Giovanni Bertinieri

Blood pressure and heart rate variabilities in normotensive and hypertensive human beings.

Blood pressure and heart rate variabilities were studied in 89 ambulant normotensive or essential hypertensive subjects in whom blood pressure was recorded intra-arterially for 24 hours (Oxford method) under standardized living conditions. Data were analyzed beat to beat by a computer to provide mean values of the 48 half hours of the 24-hour period. Variabilities were assessed by the standard deviation and variation coefficients separately obtained for each half hour, as well as by the standard deviations and variation coefficients obtained by averaging the 48 mean values. In each subject, blood pressure and heart rate varied markedly either among or within half hours, indicating the existence of relatively long- and short-term variabilities during the 24 hours. When averaged for all subjects, the long-term variabilities showed only one systematic component, i.e., the marked reduction occurring during sleep. Sleep was further responsible for a marked reduction in the short-term blood pressure and heart rate variabilities. These variabilities showed marked (though nonsystematic) modifications, even outside sleep, which were positively related to the blood pressure and heart rate means. Modifications in blood pressure and heart rate means and short-term variabilities were also positively related to each other. All these features were common to normotensives and hypertensives. In hypertensives, the absolute long and short-term blood pressure variabilities were greater than in normotensives, but the percent blood pressure variabilities were similar. Heart rate variabilities (both absolute and percent) were similar in normotensive and hypertensive subjects. Heart rate variabilities were also similar whether the subjects had impaired or preserved baroreflex control of heart rate (vasoactive drug technique). These findings uncover a number of factors that are associated with and responsible for blood pressure and heart rate variabilities in human beings. The nature of these factors suggest a primary role of central nervous mechanisms in the production of these phenomena and in the overall cardiovascular modulation, with no substantial difference between conditions of normal and chronically elevated blood pressure.

EFFECTS OF BLOOD-PRESSURE MEASUREMENT BY THE DOCTOR ON PATIENT'S BLOOD PRESSURE AND HEART RATE

Changes in blood pressure in 10 or 15 min periods during which a doctor repeatedly measured blood pressure by the cuff method were monitored by a continuous intra-arterial recorder. In almost all the 48 normotensive and hypertensive subjects tested the doctors arrival at the bedside induced immediate rises in systolic and diastolic blood pressures peaking within 1 to 4 min (mean 26.7 +/- 2.3 mm Hg and 14.9 +/- 1.6 mm Hg above pre-visit values). There were large differences between individuals in the peak response (range, 4--75 mm Hg systolic and 1--36 mm Hg diastolic) unrelated to age, sex, baseline blood pressure, or blood-pressure variability. There was concomitant tachycardia (average peak response 15.9 +/- 1.5 beats/min, range 4--45 beats/min) which was only slightly correlated with the blood-pressure rise. After the peak response blood pressure declined and at the end of the visit was only slightly above the pre-visit level. A second visit by the same doctor did not change the average size of the early pressor response or the slope of its subsequent decline.

Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans.

The baroreceptor control of the sinus node was evaluated in 10 normotensive and 10 age-matched essential hypertensive subjects in whom ambulatory blood pressure was recorded intraarterially for 24 hours and scanned by a computer to identify the sequences of three or more consecutive beats hi which systolic blood pressure (SBP) and pulse interval (PI) progressively rose (+ PI/ + SBP) or fell (− PI/ −SBP) in a linear fashion, according to a method validated in cats. In normotensive subjects, several hundred +PI/+SBP and −PI/−SBP sequences of 3 beats were found whereas the number of sequences of 4,5, and more than 5 beats showed a progressive drastic reduction. The mean slopes of plus; PI/ + SBP (7.6 ± 2.0 msec/mm Hg) and − PI/− SBP (6.4 ± 1.5 msec/mm Hg) sequences were similar, but in both instances there was a large scattering of the values around the mean (variation coefficients: 64.2 ± 4.7 and 62.6 ± 2.4%). The slopes decreased as a function of the sequence length and baseline heart rate and increased to a marked extent during the night as compared with daytime values. All sequences were more rare (−33.2% for +PI/ + SBP and −31.7% for −PI/−SBP) and less steep in hypertensive subjects (−40.3 and −36.2%, respectively), who failed to show the marked nighttime increase in slope observed in normotensive subjects. To our knowledge, these observations provide the first description in humans of the baroreceptor-heart rate reflex in daily life. This reflex is characterized by marked within-subject variations hi sensitivity due in part to hemodynamic, temporal, and behavioral factors. All features of the baroreceptor-heart rate reflex are unpaired hi essential hypertension.

