Arterial and venous plasma catecholamines during submaximal steady-state exercise

Arterial and venous plasma catecholamine responses to 15 min of cycling at 60% of maximal oxygen uptake were examined 11 times during exercise and recovery in nine young men. Intra-arterial blood pressure, heart rate and oxygen uptake were recorded continuously. All variables increased significantly during the initial 4 min, after which oxygen uptake, diastolic blood pressure and arterial plasma adrenaline showed no further increase. Heart rate and plasma noradrenaline, however, continued to increase, although significantly more slowly, and were closely correlated (r = 0·81, 95% CI 0·71–0·87), as were systolic blood pressure and heart rate (r = 0·78, 95% CI 0·71–0·87). Venous plasma adrenaline showed a steady increase during the whole exercise period and thus a different response pattern from arterial plasma adrenaline. In conclusion, arterial plasma catecholamines respond to steady-state exercise by a two-phase pattern paralleling the changes in arterial blood pressure and heart rate. Venous sampling does not reveal this association.     

Cigarette smoke-induced elevation of plasma neuropeptide Y levels in man

Summary. The purpose of the present study was to evaluate whether neuropeptide Y, which coexists with noradrenaline in sympathetic nerves, may be released upon cigarette smoking. Therefore, previously non-smoking adults inhaled smoke from one cigarette once every minute during 10 min, and the effects on blood pressure, heart rate and plasma levels of noradrenaline and neuropeptide Y were analysed. A prompt rise of systolic blood pressure and heart rate (by 25 mmHg and 30 beats min^-1, respectively) was observed upon smoking. Systemic plasma levels of noradrenaline and neuropeptide Y were significantly elevated after 3 and 5 min of smoking, respectively, and reached maximal values (neuropeptide Y from 32±4 to 49± 7pmoll^-1, and noradrenaline from 0.72±0.16 to 1.8±0.44 nmol 1^-1) 2–5 min after the smoking period. It is concluded that smoking in man is associated with increased plasma levels of both noradrenaline and neuropeptide Y, suggesting release of these agents. Since neuropeptide Y is a potent vasoconstrictor, the present data suggest that this peptide may contribute to the smoke-induced cardiovascular response.     

Response of sympathetic nervous system activity to exercise in patients with congestive heart failure

To investigate the serial sympathetic nervous system response to exercise, plasma norepinephrine (NE) and epinephrine (E) concentrations were measured at rest, during each stage of treadmill exercise, and immediately and 5 minutes after exercise in 68 congestive heart failure (CHF) patients (NYHA functional class I 24, II 25, III 19) and 30 normal subjects. Circulatory responses of NYHA class II patients increased at early stages of exercise. Systolic blood pressure and double product at peak exercise were significantly lower in NYHA class III patients. Plasma NE response of NYHA class I patients was similar to that of normal subjects. However, plasma NE at rest, and during and after exercise were significantly higher in NYHA classes II and III patients than in normal subjects and NYHA class I patients (peak NE (pg ml-1); Normals: 547 +/- 37, I: 535 +/- 53, II: 867 +/- 87, III: 1033 +/- 157). There was no significant difference in plasma E levels among the four groups. NE response to exercise was augmented according to the severity of heart failure, which suggested compensatory activation of sympathetic nervous system activity. Circulatory responses were reduced in NYHA class III patients despite the exaggerated compensatory activation of the sympathetic nervous system. Blunted circulatory responses to increased NE concentration in NYHA class III patients might relate to a decreased cardiac responsiveness to sympathetic activity in severe CHF patients.     

Sympathetic activation during the cold pressor test: influence of stimulus area

Summary. The purpose of this study was to determine the effect of the size of the stimulus area on the muscle sympathetic nerve activity (MSNA), systolic arterial blood pressure (SAP), and heart rate responses to the cold pressor test. To accomplish this, these variables were measured before (control), during, and after 1·5 min of ice water immersion of either one or both hands in nine healthy subjects (aged 19–27 years). The cold stimulus elicited significant increases above control levels in all three variables under both conditions (P<0·05). Immersion of both hands produced a much greater increase in total MSNA (+366%) than immersion of a single hand (+187%) (P<0·05). However, the magnitudes of the increases in SAP and heart rate during two-hand immersion (29±6 mmHg and 10±2 beats min^-1) were not significantly different from the responses during the one-hand trials (24±5 mmHg and 6±2 beats min^-1, P>0·05). There was a strong, direct relationship between total MSNA and SAP responses during one-hand immersion (r= 0·93, P<0·001) but not during immersion of both hands (r= 0·66, P= 0·08). These findings indicate that during the cold pressor test the magnitude of the increase in sympathetic discharge to skeletal muscle, but not the systolic blood pressure response, is influenced by the size of the tissue area exposed to the stimulus.     

