Assessing mechanical properties of the cardiovascular system

The elasticity of wall of the arteries plays a significant role in cardiovascular system. Capacitance of the aorta is predicative of cardiovascular events[1]. To get better understanding the function of the cardiovascular system, special attention should be paid to digest the traditional two-element Windkessel model. Because the Windkessel model provides information of cardiovascular function and which may be useful for prevention and diagnosis of hypertension. Our research presents a series of in vitro experimental studies of compliance, peripheral resistance, and pulse waves. In this thesis, several studies have been achieved: 1) a mathematical model for the capacitance of the aorta is derived based upon the conservation of mass, and a specialized test device provided by BDC Laboratories is used to simulate the aorta by employing an arched silicone-rubber tube with a known capacitance. 2) applied and compared arterial compliance determined from blood pressure, arterial compliance determined from PWV, and mechanical capacitance in flexible tubes and animal calf aortae. 3) investigated using sensitivity analysis as the analytical technique to determine parameters which. 4) develop a new technique which based on blood pressure diagram of flexible tubes and animal aortas. In the first study corresponding to chapter five, that the entire blood-pressure state may be plotted on a single blood-pressure diagram using three nondimensional groups. This diagram illustrates the impact of altering the capacitance and ejection period on the pulse pressure that exists within the aorta. In the second study corresponding to chapter six, the sensitivity analysis that has been used to figure out sensitivity coefficients with the largest magnitude is based on the most sensitive parameter that can be adjusted if we want to alter a pressure. In the third study corresponding to chapter seven, arterial compliance determined from blood pressure is more straightforward approach than arterial compliance determined from PWV to measuring the arterial stiffness. By that allowing hypertension to be managed. In the last study corresponding to chapter seven, it is figured out that total cardiovascular capacitance plays a significant role in determining the risk factors for cardiovascular disease, and the systolic and diastolic pressures during the cardiac cycle. In addition to cardiovascular capacitance other parameters that contribute to creating blood pressure include total peripheral resistance, stroke volume, ejection period, and heartrate. In conclusion, this research, combined with additional support may permit the realization for measuring arterial stiffness in the home setting. This research may make significant paradigm changes in prognosis and diagnosis of arterial stiffness and other cardiovascular events.Includes bibliographical references (pages 188-194)

To Study the Hemodynamic Changes from Supine to Prone Position in Asa II and III Patients Undergoing Major Spine Surgery in Prone Position using Flo Trac Sensor: An Observational Study

OBJECTIVES: This observational study assessed the hemodynamic changes that occurred in ASA II and III patients undergoing major elective spine surgery on changing position from supine to prone using the Flo Trac sensor. Additionally, it observed the effect of 10ml/kg of crystalloid fluid administered as a bolus before turning prone. METHODS: Twenty-nine patients were prospectively studied. Patients with valvular heart disease, chronic obstructive pulmonary disease, renal dysfunction and arrhythmia were excluded .After establishing venous access, radial arterial cannulation was undertaken and the Flotrac transducer was connected. Other routine monitors were connected. Induction was carried out with fentanyl, propofol and vecuronium; patients were intubated and mechanical ventilation established with tidal volumes of at least 8ml/kg. Anaesthesia was maintained with air /oxygen and Isoflurane titrated to a MAC of 0.8. Variables measured were heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), stroke volume variation (SVV), pulse pressure variation (PPV), cardiac output (CO) and cardiac index(CI).Variables were measured after induction in the supine position (T1) and every 5 minutes after turning prone up to 15 minutes (T2-T4). All patients received fluid bolus of 10ml/kg of crystalloids before change of position. A fall in cardiac index by more than 20% from baseline (T1) warranted treatment with crytalloids upto 10ml/kg and/or boluses of vasopressors. Failure to respond to these warranted starting inotropic agents. Statistical analysis was performed using SPSS software. A General Estimating Equations (GEE) analysis was performed to analyze the change in variables across the time points (T2-T4) along with the significance of change (p value), with T1 as the reference. A paired t-test analysis was additionally done between time points T1 and T4. Correlation between variables (PPV and CO, SVV and CO and PPV and SVV) were assessed in the prone position at two time points using Pearson correlation test. Levene's test for Equality of Variance was used to analyse the difference in variables among patients on differing prone supports and among diabetic versus non-diabetic patients. RESULTS: There was a significant change in SBP (p=0.025), SVV (p=0.002) and PPV(p=0.02) 5 minutes after change of position to prone. However, there was no significant fall (p>0.05) in CO or CI during this time. There was a significant change in all hemodynamic variables (HR: p<0.001, SBP p<0.001, MAP p=0.014, PPV:p=0.024, SVV p=0.002, CO p<0.001, CI: p=0.003) except DBP 15 minutes after turning prone. A strong positive correlation was found to exist between SVV and PPV at T2 (r=0.835; p=<0.001) and T4 (r=0.75; p<0.001) while CO correlated weakly with SVV and PPV. Type of support (Relton-Hall vs. bolsters) and presence of diabetes did not significantly affect PPV and SVV. In conclusion, there was a statistically significant change in all hemodynamic variables 15 minutes after turning prone. There was no significant fall in CO or CI 5 minutes after turning prone; whether this can be attributed to the fluid bolus administered before change in position cannot be established at present

