Nocturnal Transcutaneous Carbon Dioxide and Early Changes in Atherosclerosis in Pre- and Postmenopausal Women

The risk of cardiovascular diseases and sleep-disordered breathing increases after menopause. This cross-sectional study focuses on overnight transcutaneous carbon dioxide (TcCO2) measurements and their power to predict changes in the early markers of cardiovascular and metabolic diseases. The endothelial function of the brachial artery, the intima-media thickness of the carotid artery, blood pressure, glycosylated hemoglobin A1C and plasma levels of cholesterols and triglycerides were used as markers of cardiovascular and metabolic diseases. The study subjects consisted of healthy premenopausal women of 46 years of age and postmenopausal women of 56 years of age. From wakefulness to sleep, the TcCO2 levels increased more in postmenopausal women than in premenopausal women. In estrogen-users the increase in TcCO2 levels was even more pronounced than in other postmenopausal women. From the dynamic behaviour of the nocturnal TcCO2 signal, several important features were detected. These TcCO2 features had a remarkable role in the prediction of endothelial dysfunction and thickening of the carotid wall in healthy premenopausal women. In addition, these TcCO2 features were linked with blood pressure, lipid profile and glucose balance in postmenopausal women. The nocturnal TcCO2 profile seems to contain significant information, which is associated with early changes in cardiovascular diseases in middle-aged women. TcCO2 might not only measure the tissue carbon dioxide levels, but the TcCO2 signal variation may also reflect peripheral vasodynamic events caused by increased sympathetic activity during sleep.Siirretty Doriast

Inhaled Oxygen as a Quantitative Intravascular MRI Contrast Agent

Increasing the fraction of inspired oxygen (FiO2) generates MR contrast by two distinct mechanisms: increased T2 from deoxyhemoglobin dilution in venous compartments (blood oxygenation level-dependent effect or BOLD) and reduced T­1 from paramagnetic molecular oxygen dissolved in blood plasma and tissues. Many research and clinical applications using hyperoxic contrast have recently emerged, including delineating ischemic stroke penumbra, oxygen delivery to tumors, and functional MRI data calibration. However, quantitative measurements using this contrast agent depend on the precise knowledge of its effects on the MR signal – of which there remain many crucial missing pieces. This thesis aims to obtain a more quantitative understanding of intravascular hyperoxic contrast in vivo, with the hope of increasing its precision and utility. Specifically, our work focuses on the following areas: (1) paramagnetic effects of molecular oxygen BOLD and arterial spin labeling (ASL) data, (2) degree and temporal characteristics of hyperoxia-induced reductions in cerebral blood flow (CBF), (3) use of oxygen in quantitative measurements of metabolism, and (4) biophysical mechanisms of hyperoxic T1 contrast. In Chapter 2, the artifactual influence of paramagnetic molecular oxygen on BOLD-modulated hyperoxic gas studies is characterized as a function of static field strength, and we show that optimum reduction in FiO2 mitigates this effect while maintaining BOLD contrast. Since ASL measurements are highly sensitive to arterial blood T­1 (T1a), the value of T1a in vivo is determined as a function of arterial oxygen partial pressure in Chapter 3. The effect of both the degree and duration of hyperoxic exposure on absolute CBF are quantified using simultaneous ASL and in vivo T1a measurements, as described in Chapter 4. In Chapter 5, hyperoxic gas calibration of BOLD/ASL data is used to measure cerebral oxygen metabolism in a hypermetabolic swine model, with our results comparing favorably to 17O2 measurements of absolute metabolism. In Chapter 6, a model to describe the relationship between CBF, oxygen consumption, and hyperoxic T1 reduction is developed, which allows for a more rigorous physiological interpretation of these data. Taken together, this work represents several important steps towards making hyperoxia a more quantitative MRI contrast agent for research and clinical applications

Feasibility of waveform capnography as a non-invasive monitoring tool during cardiopulmonary resuscitation