Effects of noradrenaline on human vagal baroreflexes

BACKGROUND. Baroreflex sensitivity (BRS) is depressed in conditions associated with high sympathetic nerve activity in proportion to circulating noradrenaline (NA) levels. Despite the prognostic importance of measurements of BRS in patients, there is little information on how high NA levels affect arterial baroreflex function.

AIM. To understand better the role of NA in cardiovascular homeostasis.

METHODS. We gave incremental intravenous NA infusions (at 50 and 100 ng/kg/min) to 12 healthy young men. We measured RR intervals and photoplethysmographic arterial pressures and estimated BRS with cross-spectral and sequence methods during metronome-guided respiration at 0.25 Hz.

RESULTS. The high NA infusion rate significantly increased respiratory-frequency (0.15-0.40 Hz) RR interval spectral power and decreased low-frequency (0.04-0.15 Hz) systolic pressure spectral power compared with baseline levels (P < 0.05 for both). Cross-spectral BRS increased from an average (± SD) baseline level of 17.3 ± 6.6 to 34.1 ± 20.8 msJmmHg at the high NA infusion rate (P < 0.05). Sequence BRS values did not increase significantly during NA infusions. The percentage of sequences with parallel changes in systolic pressures and RR intervals decreased progressively from a baseline level of 16.0 ± 12.9 to 10.1 ± 7.4 during the low NA infusion rate and to 6.2 ± 6.2% during the high rate (P < 0.05 and 0.01, respectively).

CONCLUSIONS. Increases in circulating NA to high physiological levels do not depress BRS but interfere with the close baroreflex-mediated coupling that is usually present between arterial pressure and heart rate.     

Venous plasma noradrenaline increases with age: correlation to total blood volume and long-term smoking habits

Summary. Venous plasma noradrenaline (NA), cardiac index, total blood volume, and other haemodynamic parameters were measured in 12 young (median age of 29, range 21–37 years) and 10 elderly (median age of 68, range 55–85 years) healthy male subjects in the resting supine and sitting positions. Cardiac index was equal in the two groups and did not correlate to plasma NA. Plasma NA was significantly elevated in the elderly subjects in the sitting position (2.47±0.28 vs. 1.80±0.13 nmol l^-1, P= 0.038). Elevated plasma NA levels were confined to elderly long-term smokers. Sitting plasma NA was significantly correlated to total blood volume corrected for body weight, r= -0.720, P= 0.0002, but with no difference in blood volume between smokers and non-smokers. It is concluded, that long-term smoking may result in elevated plasma NA levels seen in elderly subjects. It is suggested, that this is a compensatory mechanism to vascular dilation induced by chronic smoking.     

Heart rate recovery: autonomic determinants,methods of assessment and association with mortality and cardiovascular diseases

Cardiovascular disease (CVD) is the primary cause of mortality worldwide. Cardiac autonomic dysfunction seems to be related to the genesis of several CVDs and is also linked to the increased risk of mortality in CVD patients. The quantification of heart rate decrement after exercise – known as heart rate recovery (HRR) – is a simple tool for assessing cardiac autonomic activity in healthy and CVD patients. Furthermore, since The Cleveland Clinic studies, HRR has also been used as a powerful index for predicting mortality. For these reasons, in recent years, the scientific community has been interested in proposing methods and protocols to investigate HRR and understand its underlying mechanisms. The aim of this review is to discuss current knowledge about HRR, including its potential primary and secondary physiological determinants, as well as its role in predicting mortality. Published data show that HRR can be modelled by an exponential curve, with a fast and a slow decay component. HRR may be influenced by population and exercise characteristics. The fast component mainly seems to be dictated by the cardiac parasympathetic reactivation, probably promoted by the deactivation of central command and mechanoreflex inputs immediately after exercise cessation. On the other hand, the slow phase of HRR may be determined by cardiac sympathetic withdrawal, possibly via the deactivation of metaboreflex and thermoregulatory mechanisms. All these pathways seem to be impaired in CVD, helping to explain the slower HRR in such patients and the increased rate of mortality in individuals who present a slower HRR.     

