Between Dec 19, 2024 and Jan 2, 2025, datasets can be submitted to DRUM but will not be processed until after the break. Staff will not be available to answer email during this period, and will not be able to provide DOIs until after Jan 2. If you are in need of a DOI during this period, consider Dryad or OpenICPSR. Submission responses to the UDC may also be delayed during this time.

Browsing by Subject "Heart failure"

Now showing 1 - 15 of 15
  • Thumbnail Image
    Item
    Cardiac repair using fibrin patch-based enhanced delivery of stem cells and novel strategies for fast examination of myocaridal energetics in vivo using 31P magnetic resonance spectroscopy.
    (2011-03) Xiong, Qiang
    The dissertation is related to heart disease in both basic scientific and pre-clinic respects. Cardiovascular disease is a leading cause of death in the developed countries even with optimal medical treatment. Recently, the emerging stem cell biology has shown great potentials for cardiac repair. Using both large (swine) and small (rodent) animal models with ischemic heart disease, we examined the functional improvement of enhanced delivery of combined human embryonic stem cell-derived endothelial cells and smooth muscle cells via a fibrin 3D porous scaffold biomatrix. The integration of stem cell biology and tissue engineering has resulted in significant improvement of both regional and global left ventricle function as compared to untreated animals, demonstrating a promising therapeutic strategy of using this cell type and the novel mode of delivery. As a most energy demanding organ, the heart energetic status is tightly associated with the organ's physiological and pathological conditions. Based on the ultra-high-field magnetic resonance imaging/spectroscopy techniques, we developed a noninvasive modality for rapid examination of cardiac energetics in vivo. The new platform will offer unprecedented understanding into the relationship between the cardiac energetic status and the organ's physiological/pathological conditions, and thus it is of great potential in both basic scientific research and clinical diagnosis.
  • Thumbnail Image
    Item
    Cardiac Resynchronization Therapy Device-Programmed and Device-Measured Parameters as Predictors of Outcomes in Patients with Heart Failure
    (2017-10) Brown, Jason
    Heart failure (HF) is a major public health burden, with over 6.5 million adults in the US suffering from the disease. Moderate to advanced-stage heart failure patients implanted with cardiac resynchronization therapy (CRT) devices suffer from increased mortality risk and frequent inpatient hospitalization. Efforts to reduce mortality and prevent HF-related hospitalizations in this population would be of significant benefit to the patients, as well as to the health care system. In this doctoral dissertation, we present three manuscripts examining associations between CRT device-measured and device-programmed parameters and patient mortality and HF-hospitalization. In the first manuscript, we examined the device-measured parameter of intrathoracic impedance, and whether an OptiVol® threshold crossing or time above OptiVol® threshold were associated with patient mortality and HF-related hospitalization. We found that patients with >15.1% of their follow-time above threshold had a 4.2 times greater risk of mortality and a 3.2 times greater risk of HF-hospitalization than those patients with <4.1% of follow-up time above threshold. In addition, a single OptiVol® crossing was associated with an 87% higher mortality rate, and a 70% higher HF-hospitalization rate. In the second manuscript, we examined the device-measured associations between biventricular pacing percentage, AF burden, and heart rate variability on patient mortality and HF-related hospitalization. We found a complex relationship between biventricular pacing percentage, AF, AVN ablation, and HRV where patients with <99% bi-V pacing percentage had an increased rate of mortality and hospitalization among those with no baseline device-measured atrial fibrillation. In addition, AVN ablation was associated with worse outcomes among those with high baseline HRV, suggesting that the potential loss of benefits of higher HRV must be weighed when performing an AVN ablation procedure. The third manuscript looked at parameters associated with an increased risk of 30-day HF-related rehospitalization. We found that parameters associated with kidney function to be of critical importance in evaluating the risk of patients at higher risk of rehospitalization within 30 days. Patients with a daily intrathoracic impedance measurement >8less than the reference impedance value on the day of discharge, a diagnosis of chronic kidney disease, no diuretic prescription, male sex, longer duration of heart failure at the time of index hospitalization, and those with a prior CABG procedure to have a higher risk of 30-day rehospitalization. Model AUC, NRI, IDI, and Hosmer-Lemeshow statistics indicated good model discrimination with respect to a previously published model with good calibration
  • Thumbnail Image
    Item
    Echocardiographic Evaluation of Left Ventricular Recovery After Refractory Out-of-Hospital Cardiac Arrest
    (2020-12) Kalra, Rajat
