Small artery elasticity is decreased in patients with systemic lupus erythematosus without increased intima media thickness

Introduction: The objectives of this study were to determine small arterial elasticity (SAE) in systemic lupus erythematosus (SLE) and to investigate its relationship with intima media thickness (IMT), accumulation of advanced glycation end products (AGEs), endothelial activation and inflammation. Methods: Thirty SLE patients with inactive disease and 30 age- and sex-matched healthy controls were included. Twenty patients with essential hypertension (EH) served as positive control. SAE was assessed by pulse-wave analysis using tonometric recordings of the radial artery. IMT of the carotid arteries was measured by ultrasound. AGE accumulation was assessed with an AGE-reader. Endothelial activation markers and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay (ELISA). Results: SAE was decreased in SLE (P = 0.01) and further decreased in EH (P <0.01) compared to healthy controls. IMT was increased in EH (P <0.05), but not in SLE. AGE accumulation was increased in SLE (P <0.05) and further increased in EH (P <0.01) compared to healthy controls. Endothelial activation markers and CRP were increased in SLE but not in EH. SAE related to AGE accumulation (r = -0.370, P <0.05), CRP (r = -0.429, P <0.05) and creatinine clearance (r = 0.440, P <0.05), but not to IMT and endothelial activation markers. In multivariate analysis SLE was an independent predictor of SAE. Conclusions: SAE is decreased in SLE patients without increased IMT, independently of traditional cardiovascular risk factors. Longitudinal studies are needed to investigate whether SAE, endothelial activation and AGE accumulation are early markers for cardiovascular disease in SLE

Changes in hemodynamics associated with metabolic syndrome are more pronounced in women than in men

The increase in cardiovascular risk associated with metabolic syndrome (MS) seems higher in women than in men. We examined hemodynamics during head-up tilt in 252 men and 250 women without atherosclerosis, diabetes, or antihypertensive medication, mean age 48 years, using whole-body impedance cardiography and radial pulse wave analysis. MS was defined according to Alberti et al. 2009. Men and women with MS presented with corresponding elevations of systolic and diastolic blood pressure (10-14%, p ≤ 0.001) versus controls. Supine pulse wave velocity (16–17%, p publishedVersionPeer reviewe

The pulsating brain: A review of experimental and clinical studies of intracranial pulsatility

The maintenance of adequate blood flow to the brain is critical for normal brain function; cerebral blood flow, its regulation and the effect of alteration in this flow with disease have been studied extensively and are very well understood. This flow is not steady, however; the systolic increase in blood pressure over the cardiac cycle causes regular variations in blood flow into and throughout the brain that are synchronous with the heart beat. Because the brain is contained within the fixed skull, these pulsations in flow and pressure are in turn transferred into brain tissue and all of the fluids contained therein including cerebrospinal fluid. While intracranial pulsatility has not been a primary focus of the clinical community, considerable data have accrued over the last sixty years and new applications are emerging to this day. Investigators have found it a useful marker in certain diseases, particularly in hydrocephalus and traumatic brain injury where large changes in intracranial pressure and in the biomechanical properties of the brain can lead to significant changes in pressure and flow pulsatility. In this work, we review the history of intracranial pulsatility beginning with its discovery and early characterization, consider the specific technologies such as transcranial Doppler and phase contrast MRI used to assess various aspects of brain pulsations, and examine the experimental and clinical studies which have used pulsatility to better understand brain function in health and with disease

Cardiovascular autonomic control after spinal cord injury: Comprehensive investigations into classification and care

