer observed after beta adrenergic blockade. Ventricular relaxation was assessed by calculating the time relaxation constant, tau. Verapamil increased tau significantly only after beta adrenergic blockade, whereas nifedipine and dilazep reduced it both before and after beta adrenergic blockade. These data suggest that reflex beta adrenergic mechanisms may modulate the effects of calcium blockade on both systolic and diastolic performance.

1. The aim of the present experiment was to study in conscious animals the effect of chemical stimulation of cardiac sensory innervation by bradykinin, a physiological substance known to activate both vagal and sympathetic cardiac sensory nerve endings, at doses devoid of systemic haemodynamic effects. 2. In conscious dogs with implanted catheters bradykinin (100 ng/kg) injected into a cannulated branch of the left coronary artery induced significant (P less than 0.01, n = 5) reflex increases in mean arterial pressure and heart rate as well as increases in left ventricular pressure, left ventricular dP/dt max. and coronary blood flow. 3. These changes were obtained in the absence of pain reactions. 4. The concept, derived from experiments on anaesthetized animals, that chemical stimulation of the intact sensory supply of the heart always elicits a cardiovascular depressor reflex mediated by cardiac vagal afferents has to be modified, as pressor sympathetic reflexes may occur after an appropriate stimulus to the fully innervated heart of conscious dogs.

A system providing high quality direct arterial blood pressure recordings and electrocardiograms in ambulatory patients was devised using a modified commercially available Holter type magnetic tape recorder together with a microminiature Millar (3F) tip transducer. This system did not require a perfusion line and solved the major drawbacks of other available systems. Pressure and electrocardiographic data were fed directly from the playback unit into a minicomputer for automatic beat to beat waveform analysis. Thus the blood pressure and RR interval variability signals could be simultaneously analysed with autoregressive modelling techniques to provide a quantitative estimate of sympathovagal balance in ambulant patients. The system was reliable, simple, and safe to use.

In 10 ambulant subjects we studied the circadian changes in sympathetic vasomotor control as assessed by the spectral power of the 0.1-Hz low-frequency component of systolic arterial pressure variability measured with a Millar phi 3F tip transducer. The low-frequency component was higher during the daytime, while the subjects were performing light physical activity, and lower during the night, thus paralleling the circadian systolic blood pressure pattern. However, the morning low-frequency rise preceded the blood pressure increase by about 3 h, suggesting that vasometer control and blood pressure control are at least partly related to different mechanisms.

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 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-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 approximately 0.25 Hz and a low frequency at approximately 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%) with a low frequency:high frequency ratio of 21 +/- 4. Acute beta-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 beta-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.(ABSTRACT TRUNCATED AT 400 WORDS)

The reflex hemodynamic effects of intracoronary bradykinin were tested in 20 conscious instrumented dogs. When the experiments were performed after full recovery from surgery and anesthesia, graded doses (10-300 ng/kg) of bradykinin always produced graded pressor responses, in the absence of any pain reaction. At the maximum pressor response obtained with 100 ng/kg, mean arterial pressure rose 28 +/- 3% from 89 +/- 4 mm Hg, left ventricular pressure 20 +/- 3% from 121 +/- 2 mm Hg, heart rate 30 +/- 4% from 88 +/- 5 beats/min, rate of change of left ventricular pressure 18 +/- 3% from 2812 +/- 65 mm Hg/sec (P less than 0.01). Higher doses of bradykinin did not produce greater responses. The magnitude of the response was similar when the injection was performed in either the left anterior descending (change in mean arterial pressure 29 +/- 3%) or circumflex (change in mean arterial pressure 27 +/- 2%) coronary artery. The reflex nature of the response was proved by its disappearance after appropriate pharmacological blockades; moreover, after vagotomy, the pressor rise was maintained, the heart rate response was reduced (change in heart rate 10 +/- 2%), and the inotropic response was enhanced (rate of change of left ventricular pressure 24 +/- 3%). This suggested that the afferent pathway of the pressor reflex was in the sympathetic nerves and that a subordinate vagal depressor reflex was also operative. No pain reaction was obtained even when injecting very large amounts (1000-2000 ng/kg) of bradykinin, which, instead, induced arterial hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

The analysis of power spectral density (PSD) or RR variability in the electrocardiogram (ECG) has suggested that, in the early phase of essential hypertension, sympatho-vagal interaction is characterized by a sympathetic predominance. Recently, we have developed a high fidelity, direct arterial pressure ambulatory recording system which allows a beat by beat computer analysis of arterial pressure and heart rate. A microminiature tip transducer (Millar, diameter 0.8 mm) is inserted percutaneously into the radial artery and connected to a Holter two-channel magnetic tape recorder. The tip transducer has a wide band pass (> 1 kHz), excellent stability (congruent to 2 mmHg/24 h) and does not require a perfusion line. The overall frequency response of the entire recording-reproducing system is better than 20 Hz (-3 dB). The ECG and pressure signals are analysed with automatic autoregressive modelling algorithms to provide a quantitative estimate of blood pressure and heart rate variability through the computation of the PSD. In seven hypertensive patients, systolic arterial pressure and variance were higher during the day (157 +/- 9 mmHg and 122 +/- 9 mmHg2) than during the night (122 +/- 4 mmHg and 30 +/- 3 mmHg2). The PSD of RR and of systolic arterial pressure consisted of a predominant low frequency peak (congruent to 0.09 cycles/beat) during the day, and two peaks at low and high (congruent to 0.25 cycles/beat) frequency during the night. While RR variance was similar during both day- and night-time, a predominant low frequency peak was observed during the day.(ABSTRACT TRUNCATED AT 250 WORDS)

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 period-systolic 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 alpha, 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 systolic arterial pressure at rest and reduced arterial pressure and increased heart period significantly. This gain 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 electrocardiographic and high fidelity arterial pressure monitoring, the index alpha was significantly reduced in the hypertensive group at rest. Furthermore, when analyzed continuously over the entire 24-hour period, this index underwent minute-to-minute changes with lower values during the day and higher values during the night. We propose the index alpha 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.

We tested the hypothesis that spectral analysis of the R-R interval and systolic arterial pressure variabilities allows assessment of the dynamic changes in neural control of the cardiovascular system in men undergoing mental stress testing. Mental arithmetic increased the low-frequency components of R-R and systolic arterial pressure, i.e. markers of sympathetic activity to the SA node and the vasculature, respectively; it also decreased the high frequency component of R-R variability, a marker of vagal activity. Spectral analysis of R-R and systolic arterial pressure variabilities may be used in the clinic to test the dynamic effects of mental stress on both sympathetic and vagal activities.