Atrial septal defect patients have an elevated risk for infective endocarditis.

Background. It has been unclear whether simple atrial septal defect (ASD) is an independent risk factor for infective endocarditis (IE). This study aimed to untangle the risk of endocarditis in a large nationwide cohort. Methods. We acquired data from the Finnish hospital discharge register on all individuals with ASD diagnosis from 1969 to 2019. Patients with complex congenital cardiac abnormalities were ruled out. Five individualized controls from the general population were matched to the ASD patient's birth year, sex, and residence at the index date. All the patients with ICD-8, -9, or -10 diagnosis codes for IE were gathered from the hospital discharge registry. Results. Altogether, 8322 patients with ASD and 39,237 individualized controls were enrolled in the study. Median follow-up was 21.6 years (IQR 11.8-36.9) from the first hospital contact. In total, 24 (16 male) cases of infective endocarditis among ASD patients and 10 (8 male) cases among controls were diagnosed during the follow-up. The incidence of endocarditis was 0.11 per 1000 person-years in the patients with ASD and 0.011 per 1000 person-years in the controls. The adjusted risk ratio for endocarditis was 13.51 (95% CI: 6.20-29.46) in patients with ASD compared to the control cohort. Patients with ASD and endocarditis had higher long-term mortality than individualized control patients (MRR 2.25, 95% CI: 1.23-4.11). Conclusions. The incidence of IE in patients with ASD was higher than in the general population. Mortality associated with IE was higher in patients with ASD compared to controls.

Resting heart rate predicts cardiac autonomic modulation during passive head-up tilt in subjects without cardiovascular diseases.

Background Resting heart rate (HR) and its variability (HRV) reflects the cardiac sympathovagal balance that is stimulated by head-up tilting. HRV is influenced by the level of HR, but how much HRV offers additional information about cardiac autonomic tone than HR alone remains unresolved. We examined the relation of resting HR with HRV during head-up tilt. Methods. Hemodynamics of 569 subjects without known cardiovascular diseases and medications with direct cardiovascular effects were recorded using whole-body impedance cardiography, radial pulse wave analysis, and electrocardiography-based HRV analysis during passive head-up tilt. Results. Higher low frequency to the high-frequency ratio (LF/HF) of HRV (reflecting sympathovagal balance) was associated with higher HR in supine (p < .05, both linear regression analysis and variance analysis comparing HR tertiles) and upright postures (p < .001, linear regression analysis). The association of HR with HRV during tilt-testing remained significant when the HR dependence of HRV was mathematically weakened by dividing the HRV power spectra with the fourth power of the average RR-interval. Conclusion. Higher resting HR is related to higher LF/HF both supine and upright, reflecting elevated sympathetic influence on cardiac autonomic modulation. Lower resting HR is associated with lower resting LF/HF, while the differences in LF/HF between the HR tertiles were minor during head-up tilt, suggesting a greater change in cardiac sympathovagal balance in response to upright posture in those with lowest resting HR. Altogether, resting HR well predicts HRV levels during head-up tilt.Trial registration: Clinicaltrialsregister.eu 2006-002065-39, first registered 5 May 2006. ClinicalTrials.gov NCT01742702, first registered 5 December 2012.

Disparate Information Provided by Pulse Wave Velocity versus Other Measures of Aortic Compliance in End-Stage Renal Disease.