Relationship of angiotensin II, aldosterone, arginine vasopressin, adrenaline and noradrenaline in plasma, blood and extracellular volumes to blood pressure in chronic glomerulonephritis

Blood volume, extracellular volume, blood pressure and the plasma levels of angiotensin II, aldosterone, adrenaline, noradrenaline and arginine vasopressin were determined in sixteen normotensive (group 1) and thirteen hypertensive patients (group 2) with chronic glomerulonephritis and in eleven normotensive control subjects (group 3). Blood volume and extracellular volume did not differ between the groups and no significant differences were found in any of the hormones measured when comparing group 1 or group 2 with group 3. In the hypertensives but not in the normotensives or control subjects, a highly significant positive correlation was found between diastolic blood pressure and blood volume (rho = 0.75, P less than 0.01) and between diastolic blood pressure and extracellular volume (rho = 0.74, P less than 0.01). Blood volume and extracellular volume correlated (P less than 0.05) in each of the groups. In conclusion, although no expansion of either blood or extracellular volume was found in chronic glomerulonephritis, a positive volume-pressure relationship could be demonstrated in hypertensive patients suggesting a role of volume factors in the pathogenesis in early stage chronic glomerulonephritis. The study does not give support to a major role of either angiotensin II, arginine vasopressin or catecholamines in the maintenance of nonmalignant hypertension in early stage chronic glomerulonephritis.     

High dose ascorbic acid does not reverse central sympathetic overactivity in chronic heart failure

What is known and Objective: The increased central sympathetic activity typically associated with chronic heart failure (CHF) is probably mediated by formation of reactive oxygen species (ROS) in the brain. Our objective was to undertake a trial to test our hypothesis that administration of the well‐known antioxidant and ROS scavenger ascorbic acid, would reverse or reduce the sympathetic overactivity in CHF patients. Methods: In a prospective, randomized, placebo‐controlled, double‐blind, cross‐over trial, 11 CHF patients were treated with ascorbic acid 2 g/day or placebo for 3 days. At the end of each treatment period, sympathetic nervous system activity was measured by microneurography for direct muscle sympathetic nerve activity (MSNA) recording, analysis of heart rate variability (HRV) and measurement of plasma norepinephrine concentrations. Results: During ascorbic acid administration, plasma vitamin C levels were higher than during placebo (74·9 ± 6·0 μmol/L vs. 54·8 ± 4·6 μmol/L, P = 0·03). Ascorbic acid had no effect on sympathetic activity: MSNA (ascorbic acid: 66·8 ± 3·3 vs. placebo 66·9 ± 3·2 bursts/100 beats, P = 0·98). In addition, HRV and plasma norepinephrine levels did not differ. What is new and Conclusion: Short‐term administration of the antioxidant ascorbic acid in CHF patients does not reverse the increased sympathetic activity as measured by microneurography, HRV and plasma norepinephrine levels. The use of higher oral dosages seems not feasible due to accompanying side effects.     

Spontaneous baroreflex by sequence and power spectral methods in humans,

Summary. Beat-by-beat variations in blood pressure and RR-interval are interrelated by the actions of baroreflex and non-baroreflex responses. This study had two purposes: (1) to examine the spontaneous relationships between RR-interval and systolic blood pressure to determine the relative occurrence of baroreflex and non-baroreflex responses in humans, and (2) to compare the beat-sequence method with a cross spectral estimate of the baroreflex response slope. Eight healthy men were studied during 10 h of quiet, seated rest, and six men and three women were studied during rest, rest plus fixed pace breathing, and a cold pressor test. RR-interval and continuous, non-invasive arterial blood pressure were measured with a computerized system. A baroreflex sequence was defined by a series of at least three consecutive heart beats in which systolic pressure and the following RR-interval either both increased or both decreased. A non-baroreflex relationship was defined by sequences of at least three beats by opposite directional changes of RR-interval and systolic pressure of that beat. The results showed that there were approximately 30% as many non-baroreflex compared to baroreflex slopes. Individual subject mean baroreflex and non-baroreflex slopes were highly correlated (r= 0–72, P < 0–001). Absolute slope values were not different, and they were unaffected by time, fixed pace breathing, or cold pressor test. The data showed the relatively simple beat-by-beat sequence method to yield spontaneous baroreflex response slopes that were quantitatively similar to, and highly correlated with (r= 0–85-0-94), baroreflex response slopes calculated by spectral analysis methods.     