Patient-specific design of the right ventricle to pulmonary artery conduit via computational analysis

Cardiovascular prostheses are routinely used in surgical procedures to address congenital malformations, for example establishing a pathway from the right ventricle to the pulmonary arteries (RV-PA) in pulmonary atresia and truncus arteriosus. Currently available options are fixed size and have limited durability. Hence, multiple re-operations are required to match the patients’ growth and address structural deterioration of the conduit. Moreover, the pre-set shape of these implants increases the complexity of operation to accommodate patient specific anatomy. The goal of the research group is to address these limitations by 3D printing geometrically customised implants with growth capacity. In this study, patient-specific geometrical models of the heart were constructed by segmenting MRI data of patients using Mimics inPrint 2.0. Computational Fluid Dynamics (CFD) analysis was performed, using ANSYS CFX, to design customised geometries with better haemodynamic performance. CFD simulations showed that customisation of a replacement RV-PA conduit can improve its performance. For instance, mechanical energy dissipation and wall shear stress can be significantly reduced. Finite Element modelling also allowed prediction of the suitable thickness of a synthetic material to replicate the behaviour of pulmonary artery wall under arterial pressures. Hence, eliminating costly and time-consuming experiments based on trial-and-error. In conclusion, it is shown that patient-specific design is feasible, and these designs are likely to improve the flow dynamics of the RV-PA connection. Modelling also provides information for optimisation of biomaterial. In time, 3D printing a customised implant may simplify replacement procedures and potentially reduce the number of operations required over a life time, bringing substantial improvements in quality of life to the patient

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

Performance Characteristics of Centrifugal Pump Impeller for Heart Failure Therapy: Numerical and In-vitro Approach

PhDHeart failure (HF) is a common cause of hospitalisation and mortality across industrialised countries. The number of hospitalisations and deaths attributed to heart failure is increasing, and this trend is predicted to continue. Numerical and in-vitro simulations of the human cardiovascular system constitute the basic tools for enhancing diagnostic and therapeutic technologies for HF and this would in turn, have significant effects on morbidity,mortality, and healthcare expenditure. Mechanical Circulatory Support (MCS) as a destination therapy for HF is rising significantly as it provides a cost-effective alternative to long-term treatment and cardiac transplantation. However, long-term versatility is far from ideal and incidence of transient and permanent neurological events is still high. To this end, evolution of MCS devices calls for more sophisticated design and evaluation methods. The purpose of this work is to develop a numerical model and to implemented a novel in-vitro model of the cardiovascular system with the intention of evaluating the performance characteristics of a purposely selected centrifugal pump impeller for the treatment of both Class III and IV HF conditions when placed in series with the heart at two different anatomic locations: Ascending Aorta and Descending Aorta. An existing lumped-parameter model of the CV system, that included models for the heart, the pulmonary and the systemic circulatory loops by adapting a modified version of the fourth-element Windkessel model was enhanced by dividing the systemic circulation into six parallel vascular beds, and by including an autoregulatory system to control both pressures and volumes throughout the system. As part of the novelty of the present work, a volume reflex loop was included with the purpose of simulating volume overload conditions, as commonly found in HF conditions, and obtaining a more realistic analysis of volume displacement, while using a MCS device. The in-vitro model implemented in this work adopted most of the features included in the mathematical counterpart with the purpose of validating the numerical results. As a result of the combination of models and proper optimisation of the system parameters, predictions of pathophysiological trends and MCS usage are satisfactorily obtained. The models implemented in this work offer a valuable tool for the selection and performance evaluation of MCS devices for the treatment of HF conditions