INTRODUCTION: Unfavorable changes in cardiac and arterial function are related to poor prognosis in chronic kidney disease (CKD). We compared hemodynamic profiles between subjects with end-stage renal disease and 2 control groups with corresponding pulse wave velocities (PWVs). METHODS: Noninvasive hemodynamics were recorded during passive head-up tilt in CKD stage 5 patients (n = 35), patients with primary hypertension (n = 35, n = 30 with antihypertensive medications), and subjects without cardiovascular or renal diseases and cardiovascular medications (n = 70). The groups were selected to have corresponding age, sex, body mass index, and PWV. Hemodynamic data were captured using whole-body impedance cardiography and radial tonometric pulse wave analysis. RESULTS: Supine blood pressure did not differ between the groups, but upright diastolic blood pressure was lower in CKD patients than in the 2 control groups (p ≤ 0.001 for both, RANOVA). Despite similar PWV, supine aortic pulse pressure was higher in CKD patients versus nonmedicated subjects (p = 0.029). Two additional measures indicated reduced aortic compliance in CKD patients versus both control groups: lower ratio of stroke index to aortic pulse pressure (p ≤ 0.023) and higher aortic characteristic impedance (p ≤ 0.003). The subendocardial viability ratio was lower in the CKD group than in both control groups (p ≤ 0.039). CONCLUSION: In the absence of differences in PWV, higher aortic pulse pressure and characteristic impedance, and lower ratio of stroke index to aortic pulse pressure, suggest reduced aortic compliance and impaired left ventricular function in CKD patients. A lower subendocardial viability ratio predisposes the CKD patients to impaired cardiac oxygen supply versus hypertensive patients and nonmedicated controls.

Salbutamol-induced Decrease in Augmentation Index is Related to the Parallel Increase in Heart Rate.

The change in augmentation index following salbutamol inhalation has been applied to evaluate endothelial function. We examined the contribution of salbutamol-induced increase in heart rate to the observed decrease in augmentation index. Haemodynamics were recorded using whole-body impedance cardiography and continuous pulse wave analysis from tonometric radial blood pressure. All subjects (n = 335, mean age 46, body mass index 26, 48% men) were without medications with cardiovascular influences. The effects of salbutamol inhalation (0.4 mg) versus the endothelium-independent agent nitroglycerin resoriblet (0.25 mg) were examined during passive head-up tilt, as the haemodynamic influences of these compounds depend on body position. Salbutamol decreased augmentation index by ~3-4% units in supine and upright positions. Although salbutamol moderately increased cardiac index (+4.5%) and decreased systemic vascular resistance (-8.5%), the significant haemodynamic explanatory factors for decreased augmentation index in multivariate analysis were increased supine heart rate, and increased upright heart rate and decreased ejection duration (p < 0.001 for all, r2  = 0.36-0.37). Sublingual nitroglycerin decreased supine and upright augmentation index by ~15% units and ~23% units, respectively. The haemodynamic explanatory factors for these changes in multivariate analysis were increased heart rate, reduced ejection duration and reduced systemic vascular resistance (p ≤ 0.021 for all, r2  = 0.22-0.34). In conclusion, the lowering influence of salbutamol on augmentation index may be largely explained by increased heart rate, suggesting that this effect may not predominantly reflect endothelial function.

Voluntary liquorice ingestion increases blood pressure via increased volume load, elevated peripheral arterial resistance, and decreased aortic compliance.

We investigated the haemodynamic effects of two-week liquorice exposure (glycyrrhizin dose 290-370 mg/day) in 22 healthy volunteers during orthostatic challenge. Haemodynamics were recorded during passive 10-minute head-up tilt using radial pulse wave analysis, whole-body impedance cardiography, and spectral analysis of heart rate variability. Thirty age-matched healthy subjects served as controls. Liquorice ingestion elevated radial systolic (p < 0.001) and diastolic (p = 0.018) blood pressure and systemic vascular resistance (p = 0.037). During orthostatic challenge, heart rate increased less after the liquorice versus control diet (p = 0.003) and low frequency power of heart rate variability decreased within the liquorice group (p = 0.034). Liquorice intake increased central pulse pressure (p < 0.001) and augmentation index (p = 0.002) supine and upright, but in the upright position the elevation of augmentation index was accentuated (p = 0.007). Liquorice diet also increased extracellular fluid volume (p = 0.024) and aortic to popliteal pulse wave velocity (p = 0.027), and aortic characteristic impedance in the upright position (p = 0.002). To conclude, in addition to increased extracellular fluid volume and large arterial stiffness, two weeks of liquorice ingestion elevated systemic vascular resistance and augmentation index. Measurements performed at rest may underestimate the haemodynamic effects of liquorice ingestion, as enhanced central wave reflection and reduced chronotropic response were especially observed in the upright position.

