544 research outputs found

    Microvascular Responsiveness to Cardiopulmonary Bypass

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    Cardiopulmonary bypass can result in multiple organ failure due to mechanisms of ischemia reperfusion injury and the systemic inflammatory response syndrome. The primary objective of this thesis was to investigate and monitor the microvasculature in cardiac surgery patients using multiple methodologies and real-time monitoring techniques. The purpose of our first study was to determine whether pulsatile blood flow during bypass improves microvascular perfusion compared to non-pulsatile flow. We found that changes in sublingual mucosal microcirculation using orthogonal polarization spectral imaging correlate with indices of thenar muscle tissue oxygen saturation and its recovery during a vascular occlusion test using near-infrared spectroscopy in both groups. There were significantly fewer normally perfused vessels, along with impaired microvascular responsiveness and elevated levels of lactate in the non-pulsatile group. Although these technologies help to better understand the pathophysiology of acute circulatory failure, a need exists for improved monitors that can continuously track real-time changes in the microcirculation. Our subsequent studies involved the application of a custom broadband continuous wave near-infrared monitor to determine the feasibility of tracking microvascular hemoglobin content as a surrogate for red blood cell (RBC) flow in skeletal muscle during non-pulsatile bypass. We measure changes in optical density at the isosbestic wavelength as an index of change in hemoglobin over time. The changes in optical density relative to baseline values were continuously monitored throughout the procedure, and showed a positive correlation with various interventions during bypass and with potentially negative outcomes. In our third study we applied continuous wavelet transform analysis to the near-infrared data to reflect the dynamic variability in RBC distribution within the microvasculature as an indicator of autoregulation. We showed signal power composition varied within and between patients at all time points, and shifting of power distribution from high to low frequency ranges, and vice versa, in relation to specific events during the procedure. These studies support the potential for clinical devices that can be easily interpreted by a clinician in real-time to guide therapeutic targets and improve clinical outcomes. Our current research and related future work is an important first step and compelling pre-requisite for such a monitor

    Renal Perfusion in Human Septic Shock

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    Effects of general anaesthesia and intravenous fluid therapy on renal biomarkers in cats undergoing ovariohysterectomy : a thesis presented in partial fulfilment of the requirements for the degree of Master of Veterinary Science at Massey University, Manawatu, New Zealand

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    Figure 3 is re-used with permission.Traditional screening tests used to evaluate renal function have been demonstrated to be insensitive in detecting early kidney damage, such as subclinical acute kidney injury. It is probable that general anaesthesia and routinely performed surgical procedures could cause subclinical changes in the renal structure, predisposing the animal to subsequent functional impairment. However, these active changes might go undetected while screening using traditional renal markers, such as serum creatinine (SCr) and blood urea nitrogen (BUN). Novel urinary biomarkers, that indicate renal injury earlier than conventional markers, have been extensively studied in humans during the perioperative period. A feline model of mild acute kidney injury, potentially induced through general anaesthesia during routine surgeries, may prove useful in testing novel renal biomarkers and providing insight into the effects of anaesthesia on kidneys. A randomised controlled trial was performed using 60 healthy cats presented to the Massey University Veterinary Teaching Hospital for routine ovariohysterectomy. Blood and urine samples were collected immediately before (0 h), and after (24 and 48 h) anaesthesia and spay surgery. Traditional renal marker levels (SCr, BUN) were measured from the serum samples. Commercial assays were used to detect the levels of novel markers, such as N-acetyl-β-D glucosaminidase (NAG) enzyme, Neutrophil Gelatinase-associated Lipocalin (NGAL), Retinol Binding Protein (RBP) and Kidney Injury Molecule-1 (KIM-1), in the urine samples. This study aimed to use these urinary markers to investigate the effects of general anaesthesia and intraoperative fluid therapy on feline renal structure. Statistical tests such as t-test and ANOVA were conducted to establish differences in renal marker values between the time points and between treatment groups. Upon comparing the changes in renal marker concentrations, the study found no measurable evidence of structural or functional kidney damage in the cats. This is plausible since the vital parameters, such as arterial blood pressure and oxygenation levels, of the study cats were maintained within or near the borderline physiological range throughout the surgical procedure, resulting in the apparent absence of assessable kidney damage postoperatively. It is inferred that a more severe form of renal injury would be required to test the sensitivity of these novel renal markers in cats

