Large-scale modeling allows for a broad mechanistic view of a cardiopulmonary disease, often beyond what can be observed clinically. Our group has developed a large-scale model of the human cardiovascular-respiratory system (H-CRS) that integrates heart mechanics, hemodynamics, circulatory and gas transport aspects of the lung, brain and whole body tissue, and nervous system control of the cardiovascular and respiratory systems into a single model that can be used to analyze the dynamic behavior of the normal and deranged cardiopulmonary system. The model is a composite model based on data from multiple sources, developed over the years, and has been able to mimic responses to cardiovascular, respiratory, and nervous system activity, and accurately predict changes to environmental or diseased conditions. The ability of a large-scale model to portray many aspects of the cardiopulmonary system simultaneously is beyond the scope of clinical procedures, as providing such data becomes overly invasive, expensive, and risky. However, clinical questions can be pursued in virtual mode using modeling as a tool, and the hope is that modeling might also point to novel avenues to explore in disease diagnosis. In this work, we have advanced new conceptual framework of pericardial constraint, respiratory modulation, and septal pumping in the H-CRS model to address three important clinical topics. The first is cardiac tamponade (CT) which results from fluid accumulation in the pericardial sac; the second is left ventricular diastolic dysfunction (LVDD) which leads to congestive heart failure; the third is a hemodynamic analysis of the use of left ventricular rotary assist devices in systolic heart failure due to left ventricular systolic dysfunction (LVSD). These topics are highly relevant in the clinical setting, employ advanced methods for clinical diagnosis (with sufficient clinical data available for model validation), yet contain unanswered physiological questions for our modeling to explore. For example, the proposed modeling studies show that detailed mechanistic characterization of the diseases CT, LVDD, and LVSD exhibit model-generated results of known disease signs, but also reveal the significance of unexplored right heart symptoms and the important role of septal mechanics in these disease states. Left ventricular assist device (LVAD) modeling demonstrates improvement in cardiac output and reduced left heart work, but at the expense of septal functionality and right heart work. Our work in demonstrating the ability of a large-scale model to portray many complex aspects of the cardiopulmonary system simultaneously suggests that modeling might provide novel avenues to explore disease diagnosis, physiology, and management.

The diseases of cardiovascular system and the respiratory system have been the second and third killers causing deaths in Hong Kong. In this stressful civilized world, the prevalence and incidence of these diseases increased prominently which arouse our concern on the theories behind the pathological conditions. This report will focus on the biofluid mechanics in the large artery and in the upper airway. Thoracic aortic dissection, characterized by the tearing in the middle layer of vessel wall, is a catastrophic vascular disorder. The wall of the newly formed channel, the false lumen, is weakened and prone to aortic events. Endovascular repair is a minimally invasive technique for treating dissection patients. The biomechanical factors and the length of endograft were studied by computational fluid dynamics. Two geometrical factors showed a significant impact on the backflow in the false lumen. A larger false lumen and a larger distal tear size greatly affected the extent of thrombosis in the false lumen. It made the false lumen under a higher risk of vessel rupture. The computational prediction also demonstrated a more stable hemodynamic condition in the model with a longer endograft. These results provide important information for the clinicians to propose the surgical procedures and to improve the design of endografts. Airway obstruction is a common breathing disorder but it is always underdiagnosed. Obstructive sleep apnea (OSA) and different dentofacial deformities are two pathological conditions in which the patients have the abnormal sizes of airways. Computational fluid dynamic was employed in both conditions with patient–specific models. In the part of OSA, pre– and post–operative models were studied. The dimensions and flow resistance of the upper airway showed a significant improvement after mandibular distraction. The percentage of stenosis and the flow resistance was reduced by 27.3% and 40.7% respectively. For the patients in three facial skeletal deformity groups, the cross–sectional area and the flow resistance were compared. The patients with Class II deformity had the smallest retroglossal and retroplatal dimensions as well as the greatest flow resistance. The results confirmed the effectiveness of mandibular distraction and also provide valuable implications for the clinicians on the treatment planning, particularly for the Class II subjects. / published_or_final_version / Mechanical Engineering / Master / Master of Philosophy

The work described in this thesis has been carried out over the period 1958-1965, having been begun during the tenure of a residency at the University of Colorado, Denver, U.S.A. At this time, surgery for the closure of septal defects was being actively carried out, and interest was aroused, in two clinical features which were apparent from close contact with this programme. The first was the nature of the chest deformities associated with septal defects; the second, the striking alleviation of symptoms which followed successful closure of these defects. The reasons for these phenomena were by no means clear and the subsequent work has been concerned with an attempt to understand them.

Ectotherms regulate body temperature (Tb) primarily through behavioral interactions with their environment. These animals also have limited aerobic scopes and must rely on anaerobic metabolism to support intense activity; lactate byproduct and glycogen depletion are two consequences of anaerobic metabolism that must be dealt with during exercise recovery. It has been suggested that, in many ectothermic species, Tb may affect the rate of lactate clearance and glycogen repletion during recovery from intense exercise. This study investigated thermoregulatory behavior in Western Fence Lizards (Sceloporus occidentalis) to determine preferred Tb during exercise recovery. I hypothesized that animals would select higher Tb’sduring the recovery period on the basis that biochemical processes occur at faster rates at high temperatures, which may facilitate a more rapid reduction of lactate and replenishment of glycogen stores. However, it was found that control animals maintained a constant Tb of 33°C, while exercised animals cooled Tb to 30°C 20 minutes after exercising, and eventually warmed to 32°C by the 2 hour mark. Animals were found to be able to cool Tb by a maximum of 0.175°C/min given the available temperatures, which negated possible effects of temperature variation on Tb during exercise trials and transport. My results suggest a benefit of lowered Tb to facilitate exercise recovery in these animals. Behavioral hypothermia in S. occidentalis may be caused by physiological triggers associated with intense activity such as hypoxia, hypercapnia, or elevated blood lactate concentration. However, these speculations must be confirmed by further research.

Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xii, 278 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--West Virginia University, 2007. / Title from document title page. Document formatted into pages; contains xiv, 155 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

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