No description available.

Fluid drainage via the lymphatics prevents swelling due to excess fluid in interstitial space. Since interstitial fluid volume can vary dramatically, the function of lymphangions are rather dynamic so that they can contend with the wide ranges of lymph flow and pressure. Sharing with blood vessels an acute sensitivity to mechanical stresses, lymphangions could be expected to be similarly sensitive to prolonged changes in transmural pressure and flow. The purpose of this research was to quantify the adaptation of lymphangions to prolonged alterations in lymph hydrodynamics and to investigate how adaptation of individual lymphangions acts together within a network to affect the regulation of lymph flow. In project I, bovine postnodal mesenteric lymphatic vessels were partially occluded for three days, which divided the vessel into two segments. Both segments, therefore, were exposed to the same flow but different transmural pressures. In project II, an isometric preparation was employed to study developed wall tension in lymphangions exposed to mesenteric venous hypertension. In project III, an analytical model of a symmetrical lymphatic network was developed to investigate how its pressure-flow relationship emerges from the complex interaction of its pumping lymphangions. Results from this research indicate that lymphangions become stronger pumps when exposed to prolonged increases in transmural pressure, but exposure to prolonged venous hypertension attenuates lymphangion pumping. The main mechanism for lymphangion adaptation is the alteration of preload-dependent maximal tension developed by lymphatic muscle. Lower cytosolic Ca2+ concentration is likely to be the underlying cause for weaker developed tension. The analytical model suggests that the ratio of lymphangion systolic contractility to diastolic stiffness results in a differential response of lymph flow to changes in inlet and outlet pressures. This differential sensitivity to inlet and outlet pressures allows homeostatic responses to both microvascular and venous hypertension, and provides a framework for interpreting the functional implications of chronic lymphangion adaption.

<p>The cardiac wall has complex three-dimensional fiber structures and mechanical properties that enable the heart to efficiently pump the blood through the body. By studying the myocardial strains induced during diastole, information about the pumping performance of the heart and what mechanisms that are responsible for this effective blood filling, can be achieved. Two different computation methods for myocardial strain, both based on data acquired from marker technique, were compared using a theoretical cylinder model. The non-homogeneous polynomial fitting method yielded higher accuracy than a homogeneous tetrahedron method, and was further used to investigate cardiac and fiber strains at different wall depths and myocardial regions in normal and ischemic ovine hearts. Large spatial and regional variations were found, as well as alterations, conveyed by ischemic conditions, of fiber mechanisms responsible for the circumferential expansion and wall thinning during diastole.</p>

The cardiac wall has complex three-dimensional fiber structures and mechanical properties that enable the heart to efficiently pump the blood through the body. By studying the myocardial strains induced during diastole, information about the pumping performance of the heart and what mechanisms that are responsible for this effective blood filling, can be achieved. Two different computation methods for myocardial strain, both based on data acquired from marker technique, were compared using a theoretical cylinder model. The non-homogeneous polynomial fitting method yielded higher accuracy than a homogeneous tetrahedron method, and was further used to investigate cardiac and fiber strains at different wall depths and myocardial regions in normal and ischemic ovine hearts. Large spatial and regional variations were found, as well as alterations, conveyed by ischemic conditions, of fiber mechanisms responsible for the circumferential expansion and wall thinning during diastole.

No description available.

The left ventricle of the heart relaxes when it fills with blood and contracts to eject blood into circulation to meet the body’s metabolic demands. Dysfunction in either relaxation or contraction of the left ventricle can lead to heart failure. Transmural heterogeneity is thought to contribute to normal ventricular wall motion but it is not well understood how transmural modifications affect the failing left ventricle. The overall hypothesis of this dissertation is that normal left ventricles exhibit transmural heterogeneity in cellular level contractile properties and with aging and heart failure there are region-specific changes in cellular level contractile mechanisms. Age is the biggest risk factor associated with heart failure and therefore we investigated transmural changes in Ca2+ handling and contractile proteins in aging F344 rats before the onset of heart failure. We found that in 22-month old F344 rats there is a region-specific decrease in cardiac troponin I phosphorylation in the sub-epicardium that may contribute to slowed myocyte relaxation in the sub-epicardial cells of the same age. We then investigated the transmural patterns of contractile properties in myocardial tissue samples from patients with heart failure. Force and power output reduced most significantly in the samples from the mid-myocardial region when compared to sub-epicardium and sub-endocardium of the failing hearts. There was a region-specific increase in fibrosis is the mid-myocardium of the failing hearts. Myocardial power output was correlated with key sarcomeric proteins including cardiac troponin I, desmin and myosin light chain-1. The results in this dissertation reveal novel region-specific modifications in contractile properties in aging and heart failure. These transmural effects can potentially contribute to disruption in normal wall motion and lead to ventricular dysfunction.

Catheter ablation is a unique method for cardiac arrhythmias treatment based on creating spot lesions of radiofrequency energy using intracardiac ablation catheter. Transmurality of these lesions should be achieved for long-term therapeutic treatment effect. The degree of myocardial damage depth is reflected in the parameters of sensed intracardiac ECG. From research studies is evident that the change in morphology and deflection of ablation signal play a key role in the assessment of transmurality. This thesis consists of theoretical introduction to electrophysiology, proposal and realization of methods for objective assessment of transmurality by processing signals in time, frequency and time – frequency domain. The end of this diploma thesis includes the statistical analysis of these clinical dat and comparison of methods.

Hay una concienciación cada vez mayor de la importancia de diferencias entre los hombres y las mujeres, en edad adulta y preadolescencia, en la fisiología y la patofisiología del sistema cardiovascular. Una de las diferencias más importantes entre los hombres y las mujeres con respecto a sexo y a arritmias es el mayor riesgo en mujeres de una taquicardia ventricular polimórfica, conocida como Torsade de Pointes (TdP), inducida por las drogas que prolongan la repolarización. Además, el género femenino es un factor de riesgo independiente para el síncope y la muerte súbita en el síndrome de QT largo congénito (SQTL), mientras los preadolescentes varones presentan un mayor número de eventos cardiacos cuya letalidad es más alta que en preadolescentes del sexo femenino. En este trabajo se han formulado nuevos modelos computacionales que permiten simular las diferencias relacionadas al sexo y la edad en mamíferos. Los modelos de adulto macho, adulto hembra, preadolescente macho y preadolescente hembra incluyen las características electrofisiológicas de tejidos epicardial, midmiocardial y endocardial haciendo posible la simulación de la heterogeneidad transmural del ventrículo. Se modelizaron los efectos del fármaco antiarrítmico dofetilide con las formulaciones de Hodgkin Huxley y Markov y se simularon la acción de este fármaco en los modelos de adulto macho, adulto hembra, preadolescente macho y preadolescente hembra, tanto en células de cardiomiocitos como células del canal hERG, incluidas tipo wild type y de mutaciones en condiciones normales como en condiciones patológicas. En esta investigación se observó como el dofetilide redujo la componente rápida de la corriente de rectificación tardía produciendo una mayor prolongación en la duración del potencial de acción (APD), incrementando la incidencia de postdepolarizaciones tempranas (EADs) y aumentando la dispersión transmural de repolarización (DOR) en todos los modelos. En base a los resultados en las diferencias r / González Garza, RS. (2011). Diferencias relacionadas al sexo y la edad bajo los efectos de mutaciones y el fármaco Dofetilide [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/11404