Cluster headache: Heart rate and blood pressure changes during spontaneous attacks

The ECG findings before, during and following 81 spontaneous attacks of cluster headache in 24 patients have been recorded using a Holter cardiography system. No significant change in mean heart rate was found during attacks, when all attacks were considered as a group. Attacks which began when patients were awake differed from those which began during sleep as regards changes in mean heart rate. The mean heart rate decreased during the majority (61%) of attacks which began when patients were awake, whereas it remained unchanged or increased during the majority (67.5%) of attacks which began during sleep. The attacks which began when patients were awake also had higher absolute mean heart rate values before, during and following attacks compared to similar values for those attacks which began during sleep. Blood pressure was measured during 11 attacks and showed a significant increase in both systolic and diastolic blood pressure. The heart rate and blood pressure in six patients usually increased during induced head pain.     

Combination of low blood pressure response,low exercise capacity and slow heart rate recovery during an exercise test significantly increases mortality risk

Abstract

Aims: We investigated the combination of low systolic blood pressure (SBP) response, low exercise capacity (EC) and slow heart rate recovery (HRR) during an exercise test in mortality prediction.

Patients and methods: Our population consisted of 3456 patients from the Finnish Cardiovascular Study. A failure of SBP to increase >42?mmHg was defined as a low response. Low EC was defined as <?8 metabolic equivalents. 1-minute HRR ≤18 bpm from maximum was defined as slow HRR.

Results: During a median follow up of 10.0?years, 537 participants died. Reduced SBP response, low EC and slow HRR were independent predictors of all-cause and CV mortality (p?<?.001 for all). Patients with reduced SBP response, low EC and slow HRR had a very high mortality rate of 42.1% during follow up compared to only 4.5% of the patients without any of these risk factors. The hazard ratios for all-cause mortality in patients with one, two or three of the studied risk factors were 3.2, 6.0, and 10.6, respectively (p?<?.001 for all).

Conclusion: The combination of reduced SBP response, low exercise capacity, and reduced HRR in an exercise test is associated with very high mortality and can be used in risk stratification.

• Key messages

• The combination of low blood pressure response, low exercise capacity and slow heart rate recovery in an exercise test is able to identify a group of patients in a very high mortality risk.

• These parameters are easily derived from an exercise test.

• All parameters are commonly available in clinical practice.

     

Plasma endothelin-1 during central hypovolaemia in man

Summary. Endothelin-1 (ET-1) is a potent vasoconstricting peptide with effect on resistance as well as capacitance vessels. We followed ET-1 in arterial plasma together with heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and thoracic electrical impedance (TI) in seven men during central hypovolaemia induced by 50± head-up tilt. During tilting plasma ET-1 increased from 1.1 ±0.2 to 1.4 ± 0.3 pmol 1^-1 (mean ± SE) concomitant with an increase in total peripheral resistance (TPR) (from 15 ± 2 to 25 ± 3 mmHg min 1^-1) (P< 001), and HR (from 67 ± 2 to 94 ± 5 beats min^-1) (P<0.01) while MAP remained unchanged. CVP decreased (from 1.8±0.9 to -1.6±1.0 mmHg) (P<0.01) during tilting and remained unchanged during sustained tilt despite further reduction of central blood volume as recorded by TI. Presyncopal symptoms occurred after 28 ± 6 min associated with decreases in HR (to 70 ± 6 beats min^-1), MAP (from 90 ± 3 to 52 ± 4 mmHg) and TPR (to 11 ± 2 mmHg min l^-1) (P<0.01). At this time plasma ET-1 reached its highest level of 1.6±0.3 pmol l^-1 (P<0.01). Data show that head-up tilt is associated with increased plasma concentrations of ET-1 which may play a role in maintaining vascular tone in situations with a reduced central blood volume.     