178 p.Sudden cardiac arrest (SCA) is one of the leading causes of death in the industrialized world and it includes the sudden cessation of circulation and consciousness, confirmed by the absence of pulse and breathing. Cardiopulmonary resuscitation (CPR) is one of the key interventions for patient survival after SCA, a life-saving procedure that combines chest compressions and ventilations to maintain a minimal oxygenated blood flow.To deliver oxygen, an adequate blood flow must be generated, by effective CPR, during the majority of the cardiac arrest time. Although monitoring the quality of CPR performed by rescuers during cardiac arrest has been a huge step forward in resuscitation science, in 2013, a consensus statement from the American Heart Association prioritized a new type of CPR quality monitoring focused on the physiological response of the patient instead of how the rescuer is doing.To that end, current resuscitation guidelines emphasize the use of waveform capnography during CPR for patient monitoring. Among several advantages such as ensure correct tube placement, one of its most important roles is to monitor ventilation rate, helping to avoid potentially harmful over-ventilation. In addition, waveform capnography would enable monitoring CPR quality, early detection of ROSC and determining patient prognosis. However, several studies have reported the appearance of fast oscillations superimposed on the capnogram, hereinafter CC-artifact, which may hinder a feasible use of waveform capnography during CPR. In addition to the possible lack of reliability, several factors need to be taken into account when interpreting ETCO2 measurements. Chest compressions and ventilation have opposing effects on ETCO2 levels. Chest compressions increase CO2 concentration, delivering CO2 from the tissues to the lungs, whilst ventilations remove CO2 from the lungs, decreasing ETCO2. Thus, ventilation rate acts as a significant confounding factor.This thesis analyzes the feasibility of waveform capnography as non-invasive monitoring tool of the physiological response of the patient to resuscitation efforts. A set of four intermediate goals was defined.First, we analyzed the incidence and morphology of the CC-artifact and assessed its negative influence in the detection of ventilations and in ventilation rate and ETCO2 measurement. Second, several artifact suppression techniques were used to improve ventilation detection and to enhance capnography waveform. Third, we applied a novel strategy to model the impact of ventilations and ventilation rate on the exhaled CO2 measured in out-of-hospital cardiac arrest capnograms, which could allow to measure the change in ETCO2 attributable to chest compressions by removing the influence of concurrent ventilations. Finally, we studied if the assessment of the ETCO2 trends during chest compressions pauses could allow to detect return of spontaneous circulation, a metric that could be useful as an adjunct to other decision tool

Applications of Hybrid Diffuse Optics for Clinical Management of Adults After Brain injury

Information about cerebral blood flow (CBF) is valuable for clinical management of patients after severe brain injury. Unfortunately, current modalities for monitoring brain are often limited by hurdles that include high cost, low throughput, exposure to ionizing radiation, probe invasiveness, and increased risk to critically ill patients when transportation out of their room or unit is required. A further limitation of current technologies is an inability to provide continuous bedside measurements that are often desirable for unstable patients. Here we explore the clinical utility of diffuse correlation spectroscopy (DCS) as an alternative approach for bedside CBF monitoring. DCS uses the rapid intensity fluctuations of near-infrared light to derive a continuous measure of changes in blood flow without ionizing radiation or invasive probing. Concurrently, we employ another optical technique, called diffuse optical spectroscopy (DOS), to derive changes in cerebral oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) concentrations. Our clinical studies integrate DCS with DOS into a single hybrid instrument that simultaneously monitors CBF and HbO2/Hb in the injured adult brain. The first parts of this dissertation present the motivations for monitoring blood flow in injured brain, as well as the theory underlying diffuse optics technology. The next section elaborates on details of the hybrid instrumentation. The final chapters describe four human subject studies carried out with these methods. Each of these studies investigates an aspect of the potential of the hybrid monitor in clinical applications involving adult brain. The studies include: (1) validation of DCS-measured CBF against xenon-enhanced computed tomography in brain-injured adults; (2) a study of the effects of age and gender on posture-change-induced CBF variation in healthy subjects; (3) a study of the efficacy of DCS/DOS for monitoring neurocritical care patients during various medical interventions such as head-of-bed manipulation and induced hyperoxia; and (4) a first feasibility study for using DCS to study hemodynamics at high altitudes. The work presented in this dissertation thus further develops DCS/DOS technology and demonstrates its utility for monitoring the injured adult brain. It demonstrates the promise of this new clinical tool to help neurocritical care clinicians make more informed decisions and thereby improve patient outcome