Haemodynamic Influences of Bisoprolol in Hypertensive Middle-Aged Men: A Double-Blind, Randomized, Placebo-Controlled Cross-Over Study.

Treatment with beta-blockers appears to show inferior reduction in central versus peripheral blood pressure. We aimed to examine simultaneous changes in central and peripheral blood pressure, vascular resistance, cardiac function and arterial stiffness during beta-blockade. Haemodynamics were investigated after 3 weeks of bisoprolol treatment (5 mg/day) in a double-blind, randomized, placebo-controlled cross-over trial in never-treated 16 Caucasian males with grade I-II primary hypertension using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Bisoprolol decreased radial (134/80 versus 144/89 mmHg) and aortic blood pressure (122/80 versus 130/90 mmHg) and heart rate (57 versus 68 beats/min) when compared with placebo (p < 0.05 for all). Ejection duration (336 versus 316 ms) and stroke volume (109 versus 98 ml) were increased (p < 0.01 for all), while cardiac output was not significantly changed (6.2 versus 6.6 l/min). Bisoprolol decreased pulse wave velocity (7.8 versus 8.9 m/s, p < 0.001), but after adjustment for blood pressure, the decrease was not significant (8.16 versus 8.52 m/s, p = 0.464). The treatment reduced pulse pressure amplification from central to peripheral circulation (30 versus 38%, p = 0.002). No differences were observed in systemic vascular resistance, augmentation index, aortic characteristic impedance or total arterial stiffness after bisoprolol versus placebo. Bisoprolol decreased central and peripheral blood pressure and pulse wave velocity in male individuals with grade I to grade II hypertension. The decrease in pulse wave velocity was related to the antihypertensive effect. Reduced pulse pressure amplification indicates that peripheral blood pressure was reduced more efficiently than central blood pressure.

Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication.

BACKGROUND: Augmentation index, a marker of central wave reflection, is influenced by age, sex, height, blood pressure, heart rate, and arterial stiffness. However, the detailed haemodynamic determinants of augmentation index, and their relations, remain uncertain. We examined the association of augmentation index with vascular resistance and other haemodynamic and non-haemodynamic factors. METHODS: Background information, laboratory values, and haemodynamics of 488 subjects (239 men, 249 women) without antihypertensive medication were obtained. Indices of central wave reflection, systemic vascular resistance, cardiac function, and pulse wave velocity were measured using continuous radial pulse wave analysis and whole-body impedance cardiography. RESULTS: In a regression model including only haemodynamic variables, augmentation index in males and female subjects, respectively, was associated with systemic vascular resistance (ß = 0.425, ß = 0.336), pulse wave velocity (ß = 0.409, ß = 0.400) (P < 0.001 for all), stroke volume (ß = 0.256, ß = 0.278) (P = 0.001 for both) and heart rate (ß = -0.150, ß = -0.156) (P = 0.049 and P = 0.036). When age, height, weight, smoking habits, and laboratory values were included in the regression model, the most significant explanatory variables for augmentation index in males and females, respectively, were age (ß = 0.577, ß = 0.557) and systemic vascular resistance (ß = 0.437, ß = 0.295) (P < 0.001 for all). In the final regression model, pulse wave velocity was not a significant explanatory variable for augmentation index, probably due to the high correlation of this variable with age (Spearman's correlation ≥0.617). CONCLUSION: Augmentation index is strongly associated with systemic vascular resistance in addition to arterial stiffness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01742702 .

Increased Cardiac Workload in the Upright Posture in Men: Noninvasive Hemodynamics in Men Versus Women.