Clinically feasible model-based methods to guide cardiovascular fluid therapy in the ICU

Fluid therapy is one of the most commonly used clinical procedures employed in the ICU to treat circulatory shock. Approximately 30% of ICU patients receive a fluid therapy at some stage during their stay, with 20% of patients reviving it on the day of admission. By increasing the total volume in the circulation, clinicians aim to stimulate an increase in cardiac output, helping restore or maintain adequate organ and tissue perfusion. However, only ≈50% of patients receiving a fluid therapy will have also have the desired increase in cardiac output. Furthermore, excessive fluids have been strongly associated with worsened patient outcome and can negate the effects of earlier successful treatment. Therefore, knowledge of a patient’s fluid responsiveness, prior to administering of treatment is essential for safe treatment. Current, clinically used, indices of fluid responsiveness have a number of inherent limitations restricting their applicability or invalidating their use altogether. A recently developed model of the cardiovascular system showed a new index, model based stressed blood volume, to be a potential improvement over currently available indices, but required measurements from inside the cardiac chambers and central arteries for identification, which are not available in standard ICU care. This thesis develops a series of novel methods for estimating the required cardiovascular waveforms required for model identification from currently available clinical measurements. Thus, developing a clinically feasible model-based method to guide fluid therapy in the ICU. The first part of this work introduces the relevant physiology of the cardiovascular system is introduced along with the principles of the circulation driving flow to and from the heart. Next, a brief overview of current indices of fluid responsiveness is given, highlighting their advantages and limitations. Stressed blood volume, in the context of fluid responsiveness, is also introduced. The three-chamber lumped parameter model of the cardiovascular system is then introduced. Each component of the model and all model equations, including the equations governing model dynamics and equations for initial parameter estimation, are detailed. An initial study showing the implementation of the three chambered model is performed to highlight the clinical utility of identified parameters in assessing changes in patient condition. This study was performed on several porcine endotoxin experiments and provided the reference model parameters used to compare the final, clinically feasible method. A subsequent study is performed using the first method introduced to achieve clinical feasibility by removing the requirement of direct cardiac measurements by estimating left ventricle pressure and volume from aortic pressure. Because aortic pressure is also not available in standard ICU environments, the next section of work aimed to develop a method of estimating central pressure. A tube-load model of the arterial system was used to develop and test a novel method of estimating central pressure from commonly available peripheral pressure measurements, via an arterial transfer function, and nothing else. The transfer corresponding flow waveforms were then used, with an initial calibration measurement, to estimate stroke volume in the porcine endotoxin experiments. The final part of his thesis begins by consolidating all developed methods to identify the three-chambered model parameters from an anticipated clinically available subset of measurements from the porcine experiments. Finally, the model, and associated methods for estimating the required inputs, are used to assess fluid responsiveness in patient data obtained from the Christchurch hospital ICU in New Zealand. Overall, this thesis provides a method of identifying the parameters of model of the cardiovascular system model from a minimal, currently available, set of clinical measurements. Model-based stressed blood volume, identified using the three-chambered model, has the physiological basis, animal study validation, and now clinical feasibility, to be considered a potential diagnostic tool in the ICU. The intrinsic relation between stressed blood volume, perfusion pressure and fluid responsiveness means the methods proposed in this thesis may significantly improve a clinicians ability to safely and effective guide fluid therapy

Advanced bioimpedance signal processing techniques for hemodynamic monitoring during anesthesia