Over 86,000 Canadians live with the consequences of a spinal cord injury (SCI). Injury to spinal autonomic pathways can lead to profound cardiovascular autonomic dysfunction. Key areas of concern identified by individuals living with SCI relate to continence and cardiovascular dysfunction. Conditions that result from autonomic dysfunction, such as autonomic dysreflexia (sudden extreme hypertension) are of particular concern. This thesis examined the cardiovascular autonomic consequences of SCI and their relationship to bowel care, the most potent stimulus for dysreflexia, and a key factor that negatively impacts quality of life after SCI. To assess cardiovascular autonomic control, first a quantitative marker of autonomic dysfunction following SCI had to be identified. In Aim 1 (Chapter 3), cardiovascular dysfunction during, and beyond, the first year of injury (n=63) was assessed using a novel quantitative non-invasive marker of cardiovascular autonomic control. From here, a randomized double-blind placebo-controlled crossover clinical trial to determine the effect of topical afferent blockade (lidocaine) on dysreflexia severity during bowel care was conducted (n=13). Aim 2 (Chapter 4) provides evidence that, contrary to current clinical guidelines, topical lidocaine prolongs bowel care, worsens dysreflexia, and increases cardiovascular symptoms. Despite bowel care concerns, past research shows that individuals do not change bowel care practices, highlighting knowledge translation gaps concerning evidence-based bowel management strategies. To address this, in Aim 3 (Chapter 5), semi-structured interviews (n=13) were used to examine the barriers and facilitators to changing bowel care. The largest influences on changing bowel care and potentially relevant intervention options were identified. Finally, during dysreflexia profound sympathetic stimulation may increase risk for cardiac arrhythmia. Aim 4 (Chapter 6) evaluated susceptibility to arrhythmia in a rodent-model of SCI, the impact of the sympathomimetic drug dobutamine on arrhythmia risk, and the potential mitigating effect of exercise training. SCI increased susceptibility to cardiac arrhythmia, with dobutamine further increasing susceptibility in high-level SCI. Exercise training ameliorated markers of arrhythmia risk during dobutamine. The research conducted in this thesis uses a translational and patient-orientated approach to bridge the gap between physiological understanding and meaningful improvement in the clinical setting for individuals living with cardiovascular and continence implications of SCI

The Influence of Ultra-Endurance Exercise on the Cardiovascular and Related Physiological Systems

INTRODUCTION: There is currently limited longitudinal data investigating the performance and health-related influence of ultra-endurance training and participation. Cross-sectional investigations have highlighted a potential for those performing most exercise to be at an increased risk of cardiovascular events. If such risks occur, they are likely to be due to a combination of the stress provided through training and events together. PURPOSE: To assess the development of several physiological factors associated with exercise training and to gain a greater insight regarding the changes in cardiac electrical conductance from endurance training. A sub-study sought to investigate the short and longer-term influence of an iron-distance triathlon on indirect measures of arterial stiffness. METHOD: Part 1: Seventy-six previously recreationally active participants underwent a 6 month endurance training programme in preparation for an iron-distance triathlon, consisting of a 3.86km swim, 180.25km cycle, and a 42.2km run. Multiple assessments were performed at months 0, 2, 4 and 6; including submaximal and exhaustive cycling tests, anthropometric measurements and 12-lead ECG’s. Part 2: Eleven athletes from part 1 (TRI) and 10 recreational control participants (NOTRI) were assessed on 4 occasions with identical time intervals. Arterial stiffness and cardiovascular functional parameters were obtained 7 days prior (T1) to an iron-distance triathlon, 12–18 hours post-event, 7 days post-event, and 28 days post-event. RESULTS: Part 1: Cardiorespiratory fitness and performance parameters increased over the training period, irrespective of age, with greatest improvements from month 0–2 and the least improvements from month 4–6. Additionally, a progressive increase was observed in the frequency of both training-related and training-unrelated ECG findings. Part 2: A significant difference in central arterial stiffness was found between TRI and NOTRI 12–18 hours post-event and 7 days post-event but not prior to or 28 days post-event. No differences were observed between groups for peripheral stiffness at any time-point. Additionally, no time effect was observed when the TRI group were treated separately. CONCLUSION: Training caused significant improvements to fitness related physiological factors. In a minority of individuals, endurance training induced bioelectrical patterns of what is currently referred to as abnormal criteria, which may reflect a normal change to what was previously thought of as abnormal findings or, alternatively, be pathological manifestations in previously healthy individuals. Part 2 of this study showed a delayed central arterial stiffening may occur one day and one week following a single day ultra-endurance event. Importantly, all measurements were found to be similar one month post-event; implying only a transient exercise-induced elevation to arterial stiffness

Comparison of Non-Invasive Peripheral Vascular Function to Invasive Measures of Coronary Function in Patients with Suspected Coronary Microvascular Dysfunction

This thesis examined whether reactive hyperemia peripheral arterial tonometry (RH-PAT) and flow-mediated dilation (FMD), non-invasive measures of peripheral endothelial function, are associated with coronary microvascular function following multiple pharmacological stimuli in patients with suspected coronary microvascular dysfunction (CMD). Patients with suspected CMD completed peripheral vascular assessments using concurrent RH-PAT and FMD, while coronary microvascular function was measured using the index of microvascular resistance (IMR) and the coronary flow reserve (CFR) during endothelial independent (adenosine), endothelial-dependent (acetylcholine), and sympathetically-mediated (dobutamine) hyperemia. Any abnormality in the IMR and/or CFR during the adenosine and/or acetylcholine trials defined patients with CMD. RH-PAT and FMD were attenuated in patients with CMD (P<0.05). RH-PAT was correlated with the dobutamine IMR and CFR (P<0.05), while FMD was correlated with the adenosine (P<0.05) and acetylcholine IMRs (P<0.05), but not the CFRs. Therefore, this thesis suggests that both RH-PAT and FMD can identify patients with CMD in clinical settings