    Advances in Ophthalmology

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    This book focuses on the different aspects of ophthalmology - the medical science of diagnosis and treatment of eye disorders. Ophthalmology is divided into various clinical subspecialties, such as cornea, cataract, glaucoma, uveitis, retina, neuro-ophthalmology, pediatric ophthalmology, oncology, pathology, and oculoplastics. This book incorporates new developments as well as future perspectives in ophthalmology and is a balanced product between covering a wide range of diseases and expedited publication. It is intended to be the appetizer for other books to follow. Ophthalmologists, researchers, specialists, trainees, and general practitioners with an interest in ophthalmology will find this book interesting and useful

    Experimental, theoretical, and translational studies of RBC distribution in capillary networks

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    The purpose of this thesis was to evaluate the physiology of red blood cell (RBC) distribution in skeletal muscle capillary networks. Because this is the terminal site of oxygen exchange in the microcirculation, characterization of this fundamental process informs an understanding of how microvascular blood flow regulation matches oxygen supply with local tissue demand. Prior studies in this field have focused on small groups of capillaries, and have not linked capillary network structure with functional measurements, nor evaluated the temporal complexity of RBC distribution over physiologically-relevant scales. It is also unclear how the functional units called capillary modules – comprised of parallel capillaries from arteriole to venule – relate together within large capillary networks. In this thesis, we employed multiple methodologies to achieve this goal with preclinical animal models, theoretical simulations, and translational studies in human patients. First, we used intravital videomicroscopy of resting extensor digitorum longus muscle in rats and discovered that skeletal muscle capillary networks are organized into columns of interconnected capillary modules spanning thousands of microns – a structure we called the Capillary Fascicle. We showed that capillary-RBC hemodynamics are heterogeneous within a module and between modules. Next, we evaluated capillary module hemodynamics and demonstrated that RBC flow is independent of module resistance, providing evidence for regulation of driving pressure at the level of the capillary module, that requires pre- and post-capillary mechanisms of control. Using a dual-phase mathematical model of blood flow within artificial capillary module geometries, we showed that RBC flow heterogeneity is an intrinsic property of capillary module structure, and that variations to inflow hematocrit and pressure impact RBC distribution as a consequence of the rheological properties of microvascular blood flow. Finally, we used high-resolution near-infrared spectroscopy to monitor the temporal variability of hemoglobin content in skeletal muscle of patients in the intensive care unit (ICU). We showed that RBC perfusion characteristics are not consistent between patients, and that ICU interventions directly impact microvascular RBC distribution. Together, these studies support a theory of capillary networks as active participants in microvascular blood flow regulation, with structural features of capillary networks contributing to functional characteristics of RBC distribution