Heart rate as marker of sympathetic activity.

Objective To determine the value of the supine heart rate as a marker of sympathetic tone by assessing, in a large group of subjects, the relationships between this parameter and two other indices of sympathetic activity, plasma norepinephrine and sympathetic nerve traffic. Patients and methods We studied 243 subjects aged 50.0 ± 12.1 years (mean ± SD). Of these, 38 were normotensive healthy controls, 113 subjects had untreated essential hypertension, 27 were obese normotensives and 65 had congestive heart failure. In each subject, over a 10 min supine period, we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), venous plasma norepinephrine (high-performance liquid chromatography) and efferent postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). Results In the whole study group, supine heart rate was correlated with both plasma norepinephrine (r = 0.32, P < 0.0001) and muscle sympathetic nerve activity (r = 0.38, P < 0.0001). This was also the case in the normotensive obese subjects and the heart failure subjects considered separately. Heart rate values were greater in the obese and the heart failure patients than in controls (75.1 ± 13.0 and 78.2 ± 13.0 versus 69.2 ± 11.6 beats/min; P < 0.05 and P < 0.001, respectively), as were plasma norepinephrine (362.7 ± 202 and 400.3 ± 217 versus 230.4 ± 126 pg/ml; P < 0.01 and P < 0.001, respectively) and muscle sympathetic nerve activity (44.1 ± 14.7 and 55.3 ± 14.3 versus 27.8 ± 11.0 bursts/min; P < 0.001 for both). In contrast, in the essential hypertensive subjects, no significant relationship was found between these three indices of sympathetic activity. Furthermore, in the hypertensives, the heart rate was not increased, at variance with the sympathetic nerve traffic, which was greater than in controls (36.2 ± 10.0 versus 27.8 ± 11.0 bursts/min, P < 0.001). Conclusions These data suggest that the supine heart rate can be regarded as a marker of intersubject differences in sympathetic tone, and that this is the case both in the general population and in those with cardiovascular diseases. Its value for this purpose is limited, however, and the limitations may be more evident in essential hypertension than in conditions such as obesity and heart failure.

Modification of arterial baroreflexes by captopril in essential hypertension

Captopril lowers blood pressure without increasing heart rate and plasma norepinephrine, which suggests that this drug may potentiate arterial baroreflexes. In eight subjects with untreated essential hypertension, blood pressure was monitored intraarterially and the effects of baroreceptor stimulation or deactivation were assessed by measuring (1) the slopes of the relations between increase or reduction in systolic pressure (intravenous phenylephrine or nitroglycerin) and the resulting lengthening or shortening in R-R interval, and (2) the increase or decrease in mean arterial pressure induced by increasing and decreasing carotid transmural pressure (neck chamber). The measurements were made before and after a hypotensive oral dose of captopril (50 mg). Before captopril, the slopes of the R-R interval changes with increase and reduction in systolic pressure were 8 and 4 ms/mm Hg, respectively. The slopes of the mean arterial pressure changes with increase and reduction in carotid transmural pressure were 0.51 and 0.40 mm Hg, respectively. After captopril, the responses to baroreceptor stimulation were unaltered but those to baroreceptor deactivation were augmented. The pressor and heart rate responses to hand-grip and cold exposure were unchanged by captopril. Administration of captopril is accompanied by a baroreflex potentiation which involves the lower portion of the stimulus-response curve of the reflex. This phenomenon (which may originate at the afferent baroreceptor fibers or centrally) may avoid a reduction in the tonic baroreflex influence during captopril-induced hypotension, thus contributing to the hemodynamic effects of the drug.