BACKGROUND: Men and women differ in the risk of cardiovascular disease, but the underlying mechanisms are not completely understood. We examined possible sex-related differences in supine and upright cardiovascular regulation. METHODS AND RESULTS: Hemodynamics were recorded from 167 men and 167 women of matching age (≈45 years) and body mass index (≈26.5) during passive head-up tilt. None had diabetes mellitus or cardiovascular disease other than hypertension or used antihypertensive medication. Whole-body impedance cardiography, tonometric radial blood pressure, and heart rate variability were analyzed. Results were adjusted for height, smoking, alcohol intake, mean arterial pressure, plasma lipids, and glucose. Supine hemodynamic differences were minor: Men had lower heart rate (-4%) and higher stroke index (+7.5%) than women (P<0.05 for both). Upright systemic vascular resistance was lower (-10%), but stroke index (+15%), cardiac index (+16%), and left cardiac work were clearly higher (+20%) in men than in women (P<0.001 for all). Corresponding results were observed in a subgroup of men and postmenopausal women (n=76, aged >55 years). Heart rate variability analyses showed higher low:high frequency ratios in supine (P<0.001) and upright (P=0.003) positions in men. CONCLUSIONS: The foremost difference in cardiovascular regulation between sexes was higher upright hemodynamic workload for the heart in men, a finding not explained by known cardiovascular risk factors or hormonal differences before menopause. Heart rate variability analyses indicated higher sympathovagal balance in men regardless of body position. The deviations in upright hemodynamics could play a role in the differences in cardiovascular risk between men and women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01742702.

The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers.

BACKGROUND: In a cross-sectional study we examined whether the haemodynamic response to upright posture could be divided into different functional phenotypes, and whether the observed phenotypes were associated with known determinants of cardiovascular risk. METHODS: Volunteers (n = 470) without medication with cardiovascular effects were examined using radial pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis. Based on the passive head-up tilt induced changes in systemic vascular resistance and cardiac output, the principal determinants of blood pressure, a cluster analysis was performed. RESULTS: The haemodynamic response could be clustered into 3 categories: upright increase in vascular resistance and decrease in cardiac output were greatest in the first (+45 % and -27 %, respectively), smallest in the second (+2 % and -2 %, respectively), and intermediate (+22 % and -13 %, respectively) in the third group. These groups were named as 'constrictor' (n = 109), 'sustainer' (n = 222), and 'intermediate' (n = 139) phenotypes, respectively. The sustainers were characterized by male predominance, higher body mass index, blood pressure, and also by higher pulse wave velocity, an index of large arterial stiffness, than the other groups (p < 0.01 for all). Heart rate variability analysis showed higher supine and upright low frequency/high frequency (LF/HF) ratio in the sustainers than constrictors, indicating increased sympathovagal balance. Upright LF/HF ratio was also higher in the sustainer than intermediate group. In multivariate analysis, independent explanatory factors for higher pulse wave velocity were the sustainer (p < 0.022) and intermediate phenotypes (p < 0.046), age (p < 0.001), body mass index (p < 0.001), and hypertension (p < 0.001). CONCLUSIONS: The response to upright posture could be clustered to 3 functional phenotypes. The sustainer phenotype, with smallest upright decrease in cardiac output and highest sympathovagal balance, was independently associated with increased large arterial stiffness. These results indicate an association of the functional haemodynamic phenotype with an acknowledged marker of cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT01742702.

Effect of fermented milk product containing lactotripeptides and plant sterol esters on haemodynamics in subjects with the metabolic syndrome--a randomised, double-blind, placebo-controlled study.