Heart rate and blood pressure variability in cardiac diseases: pharmacological implications

Summary— Even at rest, blood pressure and heart rate fluctuate continuously around their mean values. Considerable interest has recently focused on the assessment of spontaneous fluctuations in heart rate and blood pressure, ie, heart rate and blood pressure variability, using time or frequency domain indexes. Heart rate variability has been extensively studied in cardiovascular disease and has emerged as a valuable parameter for detecting abnormalities in autonomic cardiovascular control, evaluating the prognosis and assessing the impact of drug therapy on the autonomic nervous system in patients with myocardial infarction, congestive heart failure or a heart transplant. In contrast, until the recent development of noninvasive methods for continuous blood pressure recording, blood pressure variability received little attention, and this parameter remains to be evaluated in cardiovascular disease.     

Comparison of Polar® RS800G3™ heart rate monitor with Polar® S810i™ and electrocardiogram to obtain the series of RR intervals and analysis of heart rate variability at rest

The Polar^® RS800G3^? rate monitor was released in the market to replace the Polar^® S810i^?, and few studies have assessed that the RR series obtained by this equipment is reliable for analysis of heart rate variability (HRV). We compared HRV indexes among the devices Polar^® RS800G3^?, Polar^® S810i^? and eletrocardiogram (ECG) to know whether the series of Polar^® RS800G3^? are as reliable as those devices already validated. We analysed data from 30 healthy young adults, male, with an average age of 20·66 ± 1·40 years, which had captured the heart rate beat to beat in the three devices simultaneously with spontaneously breathing, first in the supine position and subsequently sit both for 30 min. The obtained series of RR intervals was used to calculate the indexes of HRV in the time domain (SDNN and RMSSD) and in the frequency domain (LF, HF and LF/HF). There were no significant differences in HRV indexes calculated from series obtained by the three devices, regardless of the position analysed, and a high correlation coefficient was observed. The results suggest that the Polar^® RS800G3^? is able to capture series of RR intervals for analysis of HRV indexes as reliable as those obtained by ECG and Polar^® S810i^?.     

Plasma noradrenaline and ageing: effects of smoking habits

Abstract. We tested the hypothesis that long-term smoking is responsible for increased plasma noradrenaline (NA) in elderly healthy subjects. Thirty-nine subjects were studied both at rest and during exercise: 10 young non-smokers (median age 24 years, range 21–33), 10 young smokers (30.5 years, 27–36), 10 elderly non-smokers (64 years, 52–75) and nine elderly smokers (62 years, 56–68). The young and elderly subjects had smoked for an average of 15 years and 46.8 years respectively. Plasma NA was significantly elevated in elderly long-term smokers compared with elderly non-smokers, young non-smokers and young smokers in both supine and sitting positions (supine: 1.06 ± 0.24 vs. 0.71 ± 0.22, 0.53 ± 0.12, and 0.70 ± 0.29 nmolL^-1 respectively; sitting: 3.01 ± 0.83 vs. 2.07 ± 0.77, 1.89 ± 0.52 and 2.25 ± 0.47 nmol L^-1 respectively). Plasma adrenaline did not differ among the groups. At submaximal exercise (60 W), plasma NA was significantly elevated in the elderly smokers compared with the other groups, owing to the elevated basal values. Increments in plasma NA at 60, 100 and 140 W were correlated with the relative exertion and not influenced by smoking. Plasma NA increased more in young subjects than in the elderly during maximal work load (21.7 ± 8.0 vs. 13.4 ± 5.4 nmol L^-1) and correlated with the peak O₂ uptake. Total blood volume was not different among the four groups and correlated inversely with basal plasma NA. It is concluded that long-term smoking may contribute to increased basal plasma NA concentrations and probably also increased sympathetic nerve activity in elderly healthy subjects, whereas smoking has little if any effect on plasma NA responses induced by exercise. Interindividual variability in basal plasma NA concentrations may in part be explained by differences in blood volume.     