    Background: The mechanisms and degree of myocardial recovery during treatment with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are unclear. We performed a descriptive study to evaluate myocardial recovery and changes in parameters of myocardial loading using echocardiography. Methods: We used a retrospective cohort design to evaluate patients with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest who were treated with the Minnesota Resuscitation Consortium protocol. Left ventricular ejection fraction (LVEF), end-diastolic diameter (LVEDD), end-systolic diameter (LVESD), and fractional shortening were assessed using serial echocardiography. One-way analysis of variance (ANOVA) was used to compare parameters over six hospitalization stages. Two-way ANOVA was used to compare these parameters between patients that died during the index hospitalization and patients that survived. Results: 77 patients had >1 echocardiographic turndown evaluations. Thirty-eight patients survived to discharge and 39 patients died. Of 39 in-hospital deaths, 17 patients died before VA-ECMO decannulation and 22 patients died after VA-ECMO decannulation. Among all patients, LVEF improved from 9.7±10.1% from the first echocardiogram after rewarming to 43.1±13.1% after decannulation (p<0.001) and fractional shortening ratio improved from 0.14±0.12 to 0.31±0.14 (p<0.001). The LVEDD and LVESD remained stable (p=0.36 and p=0.12, respectively). Patients that died had a lower LVEF by an average of 6.93% (95% confidence interval: -10.0 to -3.83, p<0.001), but other parameters were similar. Conclusion: Refractory cardiac arrest patients treated with VA-ECMO experience significant recovery of ventricular function during treatment. We postulate that this primarily occurs via reduction of LV preload.
  • Thumbnail Image
    Item
    Exercise Therapy and Heart Failure
    (2012-09-24) Dirksen, Lana
  • Thumbnail Image
    Item
    Heart failure and associated structural and functional remodeling: assessment employing various magnetic resonance imaging methodologies.
    (2009-11) Eggen, Michael D.
    Cardiovascular magnetic resonance imaging (MRI), or cardiac MR, is currently considered the "gold" standard for noninvasively characterizing cardiac function and viability, having 3D capabilities and a high spatial and temporal resolution. More recently, the capabilities of MRI have been extended to study tissue microstrucure and fiber orientation in both the brain and the heart through specially designed pulse sequences which are sensitive to diffusion. In this specialized imaging method, known as diffusion tensor magnetic resonance imaging (DTMRI), myofiber orientation can be probed in high resolution and this technique has been successfully utilized to study the helical arrangement of muscle fibers within the myocardium. As such, the counter-wound helical structure of the myocardium is considered to be responsible for the torsional or wringing motion of the left ventricle and serves three main mechanical functions: (1) equalizing myofiber strain and workload; (2) optimizing the volume of blood ejected during systole (stroke volume); and/or (3) storing torsional energy in the intracellular and extracellular matrices and, when released, increasing ventricular filling during diastole. Therefore, cardiac fiber orientation can also be considered as a primary determinant of ventricular pump function, and is of great clinical interest in the study of structure and function within either the normal or diseased heart. To date, the primary focus of cardiac DTMRI has been to characterize myofiber orientation in healthy animal hearts, with little progress in the study of myofiber arrangement in the diseased heart. As such, due to the long scan times required for in vivo DTMRI, and the limited availability of freshly excised human hearts for ex vivo imaging, data are limited in the characterization of fiber orientation in both healthy and diseased human hearts. Therefore, in my thesis research, the primary objective was to investigate myofiber orientation in both healthy and diseased hearts using DTMRI. Specifically, changes in myofiber orientation were investigated in a high rate pacing model of dilated cardiomyopathy in swine, and also in excised healthy and diseased human hearts obtained from the Bequest Anatomy program at the University of Minnesota, and LifeSource (the Upper Midwest, a non-profit organ procurement organization). In addition, the mechanical activation due to cardiac pacing from the right ventricular apex was uniquely characterized in a case study of an isolated human heart using MRI, as cardiac pacing from the right ventricular apex is known to chronically result in deleterious changes in fiber orientation and cardiac function. My thesis was divided into several chapters, in the first it was considered paramount to gain a thorough understanding of cardiac MRI. As such, a review of cardiovascular MRI is provided in Chapter 1. The goal of this chapter was to familiarize the reader with cardiac MR and nomenclature, review current techniques to quantify cardiac function with MRI, and to introduce the reader to cardiac diffusion tensor magnetic resonance imaging (DTMRI), which is used in the present work to quantify fiber orientation in the heart. In Chapter 2, a literature review of cardiac fiber orientation and relevant changes resulting from disease is presented, and the measurement of fiber orientation using DTMRI is further discussed. The intent of this chapter is to familiarize the reader with diffusion imaging and the associated parameters used to characterize fiber orientation and tissue integrity. In addition, the