Aplicat embargament des de la data de defensa fins els maig 2020.Cardiac output (CO) defines the blood flow arriving from the heart to the different organs in the body and it is thus a primary determinant of global 02 transport. Cardiac output has traditionally been measured using invasive methods, whose risk sometimes exceeds the advantages of a cardiac output monitoring. In this context, the minimization of risk in new noninvasive technologies for CO monitoring could translate into major advantages for clinicians, hospitals and patients: ease of usage and availability, reduced recovery time, and improved patient outcome. Impedance Cardiography (ICG) is a promising noninvasive technology for cardiac output monitoring but available information on the ICG signals is more scare than other physiological signals such as the electrocardiogram (ECG). The present Doctoral Thesis contributes to the development of signal treatment techniques for the ICG in order to create an innovative hemodynamic monitor. First, an extensive literature review is provided regarding the basics of the clinical background in which cardiac output monitoring is used and concerning the state of the art of cardiac output monitors on the market. This Doctoral Thesis has produced a considerable amount of clinical data which is also explained in detail. These clinical data are also useful to complement the theoretical explanation of patient indices such as heart rate variability, blood flow and blood pressure. In addition, a new method to create synthetic biomedical signals with known time-frequency characteristics is introduced. One of the first analysis in this Doctoral Thesis studies the time difference between peak points of the heart beats in the ECG and the ICG: the RC segment. This RC segment is a measure of the time delay between electrical and mechanical activity of the heart. The relationship of the RC segment with blood pressure and heart interval is analyzed. The concordance of beat durations of both the electrocardiogram and the impedance cardiogram is one of the key results to develop new artefact detection algorithms and the RC could also have an impact in describing the hemodynamics of a patient. Time-frequency distributions (TFDs) are also used to characterize how the frequency content in impedance cardiography signals change with time. Since TFDs are calculated using concrete kernels, a new method to select the best kernel by using synthetic signals is presented. Optimized TFDs of ICG signals are then calculated to extract severa! features which are used to discriminate between different anesthesia states in patients undergoing surgery. TFD-derived features are also used to describe the whole surgical operations. Relationships between TFD-derived features are analyzed and prediction models for cardiac output are designed. These prediction models prove that the TFD-derived features are related to the patients' cardiac output. Finally, a validation study for the qCO monitor is presented. The qCO monitor has been designed using sorne of the techniques which are consequence of this Doctoral Thesis. The main outputs of this work have been protected with a patent which has already been filed. As a conclusion, this Doctoral Thesis has produced a considerable amount of clinical data and a variety of analysis and processing techniques of impedance cardiography signals which have been included into commercial medical devices already available on the market.El gasto cardíaco (GC) define el flujo de sangre que llega desde el corazón a los distintos órganos del cuerpo y es, por tanto, un determinante primario del transporte global de oxígeno. Se ha medido tradicionalmente usando métodos invasivos cuyos riesgos excedían en ocasiones las ventajas de su monitorización. En este contexto, la minimización del riesgo de la monitorización del gasto cardíaco en nuevas tecnologías no invasivas podría traducirse en mayores ventajas para médicos, hospitales y pacientes: facilidad de uso, disponibilidad del equipamiento y menor tiempo de recuperación y mejores resultados en el paciente. La impedancio-cardiografía o cardiografía de impedancia (ICG} es una prometedora tecnología no invasiva para la monitorización del gasto cardíaco. Sin embargo, la información disponible sobre las señales de ICG es más escasa que otras señales fisiológicas como el electrocardiograma (ECG). La presente Tesis Doctoral contribuye al desarrollo de técnicas de tratamiento de señal de ICG para así crear un monitor hemodinámico innovador. En primer lugar, se proporciona una extensa revisión bibliográfica sobre los aspectos básicos del contexto clínico en el que se utiliza la monitorización del gasto cardíaco así como sobre el estado del arte de los monitores de gasto cardíaco que existen en el mercado. Esta Tesis Doctoral ha producido una considerable cantidad de datos clínicos que también se explican en detalle. Dichos datos clínicos también son útiles para complementar las explicaciones teóricas de los índices de paciente de variabilidad cardíaca y el flujo y la presión sanguíneos. Además, se presenta un nuevo método de creación de señales sintéticas biomédicas con características de tiempo-frecuencia conocidas. Uno de los primeros análisis de esta Tesis Doctoral estudia la diferencia temporal entre los picos de los latidos cardíacos del ECG y del ICG: el segmento RC. Este segmento RC es una medida del retardo temporal entre la actividad eléctrica y mecánica del corazón. Se analiza la relación del segmento RC con la presión arterial y el intervalo cardíaco. La concordancia entre la duración de los latidos del ECG y del ICG es uno de los resultados claves para desarrollar nuevos algoritmos de detección de artefactos y el segmento RC también podría ser relevante en la descripción de la hemodinámica de los pacientes. Las distribuciones de tiempo-frecuencia (TFD, por sus siglas en inglés) se utilizan para caracterizar cómo el contenido de las señales de impedancia cardiográfica cambia con el tiempo. Dado que las TFDs deben calcularse usando núcleos (kernels, en inglés) concretos, se presenta un nuevo método para seleccionar el mejor núcleo mediante el uso de señales sintéticas. Las TFDs de ICG optimizadas se calculan para extraer distintas características que son usadas para discriminar entre los diferentes estados de anestesia en pacientes sometidos a procesos quirúrgicos. Las características derivadas de las distribuciones de tiempo-frecuencia también son utilizadas para describir las operaciones quirúrgicas durante toda su extensión temporal. La relación entre dichas características son analizadas y se proponen distintos modelos de predicción para el gasto cardíaco. Estos modelos de predicción demuestran que las características derivadas de las distribuciones tiempo-frecuencia de señales de ICG están relacionadas con el gasto cardíaco de los pacientes. Finalmente, se presenta un estudio de validación del monitor qCO, diseñado con alguna de las técnicas que son consecuencia de esta Tesis Doctoral. Las principales conclusiones de este trabajo han sido protegidas con una patente que ya ha sido registrada. Como conclusión, esta Tesis Doctoral ha producido una considerable cantidad de datos clínicos y una variedad de técnicas de procesado y análisis de señales de cardiografía de impedancia que han sido incluidas en dispositivos biomédicos disponibles en el mercadoPostprint (published version