A proof of concept study for machine learning application to stenosis detection

This proof of concept (PoC) assesses the ability of machine learning (ML) classifiers to predict the presence of a stenosis in a three vessel arterial system consisting of the abdominal aorta bifurcating into the two common iliacs. A virtual patient database (VPD) is created using one-dimensional pulse wave propagation model of haemodynamics. Four different machine learning (ML) methods are used to train and test a series of classifiers—both binary and multiclass—to distinguish between healthy and unhealthy virtual patients (VPs) using different combinations of pressure and flow-rate measurements. It is found that the ML classifiers achieve specificities larger than 80% and sensitivities ranging from 50 to 75%. The most balanced classifier also achieves an area under the receiver operative characteristic curve of 0.75, outperforming approximately 20 methods used in clinical practice, and thus placing the method as moderately accurate. Other important observations from this study are that (i) few measurements can provide similar classification accuracies compared to the case when more/all the measurements are used; (ii) some measurements are more informative than others for classification; and (iii) a modification of standard methods can result in detection of not only the presence of stenosis, but also the stenosed vessel

Whole body impedance cardiography and continuous pulse wave analysis in the measurement of human haemodynamics during passive head-up tilt

Kohonnut verenpaine on merkittävä kansanterveydellinen ongelma, ja jopa 70 % verenpainepotilaista ei saavuta hoitotavoitteita lääkehoidosta huolimatta. Verenpainetason säätelyyn osallistuu hyvin moni rakenteellinen ja toiminnallinen tekijä, mutta potilastyössä tyydytään kuitenkin usein verenpaineen ja syketason määrittämiseen levossa. Myös muutoksia mm.verisuonten myötäävyydessä, ääreisverenkierron vastuksen säätelyssä, verisuonen sisäkerroksen eli endoteelin toiminnassa sekä rasituskoevasteissa on mahdollista todeta jo ennen tautitapahtumien ilmaantumista. Muutokset voivat olla potilaiden välillä hyvin erilaisia, vaikka verenpainetaso olisi samanlainen. Tutkimuksen tarkoituksena oli kehittää kliiniseen työhön soveltuva mittausmenetelmä, jonka avulla saadaan monipuolinen ja yksilöllinen käsitys sydän- ja verenkiertoelimistön toiminnasta. Mittaukset suoritettiin sekä makuulla että kallistuskokeen aikana koko kehon impedanssikardiografiaa, jatkuvaa pulssiaaltoanalyysiä ja pletysmografista sormiverenpaineen mittausta käyttäen. Samanaikaisesti mitattavia muuttujia olivat sormi-, ranne- ja aorttatason verenpaine, pulssiaallon heijastumisesta kertovat suureet, pulssiaallon etenemisnopeus, ääreisverenkierron vastus sekä sydämen isku- ja minuuttitilavuus. Tutkimuksessa selvitettiin kahden pääasiassa endoteelivälitteisen lääkeaineen, salbutamolin ja L-arginiinin, ja yhden endoteelista riippumattoman, nitroglyseriinin, aiheuttamia muutoksia. Lisäksi tutkittiin ikääntymiseen liittyviä sydän- ja verenkiertoelimistön muutoksia. Menetelmän kehittämiseen liittyvät mittaukset suoritettiin terveille vapaaehtoisille, ja lopuksi menetelmää testattiin metabolista oireyhtymää ja essentielliä verenpainetautia saitastavilla potilailla. Mittaukset olivat toistettavia sekä makuulla että kallistuskokeen aikana. Salbutamoli ja nitroglyseriini laskivat verenpainetta, ääreisvastusta ja vähensivät pulssiaallon takaisinheijastumista, sekä nostivat sykettä ja sydämen minuuttitilavuutta. Salbutamolin aiheuttamat muutokset korostuivat makuuasennossa, kun taas vaste nitroglyseriinille oli selvempi kallistuskokeen aikana. L-arginiini aiheutti verenpaineen laskun kallistuskokeen aikana. Osalla tutkimushenkilöistä havaitun nitroglyseriinin aiheuttaman presynkopeen (huimaus, verenpaineen lasku) aikana havaittiin selvästi vähentynyt ääreisverenkierron vastus. Valtimojäykkyys ja pulssiaallon takaisinheijastuminen lisääntyivät iän myötä, mutta ääreisvastus ja sydämen pumppaustoiminta eivät muuttuneet. Suurempi aorttatason verenpaineen lasku kallistuskokeessa liittyi korkeampaan ikään ja lisääntyneeseen valtimojäykkyyteen. Metabolista oireyhtymää sairastavilla potilailla oli korkeampi syketaso ja pulssiaallon etenemisnopeus kuin verenpainetautia sairastavilla, vaikka verenpainetaso ja ääreisvastus eivät