methodologies and computational tools developed to measure fiber orientation using a 3 tesla Siemens MRI clinical scanner are described. Chapters 3-5 describe novel investigations in the assessment of fiber orientation using DTMRI. In chapter 3, the effects of decomposition on the diffusion properties of the myocardium were studied in freshly excised human hearts recovered at varying post mortem intervals. From this study, the time frame for the recovery of a human heart was determined to be 3 days, such that the tissue still remains viable for the measurement of fiber orientation using DTMRI. In Chapter 4, a swine model of dilated cardiomyaphy was used to assess in vivo functional and anatomical changes resulting from severe dilation of both the right and left ventricle. Following in vivo functional imaging, ex vivo DTMRI was used to investigate the resultant fiber orientation. Chapter 5 provides a preliminary comparison of fiber orientation in healthy and diseased human hearts, collected within a post-mortem interval of 3 days. Furthermore, in Chapter 6, the mechanical activation during pacing from the right ventricular apex was studied in an isolated human heart. Since pacing from the right ventricular apex is known to cause deleterious changes in fiber orientation, it was of great interest to characterize myocardial strain and motion during RVA pacing as part of my thesis work. In general, this research project has advanced our overall knowledge as to our understanding of ex vivo DTMRI, and the remodeling of the myocardial architecture in heart failure. This described work is not an exhaustive list of the changes in fiber orientation that occur in every type of cardiomyopathy, but provides novel insights into fiber reorganization which occurs in swine due congestive heart failure, and in human hearts excised from patients with a history of heart failure. Additionally, with the development of methodologies and computational tools presented here, and the study of post mortem intervals on the diffusion properties of the myocardium, the framework has been laid for the future analysis of fiber orientation in other cardiomyopathies presented in human cadaveric hearts.
  • Thumbnail Image
    Item
    The Impact of Maladaptive Adipose Tissue on Measures of Heart Failure Severity in Older, Obese Adults With and Without Heart Failure and Preserved Ejection Fraction
    (2022-02) Koepp, Katlyn
    Introduction:Obesity is a leading risk factor for heart failure with preserved ejection fraction (HFpEF), prevalent in more than 70% of patients. Compared to non-obese patients with HFpEF, obese patients with HFpEF demonstrate more profound abnormalities in cardiovascular (CV) structure and function and worse exercise capacity. Visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) are associated with systemic inflammation and impaired nitric oxide availability. These abnormalities are implicated in CV remodeling and functional abnormalities, and may contribute to the development and severity of HFpEF. Despite this evidence, no prior study has directly examined visceral and ectopic adipose tissue depots and their relation to the severity or pathophysiology of HFpEF. Hypothesis:We hypothesized that compared to healthy controls, patients with HFpEF would have more VAT and that greater VAT would be indirectly associated with chronic physical activity (PA), measures of submaximal and peak exercise capacity (VO2), and symptom burden (dyspnea and fatigue). Additionally, we hypothesized that among obese patients with HFpEF, excess EAT would be associated with more severe hemodynamic derangements, increased pericardial restraint, and poorer aerobic capacity. Methods:Body Composition, Submaximal and Peak Exercise Capacity and Chronic Physical Activity Participants with HFpEF (n=78) and healthy control participants (n=50) were prospectively enrolled and underwent cardiopulmonary exercise testing with echocardiography to measure exercise capacity and CV structure and function. To measure the amount (area, cm2) of visceral (VAT), subcutaneous (SAT) and inter/intramuscular (IMAT) adipose tissue, images of the abdomen and thigh were obtained by magnetic resonance imaging (MRI). Chronic PA was measured via accelerometry over a two-week duration. Epicardial Adipose Tissue, Cardiac Structure and Function and Aerobic Capacity Patients referred for invasive cardiopulmonary exercise testing at the Mayo Clinic Cardiac Catheterization Laboratory between 2000 and 2014 were identified retrospectively. Patients with HFpEF and obesity (BMI ≥30 kg/m2) with recent echocardiography (≤1 month of cath) were included in the final analysis (n=169). Invasive exercise hemodynamics and VO2 were obtained during a right heart catheterization with expired gas analysis. Cardiac structure and function and EAT thickness were measured via two-dimensional Doppler and tissue Doppler echocardiography. Conclusions :Our data demonstrate a significantly greater amount of VAT in patients with HFpEF compared to non-HFpEF controls, which was related to greater submaximal symptom severity, poorer peak exercise capacity (peak VO2) and lower levels of chronic PA. Furthermore, our data revealed more abnormal cardiac hemodynamics in obese HFpEF patients with greater EAT than patients with minimal EAT. Future longitudinal studies are needed to examine mechanisms of visceral and other ectopic adipose tissue depots as they relate to the development and severity of HFpEF.
