A stochastic delay differential model of cerebral autoregulation

Mathematical models of the cardiovascular system and of cerebral autoregulation (CAR) have been employed for several years in order to describe the time course of pressures and flows changes subsequent to postural changes. The assessment of the degree of efficiency of cerebral auto regulation has indeed importance in the prognosis of such conditions as cerebro-vascular accidents or Alzheimer. In the quest for a simple but realistic mathematical description of cardiovascular control, which may be fitted onto non-invasive experimental observations after postural changes, the present work proposes a first version of an empirical Stochastic Delay Differential Equations (SDDEs) model. The model consists of a total of four SDDEs and two ancillary algebraic equations, incorporates four distinct delayed controls from the brain onto different components of the circulation, and is able to accurately capture the time course of mean arterial pressure and cerebral blood flow velocity signals, reproducing observed auto-correlated error around the expected drift

Heart rate variability in patients with cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Cirrhosis is associated with abnormal autonomic function and regulation of cardiac rhythm. Measurement of heart rate variability (HRV) provides an accurate and non-invasive measurement of autonomic function as well as liver disease severity currently calculated using the MELD, UKELD, or Child-Pugh scores. This review assesses the methods employed for the measurement of HRV, and evaluates the alteration of HRV indices in cirrhosis, as well as their value in prognosis. METHOD: We undertook a systematic review using Medline, Embase and Pubmed databases in July 2020. Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias of included studies was assessed by a modified version of the Newcastle-Ottawa Scale. The studies descriptive were analysed and the standardized mean differences of HRV indices were pooled. RESULTS: Of the 247 studies generated from our search, 14 studies were included. One of the 14 studies was excluded from meta-analysis because it reported only median of HRV indices. The studies included have a low risk of bias, and include 583 patients with cirrhosis and 349 healthy controls. The HRV time and frequency domains were significantly lower in cirrhotic patients. Between-studies heterogeneity was high in most of the pooled studies (P<0.05). Further, HRV indices predict survival independent of the severity of liver disease as assessed by MELD. CONCLUSION: HRV is decreased in patients with cirrhosis compared with healthy matched controls. HRV correlated with severity of liver disease and independently predicted survival. There was considerable variation in the methods used for HRV analysis, and this impedes interpretation and clinical applicability. Based on the data analysed, SDNN (standard deviation of inter-beat intervals) and cSDNN (i.e. SDNN corrected for basal heart rate) are the most suitable indices for prognosis in patients with cirrhosis

Forehead laser doppler and transcranial doppler during simulated hypovolemia

The present study employed lower body negative pressure (LBNP), a rapidly titratable, safe and reversible means of inducing simulated hypovolemia, for a comparison of transcranial Doppler (TCD) ultrasound of the middle cerebral artery and laser Doppler (LD) flowmetry of the forehead microvasculature. With IRB approval, 9 healthy volunteers (26.3±2.7 years) were monitored continuously with EKG, noninvasive finger arterial blood pressure (BP), and TCD positioned at the transtemporal window. After a baseline (Base) period, subjects underwent rapid onset of LBNP to -70 mmHg over the course of 1 minute, followed by progressive declines of ~10 mmHg until lightheadedness or had a BP decline \u3e20% of baseline BP. Changes in the peak (systolic) and trough (diastolic) values with each heart beat were analyzed at Base, at approx. 30 seconds prior to the onset of lightheadedness (Presympt) and at onset of symptoms (Sympt). In the 6 subjects who subsequently became lightheaded, forehead LD flow decreased by 10.9±11.7% at Presympt (p=NS for interphase difference). It then decreased by an additional 20.4±18.7% with the onset of lightheadedness (p=0.035 for Presympt vs. Sympt). Peak TCD readings decreased by 29.3±9.7% from Base to the time of the Presympt measurement (p=0.001); they then increased by 4.1±12.9% with the onset of Sympt (p=NS). In the 2 subjects who remained asymptomatic, LD did not change significantly in the Presympt and Sympt phases where Sympt was the time when the study was terminated because the BP cutoff was reached. In these asymptomatic subjects, the TCD flow velocity declined progressively. The present findings suggest that monitoring of the microvasculature in the distribution of the carotid arteries provides a better indication of changes in perfusion associated with lightheadedness than measurement of velocity at the middle cerebral artery. The discordance between LD and TCD is consistent with autoregulatory mechanisms at the level of the forehead microvasculature that have previously been reported in the context of systemic administration of phenylephrine