Advanced bioimpedance signal processing techniques for hemodynamic monitoring during anesthesia

Cardiac output (CO) defines the blood flow arriving from the heart to the different organs in the body and it is thus a primary determinant of global 02 transport. Cardiac output has traditionally been measured using invasive methods, whose risk sometimes exceeds the advantages of a cardiac output monitoring. In this context, the minimization of risk in new noninvasive technologies for CO monitoring could translate into major advantages for clinicians, hospitals and patients: ease of usage and availability, reduced recovery time, and improved patient outcome. Impedance Cardiography (ICG) is a promising noninvasive technology for cardiac output monitoring but available information on the ICG signals is more scare than other physiological signals such as the electrocardiogram (ECG). The present Doctoral Thesis contributes to the development of signal treatment techniques for the ICG in order to create an innovative hemodynamic monitor. First, an extensive literature review is provided regarding the basics of the clinical background in which cardiac output monitoring is used and concerning the state of the art of cardiac output monitors on the market. This Doctoral Thesis has produced a considerable amount of clinical data which is also explained in detail. These clinical data are also useful to complement the theoretical explanation of patient indices such as heart rate variability, blood flow and blood pressure. In addition, a new method to create synthetic biomedical signals with known time-frequency characteristics is introduced. One of the first analysis in this Doctoral Thesis studies the time difference between peak points of the heart beats in the ECG and the ICG: the RC segment. This RC segment is a measure of the time delay between electrical and mechanical activity of the heart. The relationship of the RC segment with blood pressure and heart interval is analyzed. The concordance of beat durations of both the electrocardiogram and the impedance cardiogram is one of the key results to develop new artefact detection algorithms and the RC could also have an impact in describing the hemodynamics of a patient. Time-frequency distributions (TFDs) are also used to characterize how the frequency content in impedance cardiography signals change with time. Since TFDs are calculated using concrete kernels, a new method to select the best kernel by using synthetic signals is presented. Optimized TFDs of ICG signals are then calculated to extract severa! features which are used to discriminate between different anesthesia states in patients undergoing surgery. TFD-derived features are also used to describe the whole surgical operations. Relationships between TFD-derived features are analyzed and prediction models for cardiac output are designed. These prediction models prove that the TFD-derived features are related to the patients' cardiac output. Finally, a validation study for the qCO monitor is presented. The qCO monitor has been designed using sorne of the techniques which are consequence of this Doctoral Thesis. The main outputs of this work have been protected with a patent which has already been filed. As a conclusion, this Doctoral Thesis has produced a considerable amount of clinical data and a variety of analysis and processing techniques of impedance cardiography signals which have been included into commercial medical devices already available on the market.El gasto cardíaco (GC) define el flujo de sangre que llega desde el corazón a los distintos órganos del cuerpo y es, por tanto, un determinante primario del transporte global de oxígeno. Se ha medido