We investigated the effects of fermented milk product containing isoleucine-proline-proline, valine-proline-proline and plant sterol esters (Pse) on plasma lipids, blood pressure (BP) and its determinants systemic vascular resistance and cardiac output. In a randomised, double-blind, placebo-controlled study, 104 subjects with the metabolic syndrome (MetS) were allocated to three groups in order to receive fermented milk product containing (1) 5 mg/d lactotripeptides (LTP) and 2 g/d plant sterols; (2) 25 mg/d LTP and 2 g/d plant sterols; (3) placebo for 12 weeks. Plasma lipids and home BP were monitored. Haemodynamics were examined in a laboratory using radial pulse wave analysis and whole-body impedance cardiography in the supine position and during orthostatic challenge. There were no differences between the effects of the two treatments and placebo on the measurements of BP at home or on BP, systemic vascular resistance index and cardiac index in the laboratory, neither in the supine nor in the upright position. The changes in plasma LDL-cholesterol concentration were - 0.1 (95% CI - 0.3, 0.1 and - 0.3, 0.0) mmol/l in the 5 and 25 mg/d LTP groups, respectively, and +0.1 (95% CI - 0.1, 0.3) mmol/l during placebo (P= 0.024). Both at baseline and at week 12, the increase in systemic vascular resistance during head-up tilt was lower in the 25 mg/d LTP group than in the 5 mg/d LTP group (P< 0.01), showing persistent differences in cardiovascular regulation between these groups. In subjects with the MetS, intake of LTP and Pse in fermented milk product showed a lipid-lowering effect of borderline significance, while no antihypertensive effect was observed at home or in the laboratory.

Lower glomerular filtration rate is associated with higher systemic vascular resistance in patients without prevalent kidney disease.

The authors examined the association between estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation, and hemodynamics in 556 normotensive or never-treated hypertensive patients without kidney disease (mean age, 46 years). Hemodynamic variables were recorded using pulse wave analysis and whole-body impedance cardiography. The mean eGFR was 98 mL/min/1.73 m(2) (range, 64-145 mL/min/1.73 m(2) and one third of the patients had values below 92, while none had proteinuria. In linear regression analyses adjusted for differences in age, weight:height ratio, low-density lipoprotein cholesterol, and sex, significant associations were found between lower eGFR and higher systolic (P=.001) and diastolic blood pressure (P<.001) and higher systemic vascular resistance (P=.001). There was no association between eGFR and cardiac output or extracellular volume. In the absence of clinical kidney disease, lower eGFR was associated with higher blood pressure and systemic vascular resistance. Therefore, early impairment in kidney function may be involved in the pathogenesis of essential hypertension.

Daily liquorice consumption for two weeks increases augmentation index and central systolic and diastolic blood pressure.

BACKGROUND: Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alterations are unknown. We studied haemodynamic changes induced by liquorice consumption in 20 subjects versus 30 controls with average blood pressures of 120/68 and 116/64 mmHg, respectively. METHODS: Haemodynamic variables were measured in supine position before and after two weeks of liquorice consumption (daily glycyrrhizin dose 290-370 mg) with tonometric recording of radial blood pressure, pulse wave analysis, and whole-body impedance cardiography. Thirty age-matched healthy subjects maintaining their normal diet were studied as controls. RESULTS: Two weeks of liquorice ingestion elevated peripheral and central systolic and diastolic blood pressure (by 7/4 and 8/4 mmHg, 95% confidence intervals [CI] 2-11/1-8 and 3-13/1-8, respectively, P<0.05), and increased extracellular volume by 0.5 litres (P<0.05 versus controls). Also augmentation index adjusted to heart rate 75/min (from 7% to 11%, 95% CI for change 0.3-7.5, P<0.05) and aortic pulse pressure (by 4 mmHg, 95% CI 1-7, P<0.05) were elevated indicating increased wave reflection from the periphery. In contrast, peripheral (-3/-0.3 mmHg) and central blood pressure (-2/-0.5 mmHg), aortic pulse pressure (-1 mmHg), and augmentation index adjusted to heart rate 75/min (from 9% to 7%) decreased numerically but not statistically significantly without changes in extracellular volume in the control group. Heart rate, systemic vascular resistance, cardiac output, and pulse wave velocity did not differ between the groups. CONCLUSIONS: Two weeks of daily liquorice consumption increased extracellular volume, amplified pressure wave reflection from the periphery, and elevated central systolic and diastolic blood pressure. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT 2006-002065-39 ClinicalTrials.gov NCT01742702.

Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects.

BACKGROUND: High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt. METHODS: Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20-72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles. RESULTS: Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright. CONCLUSIONS: Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.

Metabolic syndrome may be associated with increased arterial stiffness even in the absence of hypertension: a study in 84 cases and 82 controls.