    Inotroopsete ravimite farmakokineetika ja farmakodünaamika vastsündinutel

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    Väitekirja elektrooniline versioon ei sisalda publikatsiooneSuurt osa vastsündinutel kasutatavatest ravimitest ei ole sellel populatsioonil põhjalikult uuritud. Sageli on ravimi doseerimise ja oodatava efekti osas võetud aluseks täiskasvanutel või suurematel lastel läbi viidud uuringute tulemused. Esimestel elutundidel, -päevadel ja -nädalatel aset leidvad füsioloogilised muutused mõjutavad ravimite jaotumist, toimet ja eliminatsiooni viisil, mida ei ole võimalik ennustada täiskasvanute või laste uuringutes kogutud andmete pealt. Käesoleva uurimistöös kogusime ja analüüsisime kahe vastsündinutel sageli kasutatava südant ja vereringet mõjutava ravimi – dobutamiini ja milrinooni – doseerimise, plasmakontsentratsiooni ja toimete vahelisi seoseid. Analüüsiks kasutasime mittelineaarseid segamõjudega mudeleid, mis lisaks kehas ravimiga (farmakokineetika) ja ravimi toimel toimuvatele (farmakodünaamika) protsessidele kirjeldavad ka indiviidide vahelisi variatsioone nendes protsessides ning juhusliku vea suurust, mis tekib ravimi manustamisel ja mõõtmiste teostamisel. Leidsime, et vereringe sünnijärgse ümberkohanemise ajal ilmneb dobutamiini toime südamesagedusele ja vererõhule juba suhteliselt madalatel kontsentratsioonidel ning on küllastuv, südame minutimahtu tõstev toime on uuritud doosi- ja kontsentratsioonivahemikus aga lineaarne või küllastub kõrgematel kontsentratsioonidel. Milrinooni farmakokineetika andmete alusel soovitame ravimi doseerimisskeemi, mis tagab avatud arterioosjuha ligeerimise järgselt ravi vajavatel vastsündinutel kõige suurema tõenäosusega ravimi kontsentratsiooni toimivas vahemikus. Käesolev töö lisab olulist uut teadmist ravimite kasutamiseks vastsündinutel kahes kriitilises olukorras, kus oodatava toime saavutamine, vältides samal ajal kõrvaltoimeid, on eluliselt tähtis.A lot of medications used in neonates are insufficiently studied in this vulnerable population. Often the dosing schemes and expected effects are extrapolated from adult or paediatric studies. Physiological changes within hours, days and weeks after birth affect the distribution, elimination and effect of medications in ways not predictable from adult and paediatric data. The present research analysed dosing, concentration and effect relationships of two cardiovascular medications – dobutamine and milrinone – in neonates in clinical situations where they are frequently used. Nonlinear mixed-effects modelling was used to describe the pharmacokinetic and pharmacodynamic processes with evaluation of interindividual variability and residual variability occurring during treatment and data collection. The effects of dobutamine on heart rate and blood pressure occur with relatively low concentrations and are saturable, contrarily the effect on cardiac output is linear throughout the studied dose- and concentration range or is saturable at higher concentrations. Based on the pharmacokinetic data, milrinone dosing regimen was suggested for preterm neonates undergoing patent arterial duct closure operation and at risk of postoperative respiratory and cardiac function deterioration. Additional to developmental changes the pharmacokinetics and pharmacodynamics of medications in neonates may be affected by the critical illness and intensive care, thereby the most valuable pharmacological data comes from the studies conducted in the particular situations where the effects are expected.https://www.ester.ee/record=b534663

    Machine Learning Algorithms for Classification of Microcirculation Images from Septic and Non-Septic Patients

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    Sepsis is a life-threatening disease and one of the major causes of death in hospitals. Imaging of microcirculatory dysfunction is a promising approach for automated diagnosis of sepsis. We report a machine learning classifier capable of distinguishing non-septic and septic images from dark field microcirculation videos of patients. The classifier achieves an accuracy of 89.45%. The area under the receiver operating characteristics of the classifier was 0.92, the precision was 0.92 and the recall was 0.84. Codes representing the learned feature space of trained classifier were visualized using t-SNE embedding and were separable and distinguished between images from critically ill and non-septic patients. Using an unsupervised convolutional autoencoder, independent of the clinical diagnosis, we also report clustering of learned features from a compressed representation associated with healthy images and those with microcirculatory dysfunction. The feature space used by our trained classifier to distinguish between images from septic and non-septic patients has potential diagnostic application.Comment: Accepted for publication at 2018 IEEE International Conference on Machine Learning and Applications (IEEE ICMLA
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