  • Thumbnail Image
    Item
    Instrumented Socks with Novel Sensors for Fluid Accumulation Monitoring
    (2018-08) Zhang, Song
    The overarching goal of this dissertation is to develop wearable sensors that can be integrated onto an instrumented sock for home-based monitoring of lower leg fluid accumulation. Swelling in lower extremities is an early indicator of disease deterioration in cardiac failure, chronic venous insufficiency and lymphedema. At-home wearable monitoring and early detection of fluid accumulation can potentially lead to prompt medical intervention and avoidance of hospitalization. Three types of inexpensive and noninvasive wearable sensors are developed: leg size sensor, tissue elasticity sensor and water content sensor. The innovative leg size sensor developed has unique features of being drift-free, and capable of misalignment-rejection. It has an accuracy of being able to differentiate 1mm changes in diameter, much smaller than any changes that can be detected by the human eye. These features were achieved by using dual magnetic sensors, an inductor for generating alternating magnetic fields, and an unscented Kalman filter estimation algorithm. Elasticity is also an important indicator of fluid accumulation and defines how soft the leg is. The novel elasticity sensor has a simple architecture of two thin-film force transducers and two 3D-printed components, which form a cantilever mechanism. Mathematical models were established for the sensor to estimate tissue elasticity. Lab tests conducted on rubber samples with slightly different softness and human body showed promising results. Several generations of instrumented socks with the leg size sensor and the tissue elasticity sensor were fabricated in the lab. These socks were tested and validated to be accurate and useful in an IRB-approved study on healthy volunteers at Mayo Clinic. The leg size sensor was also integrated into a commercially available pneumatic compression medical device for treating lymphedema. A redesigned and miniaturized leg size sensor was sewed onto a wearable band, which was then attached to the pneumatic pump-based wearable system for monitoring lymphedema treatment progress. Finally, a compact water content sensor was developed. Ultrasound velocity in animal and human tissue has been found to change with water content. A novel integration of magnetic sensing and ultrasonic sensing was utilized to measure ultrasound velocity, and renders the previous bulky device wearable.
  • Thumbnail Image
    Item
    Living with Heart Failure
    (2010-10-29) Riggle, Andrew
    Heart failure is a common condition that affects more than 5 million people in the US. While the condition has no cure, there are several steps you can take including medication, diet, and exercise to control this condition and live longer. Also understanding warning signs and when to contact your physician can help in maintaining your health and preventing dangerous situations.
  • Thumbnail Image
    Item
    The Non-Invasive Application of Electrocardiography in the Optimization of Cardiac Resynchronization Therapy
    (2020-08) Harbin, Michelle
    Cardiac resynchronization therapy (CRT) is intended to reverse electrical dyssynchrony and improve systolic function in heart failure patients. However, roughly 30% of recipients do not clinically or echocardiography benefit, despite advancements with implant techniques and pacing technology, and are considered to be non-responders (Auricchio & Prinzen, 2011). Suboptimal postoperative device programming of the interventricular and atrioventricular delays, and the left ventricular (LV) pacing vector in quadripolar leads, is thought to be a prevailing cause of this persistent non-response (Mullens et al., 2009). Device optimization of pacing configurations is highly underutilized, and research has yet to establish a standardized, patient-specific methodology that can be routinely used in outpatient heart failure clinics (Gras, Gupta, Boulogne, Guzzo, & Abraham, 2009; N. Varma et al., 2019). The use of electrocardiography in device optimization is supported by the notion that synchronous ventricular electrical activation is a requisite for adequate systolic and diastolic function (Nguyen, Verzaal, van Nieuwenhoven, Vernooy, & Prinzen, 2018). Electrocardiography has furthermore shown promise in routine CRT device optimization owning to its non-invasive, inexpensive, and practical attributes. QRS duration shortening during the paced rhythm, as well as metrics of wavefront fusion and cancellation, on 12-lead electrocardiograms have been reported to correlate with subsequent LV reverse remodeling (Gage et al., 2018; Sweeney et al., 2014; Sweeney et al., 2010). Innovations in technology allow for the application of multiple unipolar electrodes placed over the upper anterior and posterior torso (Bank et al., 2018; Johnson et al., 2017; Rickard et al., 2020). The intent of this technology, as depicted in its ability to simultaneously acquire ventricular activation from both anterior and posterior surfaces, is to provide a better assessment of electrical dyssynchrony relative to that of a 12-lead electrocardiogram. Previous reports have shown that this technology can accurately, non-invasively, and efficiently measure electrical heterogeneity in patients with CRT devices (Gage et al., 2017). The purpose of this dissertation is to use this technology to: (1) quantify how a device-based pacing algorithm improves electrical resynchronization, and (2) evaluate the therapeutic window on the corresponding potential of electrical resynchronization during left ventricular unipolar pacing.