Heart rate and blood pressure variability : association with white matter lesions and cognitive function following stroke

Dementia presents a significant health care burden. Older post-stroke patients suffer high rates of dementia. Subcortical ischaemia may be an important mechanism of cognitive decline, particularly in older patients with cerebrovascular disease. It is hypothesised that abnormal heart rate and blood pressure variability will increase white matter lesion volume through hypoperfusion. This may lead to a subcortical pattern of cognitive decline characterised for example by deficits in attention and concentration. Stroke patients aged > 75 years and free of dementia had a series of cardiovascular autonomic, brain imaging and neuropsychometric investigations performed more than three months following incident stroke. Annual neuropsychometric assessment included CAMCOG score and measures of reaction time and concentration using a series of visual and numerical tasks presented on computer (Cognitive Drug Research Assessment System). Autonomic function is impaired in older stroke patients in the long term after stroke. These deficits are weakly associated with cross-sectional measures of sub-cortical performance but do not predict subsequent decline in cognitive function. Twenty-four hour blood pressure variability is associated with white matter disease and excessive nocturnal dipping is associated with impaired cognitive function. Again blood pressure variability does not help predict subsequent change in white matter lesion burden or cognitive function. This study provides limited support for the hypoperfusion theory of post-stroke cognitive impairment. However it does not indicate a role for heart rate and blood pressure variability in the mechanism of increasing white matter disease or decline in cognition in the two years following stroke.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Review and classification of variability analysis techniques with clinical applications

Analysis of patterns of variation of time-series, termed variability analysis, represents a rapidly evolving discipline with increasing applications in different fields of science. In medicine and in particular critical care, efforts have focussed on evaluating the clinical utility of variability. However, the growth and complexity of techniques applicable to this field have made interpretation and understanding of variability more challenging. Our objective is to provide an updated review of variability analysis techniques suitable for clinical applications. We review more than 70 variability techniques, providing for each technique a brief description of the underlying theory and assumptions, together with a summary of clinical applications. We propose a revised classification for the domains of variability techniques, which include statistical, geometric, energetic, informational, and invariant. We discuss the process of calculation, often necessitating a mathematical transform of the time-series. Our aims are to summarize a broad literature, promote a shared vocabulary that would improve the exchange of ideas, and the analyses of the results between different studies. We conclude with challenges for the evolving science of variability analysis

Clinical pathophysiology: the essentials

ПОСОБИЯФИЗИОЛОГИЯПАТОЛОГИЯМЕДИЦИНА КЛИНИЧЕСКАЯСЕРДЕЧНО-СОСУДИСТАЯ СИСТЕМА /ПАТОФИЗИОЛОГИЯДЫХАТЕЛЬНАЯ СИСТЕМА /ПАТОФИЗИОЛОГИЯЖЕЛУДОЧНО-КИШЕЧНЫЙ ТРАКТ /ПАТОФИЗИОЛОГИЯПЕЧЕНЬ /ПАТОФИЗИОЛОГИЯПОЧКИ /ПАТОФИЗИОЛОГИЯЭНДОКРИННАЯ СИСТЕМА /ПАТОФИЗИОЛОГИЯНЕРВНАЯ СИСТЕМА /ПАТОФИЗИОЛОГИЯПАТОФИЗИОЛОГИЯИНОСТРАННЫЕ СТУДЕНТЫВ издании рассматриваются вопросы патофизиологии заболеваний основных систем организма, а также обсуждаются патофизиологические основы диагностики, профилактики и лечения заболеваний человека

Untersuchungen zum Einfluss der Antipsychotika auf die Endothelfunktion und das Autonome Nervensystem bei schizophrenen Patienten