eronneet merkittävästi. Tulos osoittaa, että tutkituilla potilasryhmillä on verenpainetasosta riippumattomia eroja verenkiertoelimistön rakenteessa ja toiminnassa. Mittausmenetelmä on kajoamaton ja toistettava, ja mahdollistaa entistä tarkemman sydän- ja verenkiertoelimistön toiminnan määrittämisen. Tulokset korostavat myös pystyasennossa suoritettavien mittausten tärkeyttä, koska lääkevasteet ja ikääntymiseen liittyvät muutokset olivat erilaisia makuulla ja kallistuskokeessa. Menetelmän avulla saatavat tulokset mahdollistavat mm. yksilöllisen hoidon kohdentamisen, mikä todennäköisesti johtaa parempiin hoitotuloksiin.Regulation of blood pressure is a complex interplay between several haemodynamic mechanisms, but only resting blood pressure and heart rate are commonly measured in clinical practice to determine a patient s haemodynamic status. However, the value of single blood pressure measurements as diagnostic tests has recently been questioned. In addition, changes in for example arterial compliance, endothelial function, or the regulation of vascular resistance can already be measured before clinical manifestations of cardiovascular disease. The aim of the present study was to test the repeatability and reproducibility of a comprehensive haemodynamic measurement protocol in both supine position and during head-up tilt. In addition, the effects on two largely endothelium-dependent agents, inhaled salbutamol and intravenous L-arginine, and one endothelium independent agent, sublingual nitroglycerin, were investigated, and the haemodynamic mechanism of nitrate-induced presyncope were examined. Moreover, the age-related haemodynamic changes, supine and upright, in normotensive subjects were clarified. Finally, the application was tested in patients with either essential hypertension or metabolic syndrome. Non-invasive haemodynamic measurements were performed by applying whole body impedance cardiography, continuous pulse wave analysis and plethysmographic finger blood pressure measurements in supine position and during head-up tilt. Thus, peripheral and central blood pressure, indices of pulse wave reflection, pulse wave velocity, vascular resistance, and cardiac function could be simultaneously assessed. Repeated measurements were performed to test the repeatability and reproducibility of the method, and to study the drug effects in a placebo-controlled manner. All study subjects, except for the subjects included in the testing of the method s clinical application, were normotensive and had no medication affecting cardiovascular status. The measurement protocol was repeatable and reproducible in both supine position and during head-up tilt. Inhaled salbutamol decreased blood pressure, vascular resistance and augmentation index, while heart rate and cardiac output were increased. Sublingual nitroglycerin clearly decreased blood pressure, vascular resistance, augmentation index and pulse wave velocity, and increased heart rate and cardiac output. Importantly, the haemodynamic effects of nitroglycerin were enhanced during the head-up tilt, while the salbutamol effects were more evident in the supine position. Intravenous L-arginine resulted in decreased blood pressure and increased aortic reflection time only during the tilt. During nitrate-induced presyncope, reduced vascular resistance was observed. Increasing age from 20 to 60 years was associated with increased arterial stiffness and wave reflection, while no changes were observed in cardiac function or vascular resistance. A more pronounced decrease in central systolic blood pressure in response to tilt was associated with increased age and arterial stiffness. Subjects with metabolic syndrome had higher heart rate and arterial stiffness than hypertensive subjects, despite similar elevation of blood pressure and vascular resistance. These results suggest more widespread changes in cardiovascular status than just elevated blood pressure in metabolic syndrome. In conclusion, the present measurement protocol enables a detailed characterization of patients haemodynamic profile, including the assessment of the role of the endothelium in vascular responsiveness. The divergent effects of research drugs in different postures, and the age-related changes in haemodynamic responsiveness to head-up tilt underlie the importance to study upright haemodynamics