OBJECTIVE: To evaluate the hemodynamic characteristics of metabolic syndrome (MetS) in the absence and presence of hypertension. MATERIALS/METHODS: Altogether 166 subjects without previously diagnosed cardiovascular disease, diabetes, or antihypertensive medication, were allocated to four groups: control, hypertension only, MetS without hypertension, and MetS with hypertension (mean age 44-46 years). Cut-point for hypertension was blood pressure ≥140/90 mmHg. Other criteria of MetS were as defined by Alberti et al. 2009. Hemodynamic variables were measured using whole-body impedance cardiography and pulse wave analysis. RESULTS: Pulse wave velocity was higher in hypertensive and normotensive subjects with MetS than controls (p<0.05), and in the hypertensive MetS group than subjects with hypertension only (p<0.05). Aortic pulse pressure was higher in the two hypertensive groups than the two normotensive groups (p<0.05). Systemic vascular resistance index was higher in the hypertensive than normotensive MetS group (p<0.05), and in the group with hypertension alone than in controls (p<0.05). Heart rate was higher in the hypertensive Mets group than in controls and subjects with hypertension only (p<0.05). Cardiac index did not differ, while stroke index was lower in both groups with MetS than groups without MetS. Augmentation pressure was higher in the hypertensive MetS group than in controls and normotensive MetS group (p<0.05). CONCLUSIONS: Pulse wave velocity, an acknowledged marker of arterial stiffness, was associated with MetS even in the absence of hypertension. This emphasizes the importance of the prevention and treatment of MetS.

Hemodynamic alterations in hypertensive patients at rest and during passive head-up tilt.

OBJECTIVE: Hypertension is characterized by increased vascular resistance and arterial stiffness, but information about upright hemodynamics is scarce. We compared hemodynamics in hypertensive versus normotensive patients at rest and during passive head-up tilt. METHODS: Volunteers (n = 387, 19-72 years) without antihypertensive medication were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Seated office blood pressure was 4/10  mmHg (systolic/diastolic) higher than average supine values during hemodynamic measurements. As there is no accepted cut-off for hypertension during tilt-table tests, supine level at least 135/85  mmHg defined hypertension (n = 155) versus normotension (n = 232). Age, BMI, and proportion of men were higher among hypertensives (49 vs. 42 years, 28 vs. 25, 55 vs. 38%, respectively), and analyses were adjusted for these differences. RESULTS: Both at rest and during head-up tilt radial and aortic blood pressure and pulse pressure, cardiac index (CI) and work, systemic vascular resistance (SVR), and augmentation pressure were higher in hypertensive patients (P < 0.05 for all). Adjusted linear regression analyses showed that during passive head-up tilt aortic SBP and pulse pressure, stroke index, and left cardiac work index decreased less; heart rate increased less; and aortic DBP and SVR increased more in hypertensive patients (P < 0.05 for all); whereas reduction in CI and augmentation index did not differ between the groups. CONCLUSION: Not only supine hemodynamics, but also responses to head-up tilt differed between normotensive and hypertensive patients, indicating functional alterations beyond increased vascular resistance and higher arterial stiffness in hypertension.

Supine and upright haemodynamic effects of sublingual nitroglycerin and inhaled salbutamol: a double-blind, placebo-controlled, randomized study.