Sympathetic and reflex alterations in systo-diastolic and systolic hypertension of the elderly

Background Previous studies have shown that young and middle-aged essential hypertensives are characterized by a sympathetic activation coupled with an impaired baroreflex-heart rate control. The present study aimed to determine whether these neuroadrenergic and reflex alterations also characterize systo-diastolic and systolic hypertension of the elderly. Subjects and methods In 20 untreated elderly essential hypertensive subjects [10 with a systo-diastolic and 10 with an isolated systolic hypertension, aged 67.2 ± 1.5 years and 66.9 ± 1.7 years (mean ± SEM)], we measured beat-to-beat arterial blood pressure (finger photoplethysmographic device), heart rate (electrocardiogram) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Data were compared with those obtained in 11 age-matched normotensive control subjects. Results Compared to the elderly normotensive group, muscle sympathetic nerve activity was increased to a similar degree in the group of systo-diastolic and systolic hypertension (50.8 ± 4.2 versus 75.2 ± 5.2 and 70.4 ± 5.1 bursts per 100 heart beats, respectively, P <0.01 for both). In the control group, the stepwise increase in arterial pressure induced by phenylephrine caused progressive bradycardia and sympathoinhibition, while the stepwise decrease in arterial pressure had opposite effects. While baroreceptor-heart rate control was markedly impaired (average reduction 41.6%), in both systo-diastolic and systolic hypertensive patients, baroreceptor modulation of sympathetic nerve traffic was similar to that seen in normotensive individuals. Conclusions These data demonstrate that sympathetic activation is not only a feature of young and middle-aged, but also of elderly hypertensives, regardless of whether both systolic and diastolic or only systolic blood pressure is increased. They also show that hypertension of the elderly is not accompanied by an impaired baroreceptor modulation of sympathetic nerve traffic.

Impairment of Thermoregulatory Control of Skin Sympathetic Nerve Traffic in the Elderly

Background—Human aging is characterized by a marked increase in muscle sympathetic nerve traffic (MSNA). No information exists, however, on the effects of aging on skin sympathetic nerve traffic (SSNA) and on its reflex modulation by thermoregulatory mechanisms. Methods and Results—In 13 young, 11 middle-aged, and 12 elderly healthy subjects, we measured arterial blood pressure (Finapres), skin temperature (thermocouples), and resting MSNA and SSNA (microneurography). Measurements also included the SSNA responses to (1) an acute increase and reduction (±8°C) in room temperature, each lasting 45 minutes and (2) an acoustic stimulus capable to trigger an emotional arousal. Although resting MSNA was progressively and significantly (P <0.05) increased from young to middle-aged and elderly groups, SSNA was significantly (P <0.05) reduced in the latter compared with the former 2 groups. Cold exposure induced a SSNA increase that was significantly (P <0.01) smaller in the elderly than in young and middle-aged subjects. Conversely, heat exposure induced a SSNA reduction that was significantly (P <0.05) smaller in elderly than in young and middle-aged subjects. Compared with SSNA in young individuals, the SSNA change from cold to warm temperature was reduced by 61% in the elderly group. This was not the case, however, for the SSNA responses to the arousal stimulus, which were superimposable in the 3 groups. Conclusions—These data provide the first demonstration of a dichotomy in the MSNA and SSNA responses to aging. They also show that aging markedly impairs thermoregulatory control of SSNA and that this impairment might participate at the age-related SSNA decrease.

Reflex control of blood pressure and heart rate by arterial baroreceptors and by cardiopulmonary receptors in the unanaesthetized cat.

Studies in unanaesthetized animals have reported that section of the carotid sinus and aortic nerves is accompanied by an increased blood pressure variability but not by a sustained blood pressure rise, thus questioning the role of arterial baroreceptors in the long term control of mean blood pressure values. However, sino-aortic denervation (SAD) does not produce denervation of all baroreceptor areas, and it has been suggested that aortic baroreceptor fibres in the vagus and cardiopulmonary vagal afferents that restrain sympathetic vasoconstrictor tone prevent blood pressure from permanently rising. In unanaesthetized cats we recorded blood pressure intra-arterially for 8-12 h when baroreflexes were intact, 7 days after SAD and 1-2 days additional bilateral cervical vagotomy. Blood pressure signals were analysed by computer to provide means and coefficients of variation (CV, variabilities) for each recording period. In intact cats, mean blood pressure was 99 +/- 7 mmHg (average +/- s.e.) and CV 6 +/- 1%. SAD did not alter mean blood pressure but markedly increased CV (12 +/- 2%; P less than 0.01). Additional vagotomy did not alter mean blood pressure (104 +/- 6 mmHg), nor did it alter the increased CV observed after SAD alone. Vagotomy failed to affect mean blood pressure and CV even when performed in cats with intact carotid and aortic nerves. The lack of effect of vagotomy did not depend on simultaneous section of afferent and efferent fibres, because selective blockade of the latter by atropine also failed to affect mean blood pressure and CV.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathetic and reflex abnormalities in heart failure secondary to ischaemic or idiopathic dilated cardiomyopathy