Effect of posture on baroreflex sensitivity in healthy subjects

Summary. In this study we investigated whether body position has significant effects on baroreflex sensitivity in healthy subjects. Baroreflex sensitivity was calculated from pressure overshoot after the release of a Valsalva strain in the supine and sitting positions in 10 subjects. At rest, no difference was found in supine and sitting mean R-R intervals (837±82 and 858±86 ms, respectively), whereas systolic and diastolic blood pressures were lower in the supine position (111.3±24.6 vs. 141.2±12.6 mmHg, P<0.01 and 54.8±14.7 vs. 75.6±13.4 mmHg, P<0.001, respectively). Baroreflex sensitivity in the supine (9.0±4.1 ms±mmHg^-1) and sitting positions (8.8±4.9 msXmmHg^-1) did not differ significantly from each other. The correlation between supine and sitting baroreflex sensitivity was 0.96 (P<0.001) and in 9 out of 10 subjects the discrepancy between supine and sitting baroreflex sensitivity was <2.0 ms±mmHg^-1. We conclude that baroreflex sensitivity measured in the supine and sitting positions do not differ significantly from each other.     

Effect of non-hypotensive haemorrhage on plasma catecholamine levels and cardiovascular variability in man

Background: It is well known from animal research that non‐hypotensive haemorrhage produces sympathoexcitatory responses assessable by both the rise in plasma catecholamine levels and the shift of autonomic influences on the heart to more sympathetic and less parasympathetic control. Data in humans are restricted. Methods: Heart rate variability (HRV), systolic blood pressure (FINAPRES) variability (BPV), and catecholamine plasma levels were measured before and after haemorrhage in 30 healthy blood donors and compared with those from 10 control subjects without blood loss. Spectral power of HRV and BPV in very low (0·02–0·06 Hz), low (0·07–0·14 Hz), and high (0·15–0·40 Hz) frequency bands were calculated by Fourier analysis. Catecholamine plasma levels were assayed by dual column reverse‐phased high‐performance liquid chromatography (HPLC). Results: Haemorrhage of 5·6 ± 1·2 ml kg^?1 body weight increased plasma norepinephrine levels (215 ± 92 pg ml^?1 versus 254 ± 95 pg ml^?1; P = 0·002), increased BPV in the low frequency band (Mayer waves; 1·8 ± 1·0 ln [mmHg²] versus 2·0 ± 0·9 ln [mmHg²]; P = 0·021), and decreased the vagally transmitted high frequency HRV (6·9 ± 1·1 ln [MI²] versus 6·5±1·2 ln [MI²]; P<0·0001), but did not induce significant changes in heart rate (66 ± 11 bpm versus 67 ± 11 bpm; P = 0·79) and arterial blood pressure (mean values: 84 ± 13 mmHg versus 87 ± 13 mmHg; P = 0·12). Conclusions: As suggested by plasma norepinephrine levels, systolic BPV and HRV, non‐hypotensive haemorrhage produces sympathoexcitatory responses as well as vagal withdrawal of heart rate control in humans.     

Muscle sympathetic nerve activity during isometric exercise in patients with cerebrovascular accidents

OBJECTIVES: To define isometric exercise-induced pressor responses in patients with cerebrovascular accidents (CVAs) and to assess potential cardiovascular and sympathetic nervous system abnormalities during isometric exercise in CVA. DESIGN: Nonrandomized study. SETTING: University laboratory setting. PARTICIPANTS: Eight men with CVA who had documented damage of subcortical structures and 8 sex-matched controls. INTERVENTIONS: A 2-minute sustained contraction of elbow flexor muscles in the unaffected side at 35% of maximal voluntary contraction (MVC; isometric exercise). MAIN OUTCOME MEASURES: Heart rate, arterial blood pressure, and muscle sympathetic nerve activity (MSNA), recorded from the peroneal nerve on the affected side. RESULTS: The percent changes in total MSNA, heart rate, and mean blood pressure in patients with CVA increased during isometric exercise but were attenuated compared with the controls. Total MSNA (mean burst amplitude per minute times burst rate) increased significantly in CVA and control subjects during isometric exercise by 18.7%+/-6.3% and 95.8%+/-25.2%, respectively. CONCLUSIONS: The attenuated pressor responses during isometric exercise in subjects with CVA relative to the controls indicated damage to subcortical structures; such damage lowered sympathetic nervous response to isometric exercise. Our findings suggest that isometric exercise at 35% of MVC does not put patients with CVA at risk for serious tachycardia or hypertension.