tradicionalmente usando métodos invasivos cuyos riesgos excedían en ocasiones las ventajas de su monitorización. En este contexto, la minimización del riesgo de la monitorización del gasto cardíaco en nuevas tecnologías no invasivas podría traducirse en mayores ventajas para médicos, hospitales y pacientes: facilidad de uso, disponibilidad del equipamiento y menor tiempo de recuperación y mejores resultados en el paciente. La impedancio-cardiografía o cardiografía de impedancia (ICG} es una prometedora tecnología no invasiva para la monitorización del gasto cardíaco. Sin embargo, la información disponible sobre las señales de ICG es más escasa que otras señales fisiológicas como el electrocardiograma (ECG). La presente Tesis Doctoral contribuye al desarrollo de técnicas de tratamiento de señal de ICG para así crear un monitor hemodinámico innovador. En primer lugar, se proporciona una extensa revisión bibliográfica sobre los aspectos básicos del contexto clínico en el que se utiliza la monitorización del gasto cardíaco así como sobre el estado del arte de los monitores de gasto cardíaco que existen en el mercado. Esta Tesis Doctoral ha producido una considerable cantidad de datos clínicos que también se explican en detalle. Dichos datos clínicos también son útiles para complementar las explicaciones teóricas de los índices de paciente de variabilidad cardíaca y el flujo y la presión sanguíneos. Además, se presenta un nuevo método de creación de señales sintéticas biomédicas con características de tiempo-frecuencia conocidas. Uno de los primeros análisis de esta Tesis Doctoral estudia la diferencia temporal entre los picos de los latidos cardíacos del ECG y del ICG: el segmento RC. Este segmento RC es una medida del retardo temporal entre la actividad eléctrica y mecánica del corazón. Se analiza la relación del segmento RC con la presión arterial y el intervalo cardíaco. La concordancia entre la duración de los latidos del ECG y del ICG es uno de los resultados claves para desarrollar nuevos algoritmos de detección de artefactos y el segmento RC también podría ser relevante en la descripción de la hemodinámica de los pacientes. Las distribuciones de tiempo-frecuencia (TFD, por sus siglas en inglés) se utilizan para caracterizar cómo el contenido de las señales de impedancia cardiográfica cambia con el tiempo. Dado que las TFDs deben calcularse usando núcleos (kernels, en inglés) concretos, se presenta un nuevo método para seleccionar el mejor núcleo mediante el uso de señales sintéticas. Las TFDs de ICG optimizadas se calculan para extraer distintas características que son usadas para discriminar entre los diferentes estados de anestesia en pacientes sometidos a procesos quirúrgicos. Las características derivadas de las distribuciones de tiempo-frecuencia también son utilizadas para describir las operaciones quirúrgicas durante toda su extensión temporal. La relación entre dichas características son analizadas y se proponen distintos modelos de predicción para el gasto cardíaco. Estos modelos de predicción demuestran que las características derivadas de las distribuciones tiempo-frecuencia de señales de ICG están relacionadas con el gasto cardíaco de los pacientes. Finalmente, se presenta un estudio de validación del monitor qCO, diseñado con alguna de las técnicas que son consecuencia de esta Tesis Doctoral. Las principales conclusiones de este trabajo han sido protegidas con una patente que ya ha sido registrada. Como conclusión, esta Tesis Doctoral ha producido una considerable cantidad de datos clínicos y una variedad de técnicas de procesado y análisis de señales de cardiografía de impedancia que han sido incluidas en dispositivos biomédicos disponibles en el mercad