Die Behandlung mit Antipsychotika stellt die leitliniengerechte Therapie der paranoiden Schizophrenie dar. Allerdings sollen sie einen negativen Einfluss auf das kardiovaskuläre Risikoprofil ausüben. Schizophrene Patienten haben im Vergleich zur gesunden Bevölkerung ein deutlich erhöhtes Mortalitätsrisiko. Bereits zum Zeitpunkt der ersten Krankheitsexazerbation können Faktoren des metabolischen Syndroms, eine endotheliale Dysfunktion sowie eine Fehlregulation des autonomen Nervensystems mit Überwiegen der sympathischen Aktivität nachgewiesen werden. Die endotheliale Dysfunktion gilt als frühzeitiger prognostischer Marker zur kardiovaskulären Risikostratifizierung. Zur Untersuchung des autonomen Nervensystems eignen sich die Herzratenvariabilität und Baroreflexsensitivität. Dabei stehen eine Verringerung der HRV oder BRS für eine reduzierte parasympathische Modulation und gelten als Risikofaktoren für arrhythmiebedingte kardiale Ereignisse. Ziel dieser Arbeit war es, den Einfluss der Antipsychotika auf die bereits bekannten Veränderungen zu untersuchen. Zur besseren Vergleichbarkeit erfolgten die Untersuchungen an der gleichen Patientengruppe (n = 20) zu zwei verschiedenen Zeitpunkten. Die 1. Messung erfolgte während der akuten Psychose und wurde unter neuroleptischer Medikation wiederholt. Die Ergebnisse wurden mit denen einer gesunden Kontrollgruppe verglichen. Während der akuten Psychose zeigte sich eine endotheliale Dysfunktion. Die HRV und BRS waren signifikant verringert, wodurch die Dysregulation des autonomen Nervensystems verdeutlicht werden kann. Unter der antipsychotischen Therapie verbesserte sich die Endothelfunktion signifikant im Vergleich zur 1. Messung. Hinsichtlich der BRS und HRV waren keine Veränderungen erkennbar. Die kurzfristige Antipsychotikatherapie führt zu keiner weiteren Verschlechterung des kardiovaskulären Risikos. Möglicherweise tragen die Antipsychotika über metabolische Folgen zur Erhöhung des kardiovaskulären Risikos bei

Principal component based system identification and its application to the study of cardiovascular regulation

Includes bibliographical references (p. 197-212).Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2004.(cont.) Our methods analyze the coupling between instantaneous lung volume and heart rate and, subsequently, derive representative indices of parasympathetic and sympathetic control based on physiological and experimental findings. The validity of each method is evaluated via experimental data collected following interventions with known effect on the parasympathetic or sympathetic control. With the above techniques, this thesis explores an important topic in the field of space medicine: effects of simulated microgravity on cardiac autonomic control and orthostatic intolerance (OI). Experimental data from a prolonged bed rest study (simulation of microgravity condition) are analyzed and the conclusions are: 1) prolonged bed rest may impair autonomic control of heart rate; 2) orthostatic intolerance after bed rest is associated with impaired sympathetic responsiveness; 3) there may be a pre-bed rest predisposition to the development of OI after bed rest. These findings may have significance for studying Earth-bound orthostatic hypotension as well as for designing effective countermeasures to post-flight OI. In addition, they also indicate the efficacy of our proposed methods for autonomic function quantification.System identification is an effective approach for the quantitative study of physiologic systems. It deals with the problem of building mathematical models based on observed data and enables a dynamical characterization of the underlying physiologic mechanisms specific to the individual being studied. In this thesis, we develop and validate a new linear time-invariant system identification approach which is based on a weighted-principal component regression (WPCR) method. An important feature of this approach is its asymptotic frequency-selective property in solving time-domain parametric system identification problems. Owing to this property, data-specific candidate models can be built by considering the dominant frequency components inherent in the input (and output) signals, which is advantageous when the signals are colored, as are most physiologic signals. The efficacy of this method in modeling open-loop and closed-loop systems is demonstrated with respect to simulated and experimental data. In conjunction with the WPCR-based system identification approach, we propose new methods to noninvasively quantify cardiac autonomic control. Such quantification is important in understanding basic pathophysiological mechanisms or in patient monitoring, treatment design and follow-up.by Xinshu Xiao.Ph.D