OBJECTIVES: Pulse wave analysis is widely applied to measure the haemodynamic effects of nitroglycerin and salbutamol as an endothelium-independent and endothelium-dependent vasodilator, respectively. The recordings are usually performed in supine position from 10 to 20 successive heartbeats without simultaneous measurement of vascular resistance and cardiac function. Our objective was to examine the effects of nitroglycerin and salbutamol on central haemodynamics, arterial stiffness, cardiac function, and vascular resistance in supine and upright positions. METHODS: A placebo-controlled, randomized and double-blinded passive head-up tilt protocol was performed after sublingual nitroglycerin (0.25 mg) or inhaled salbutamol (400 µg) in 35 healthy volunteers. Continuous tonometric pulse wave analysis, whole-body impedance cardiography, and plethysmographic finger blood pressure recordings were applied. RESULTS: Nitroglycerin decreased aortic and finger blood pressure, radial DBP, vascular resistance, augmentation index and pulse wave velocity, and increased heart rate, cardiac index, stroke index and aortic reflection time (P < 0.030 for all). Salbutamol moderately decreased radial and aortic blood pressure and finger DBP, augmentation index and vascular resistance, but increased heart rate and cardiac index (P < 0.030 for all). Almost all of the strong haemodynamic effects of nitroglycerin were emphasized during the head-up tilt, whereas the effects of salbutamol on heart rate and cardiac index were more pronounced in the supine position. CONCLUSION: The haemodynamic changes induced by nitroglycerin and salbutamol were dependent on body position: the effects of nitroglycerin were accentuated during the head-up tilt, whereas those of salbutamol were more evident in the supine position.

Reduced systemic vascular resistance in healthy volunteers with presyncopal symptoms during a nitrate-stimulated tilt-table test.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a nitroglycerin-stimulated tilt-table test. WHAT THIS STUDY ADDS: A major decrease in systemic vascular resistance was documented in subjects with presyncope during 0.25 mg nitroglycerin-stimulated tilt-table test, in the absence of changes in cardiac output. These findings indicated that even a small dose of nitroglycerin significantly decreased arterial resistance and cardiac afterload. AIMS The mechanism of nitrate-induced syncope remains controversial. We examined the haemodynamic changes in healthy volunteers during nitroglycerin-stimulated tilt-table test. METHODS: Continuous radial pulse wave analysis, whole-body impedance cardiography and plethysmographic finger blood pressure were recorded in a supine position and during head-up tilt in 21 subjects with presyncopal symptoms (6 male/15 female, age 43 ± 3 years) after 0.25 mg sublingual nitroglycerin and 21 control subjects (6 male/15 female, age 43 ± 2 years). The drug was administered in the supine position and a passive head-up tilt followed 5 min later. Additionally, nitroglycerin was only administered during head-up tilt in 19 subjects and the haemodynamics were recorded. RESULTS: Supine and upright haemodynamics were similar before nitroglycerin administration in the two groups. During the nitroglycerin-stimulated tilt test, aortic and radial mean blood pressure decreased significantly more in the presyncope group when compared with the controls (P= 0.0006 and P= 0.0004, respectively). The decreases in systemic vascular resistance (P= 0.0008) and heart rate (P= 0.002), and increase in aortic reflection time (P= 0.0002) were greater in the presyncope group, while the change in cardiac index was not different between the groups (P= 0.14). If nitroglycerin was administered during the upright tilt and not in supine position, the haemodynamic changes were quite corresponding. CONCLUSIONS: Presyncopal symptoms during nitrate-stimulated tilt test were explained by decreased systemic vascular resistance and increased aortic reflection time, while cardiac output remained unchanged. These findings indicated reduced arterial resistance in nitroglycerin-induced presyncope.

Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin.

AIMS: To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS: Continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head-up tilt were recorded in nine healthy subjects. Data were captured before and after L-arginine (10 mg mg(-1) min(-1)) or saline infusion, salbutamol (400 microg) or placebo inhalation, and sublingual nitroglycerin (0.25 mg) or placebo resoriblet. RESULTS: The results of all measurements were comparable before drug administration. The effects of inhaled salbutamol were apparent in the supine position: systemic vascular resistance (-9.2 +/- 2.6%) and augmentation index (-4.0 +/- 1.5%) decreased, and heart rate (8.6 +/- 2.5%) and cardiac output (8.8 +/- 3.1%) increased. L-arginine had no clear effects on supine haemodynamics, but during head-up tilt blood pressure was moderately decreased and reduction in aortic reflection time prevented, indicating improved large arterial compliance. Nitroglycerin reduced supine vascular resistance (-6.7 +/- 1.8%) and augmentation index (-7.4 +/- 1.6%), and increased cardiac output (+9.2 +/- 2.7%). During head-up tilt, nitroglycerin increased cardiac output (+10.6 +/- 5.6%) and heart rate (+40 +/- 7.5%), decreased vascular resistance (-7.8 +/- 5.8%) and augmentation index (-18.7 +/- 3.2%), and prevented the decrease in aortic reflection time. CONCLUSIONS: Inhaled salbutamol predominantly changed supine haemodynamics, whereas the moderate effects of L-arginine were observed during the head-up tilt. In contrast, small doses of nitroglycerin induced major changes in haemodynamics both supine and during the head-up tilt. Altogether, these results emphasize the importance of haemodynamic measurements in both the supine and upright positions.