EXERCISE-INDUCED CEREBROVASULAR RESPONSIVENESS AND BRAIN AGING MARKERS

At the interface of heart function and brain function is cerebrovascular function. The hundreds of miles of cerebrovasculature within our compact skulls exists to assure delivery of vital life substrates to brain tissue. A healthy cerebrovasculature is important to aging, as evidenced in age-related afflictions, including stroke and dementias. Cerebrovascular function is of tremendous interest to numerous fields, including, but not limited to, gerontology, physical therapy, rehabilitation medicine, psychology, neurology, and neurosurgery. Although we have made substantial advancements in understanding the aging brain, there are unanswered questions regarding cerebrovascular function which could ultimately impact our understanding of brain aging. This body of work addresses gaps regarding the role of cerebrovascular function in the aging brain, and it has potential clinical implications regarding cerebrovascular dysfunction in stroke and dementias. The aim of this work was to elucidate the links between resting and exercise-induced cerebrovascular function and three markers of brain aging: executive function, brain structural integrity, and β-amyloid, a cellular hallmark of Alzheimer’s disease pathology. Our analyses of exercise-induced cerebrovascular functions revealed links between cerebrovascular responsiveness and these brain aging markers. Hence, the findings are a prelude to further investigation into cerebrovascular responsiveness and its links to brain aging. Long-term development of markers of cerebrovascular responsiveness may provide researchers and clinicians with surrogate markers of brain pathological risk, i.e., a non-invasive marker of stroke or dementia risk. This could then serve as the basis for implementing brain-sparing interventions, particularly exercise interventions in high-risk populations. Therefore, this work lays the foundation for assessing whether longitudinal exercise-induced cerebrovascular functions could serve as potential indicators of brain aging

An investigation into the effects of commencing haemodialysis in the critically ill

<b>Introduction:</b> We have aimed to describe haemodynamic changes when haemodialysis is instituted in the critically ill. 3 hypotheses are tested: 1)The initial session is associated with cardiovascular instability, 2)The initial session is associated with more cardiovascular instability compared to subsequent sessions, and 3)Looking at unstable sessions alone, there will be a greater proportion of potentially harmful changes in the initial sessions compared to subsequent ones. <b>Methods:</b> Data was collected for 209 patients, identifying 1605 dialysis sessions. Analysis was performed on hourly records, classifying sessions as stable/unstable by a cutoff of >+/-20% change in baseline physiology (HR/MAP). Data from 3 hours prior, and 4 hours after dialysis was included, and average and minimum values derived. 3 time comparisons were made (pre-HD:during, during HD:post, pre-HD:post). Initial sessions were analysed separately from subsequent sessions to derive 2 groups. If a session was identified as being unstable, then the nature of instability was examined by recording whether changes crossed defined physiological ranges. The changes seen in unstable sessions could be described as to their effects: being harmful/potentially harmful, or beneficial/potentially beneficial. <b>Results:</b> Discarding incomplete data, 181 initial and 1382 subsequent sessions were analysed. A session was deemed to be stable if there was no significant change (>+/-20%) in the time-averaged or minimum MAP/HR across time comparisons. By this definition 85/181 initial sessions were unstable (47%, 95% CI SEM 39.8-54.2). Therefore Hypothesis 1 is accepted. This compares to 44% of subsequent sessions (95% CI 41.1-46.3). Comparing these proportions and their respective CI gives a 95% CI for the standard error of the difference of -4% to 10%. Therefore Hypothesis 2 is rejected. In initial sessions there were 92/1020 harmful changes. This gives a proportion of 9.0% (95% CI SEM 7.4-10.9). In the subsequent sessions there were 712/7248 harmful changes. This gives a proportion of 9.8% (95% CI SEM 9.1-10.5). Comparing the two unpaired proportions gives a difference of -0.08% with a 95% CI of the SE of the difference of -2.5 to +1.2. Hypothesis 3 is rejected. Fisher’s exact test gives a result of p=0.68, reinforcing the lack of significant variance. <b>Conclusions:</b> Our results reject the claims that using haemodialysis is an inherently unstable choice of therapy. Although proportionally more of the initial sessions are classed as unstable, the majority of MAP and HR changes are beneficial in nature