Congestive heart failure (CHF) is characterized by a sympathetic activation and a baroreflex impairment whose degree is directly related to the clinical severity of the disease. However, whether these abnormalities vary according to the ischaemic or idiopathic dilated nature of the CHF state has not been conclusively documented. In patients with a clinically stable, chronic CHF state in New York Heart Association functional class II and III, due either to ischaemic heart disease (IHD; n=22, age 60.3+/-2.4 years, means+/-S.E.M.) or to idiopathic dilated cardiomyopathy (IDC; n=20, age 58.9+/-2.8 years), and in 30 age-matched controls, we measured arterial blood pressure (using a Finapres device), heart rate (by electrocardiogram) and postganglionic muscle sympathetic nerve traffic (by microneurography) at rest and during baroreceptor manipulation induced by the vasoactive drug-infusion technique. Blood pressure values were not significantly different in CHF patients and controls. Compared with controls, heart rate was similarly increased and left ventricular ejection fraction (by echocardiography) similarly reduced in CHF patients with IHD or IDC. Muscle sympathetic nerve traffic was significantly greater in CHF patients than in controls, and did not differ between patients with IHD or IDC (67.3+/-4.2 and 67.8+/-3.8 bursts/100 heart beats respectively). This was also the case for the degree of baroreflex impairment. These data show that CHF states due to IHD or to IDC are characterized by a similar degree of peripheral sympathetic activation and by a similar impairment of the baroreflex function. Thus the neuroadrenergic and reflex abnormalities characterizing CHF are independent of its aetiology.

Hemodilution Reduces Clinic and Ambulatory Blood Pressure in Polycythemic Patients

Limited information is available for humans on whether blood viscosity affects total peripheral resistance and, hence, blood pressure. Our study was aimed at assessing the effects of acute changes in blood viscosity on both clinic and 24-hour ambulatory blood pressure (BP) values. In 22 normotensive and hypertensive patients with polycythemia, clinic and 24-hour ambulatory BPs were measured before and 7 to 10 days after isovolumic hemodilution; this was performed through the withdrawal of 400 to 700 mL of blood, with concomitant infusion of an equivalent volume of saline-albumin solution. Hematocrit, plasma renin activity, plasma endothelin-1, right atrial diameter (echocardiography), and blood viscosity were measured under both conditions. Plasma renin activity and right atrial diameter were used as indirect markers of blood volume changes. Plasma endothelin-1 was used to obtain information on a vasomotor substance possibly stimulated by our intervention, which could counteract vasomotor effects. Isovolumic hemodilution reduced hematocrit from 0.53+/-0.05 to 0.49+/-0.05 (P<.01). Plasma renin activity, plasma endothelin-1 and right atrial diameter were unchanged. Clinic blood pressure was reduced by hemodilution (systolic, 144.3+/-5.4 to 136.0+/-3.9 mm Hg[mean+/-SEM]; diastolic, 87.0+/-2.8 to 82.1+/-2.6 mm Hg, P<.05 for both) and a reduction was observed also for 24-hour average ABP (systolic, 133.6+/-2.9 to 129.5+/-2.7 mm Hg; diastolic, 80.0+/-2.0 to 77.3+/-1.7 mm Hg, P<.05 for both). The reduction was consistent in hypertensive patients (n = 12), whereas in normotensive patients (n = 10) it was small and not significant. Both clinic and 24-hour average heart rates were unaffected by the hemodilution. Thus, in polycythemia, reduction in blood viscosity without changing blood volume causes a significant fall in both clinic and 24-hour ambulatory BPs; this is particularly true when, as can often happen, blood pressure is elevated. This emphasizes the importance this variable may have in the determination of blood pressure and the potential therapeutic value of its correction when altered.