Ageing and cardiovascular responses to head-up tilt in healthy subjects.

OBJECTIVE: Ageing is associated with increased postural blood pressure changes and attenuated cardiovascular reactivity. As the background of these changes remains uncertain, we examined arterial stiffness, cardiac function and vascular resistance in healthy subjects in supine position and during orthostatic challenge. METHODS: Haemodynamics of 179 normotensive subjects (109 female and 70 male, 21-59 years) were examined using continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic finger blood pressures. RESULTS: Both in supine position and during head-up tilt central and peripheral blood pressure and augmentation index (amplitude of the reflected pressure wave divided by pulse pressure) increased, and time of pulse wave reflection decreased with age. Supine pulse wave velocity progressively increased with age. There were only minor differences in supine and upright systemic vascular resistance, cardiac index, stroke index, and heart rate that were not systematically related to age. In regression analysis, the explanatory factors for a more pronounced decrease in central systolic blood pressure during the head-up tilt were in the age of 50-59 years, higher baseline pulse wave velocity and central systolic BP. None of the changes in other haemodynamic variables during tilt were related to age. CONCLUSION: As no systematic age-related differences were observed in cardiac function or vascular resistance, these results support the view that progressive reduction of large arterial compliance contributes to the exaggerated age-related decrease in central systolic blood pressure in response to head-up tilt.

Hyperuricemia, oxidative stress, and carotid artery tone in experimental renal insufficiency.

BACKGROUND: Hyperuricemia may play a role in the pathogenesis of cardiovascular disease, but uric acid is also a significant antioxidant. We investigated the effects of oxonic acid-induced hyperuricemia on carotid artery tone in experimental renal insufficiency. METHODS: Three weeks after 5/6 nephrectomy (NX) or Sham operation, male Sprague-Dawley rats were allocated to 2.0% oxonic acid or control diet for 9 weeks. Blood pressure was monitored using tail cuff, isolated arterial rings were examined using myographs, and blood and urine samples were taken, as appropriate. Oxidative stress and antioxidant status were evaluated by measuring urinary 8-isoprostaglandin F(2 alpha) (8-iso-PGF(2 alpha)) excretion and plasma total peroxyl radical-trapping capacity (TRAP), respectively. RESULTS: Plasma creatinine was elevated twofold in NX rats, but neither NX nor oxonic acid diet influenced blood pressure. Urinary 8-iso-PGF(2 alpha) excretion was increased over 2.5-fold in NX rats on control diet. Oxonic acid diet increased plasma uric acid 2-3-fold, TRAP 1.5-fold, and reduced urinary 8-iso-PGF(2 alpha) excretion by 60-90%. Carotid vasorelaxation to acetylcholine in vitro, which could be abolished by nitric oxide (NO) synthase inhibition, was reduced following NX, whereas maximal response to acetylcholine was augmented in hyperuricemic NX rats. Vasorelaxation to nitroprusside was impaired in NX rats, whereas oxonic acid diet increased sensitivity also to nitroprusside in NX rats. CONCLUSIONS: Oxonic acid-induced hyperuricemia reduced oxidative stress in vivo, as evaluated using urinary 8-iso-PGF(2 alpha) excretion, increased plasma TRAP, and improved NO-mediated vasorelaxation in the carotid artery in experimental renal insufficiency.