  • Thumbnail Image
    Item
    Preclinical Models of Dystrophic Cardiomyopathy and Therapies for the Dystrophic Heart
    (2019-08) Meyers, Tatyana
    Muscular dystrophies are a diverse group of genetic diseases characterized by progressive muscle weakness and deterioration with wide variability in severity and affected muscle groups. Some of the more devastating muscular dystrophies result from the absence of components of the dystrophin-glycoprotein complex (DGC). Disruption of the DGC compromises sarcolemmal integrity in striated muscle, leading to increased myocyte injury and death. These forms of muscular dystrophy often feature both skeletal muscle wasting and marked cardiomyopathy. The most common of these muscular dystrophies is Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene that result in the loss of this large membrane-stabilizing protein. DMD features a childhood onset and leads to premature death at ages ranging from the teens into the 30’s, often from cardiorespiratory failure. DMD is an X-linked disorder, and is usually inherited from carrier mothers who also face a high risk of cardiomyopathy. Sarcoglycanopathies are a rarer group of autosomal recessive Limb Girdle muscular dystrophies (LGMD) that arise from mutations in the sarcoglycan genes, sometimes leading to an aggressive Duchenne-like disease course in patients of both sexes. The heterotetrameric sarcoglycan complex is a key component of the DGC, and its loss induces significant myocyte pathology that can trigger childhood disease onset and premature death. Muscles and hearts devoid of the sarcolgycan complex display hallmark dystrophic pathology, including muscle wasting, loss of ambulation, and a high incidence of lethal dilated cardiomyopathy. The work presented here is driven by efforts to quantify the susceptibility of dystrophic hearts to acute injury caused by increased cardiac workload, and to understand the contribution of angiotensin signaling to dystrophic heart injury. It describes the following key findings: 1) angiotensin receptor blockers (ARBs) can markedly reduce acute injury in dystrophin-null and sarcoglycan-null mouse hearts; 2) female mouse hearts lacking the sarcoglycan complex are significantly protected compared to male hearts, and do not derive the same benefit from ARBs; and 3) mosaic expression of dystrophin in the heart results in elevated vulnerability to injury that is modulated by factors besides dystrophin levels. This work suggests that angiotensin signaling plays an exaggerated role in dystrophic heart injury through mechanisms that may be sex-dependent, and that earlier and more consistent use of angiotensin-blocking therapies has the potential to limit dystrophic cardiomyopathy. Furthermore, it reveals that dystrophic hearts may continue to show significant vulnerability in the context of gene therapies that restore partial dystrophin expression.
  • Thumbnail Image
    Item
    The role of exercise central hemodynamics for the clinical classification of heart failure patients
    (2015-04) Vaniterson, Erik Hoon
    Central hemodynamic evaluation during exercise testing provides critical information for the clinical classification of reduced (HFrEF) or preserved ejection fraction (HFpEF) heart failure (HF) patients. Recent and encouraging observations suggest that non-traditional indices of central hemodynamics can robustly describe cardiac function and pulmonary vascular hemodynamics in healthy individuals and in HF. Therefore, because of emerging evidence in favor of non-traditional indices to describe central hemodynamics in HF, it is unclear what index or indices best describe cardiac function and the heart-lung hemodynamic interaction in HF. Moreover, contributing to the complexity of the pathophysiology underlying the HF syndrome, it is becoming more recognized that neural mechanisms originating within skeletal muscle likely contribute to impaired cardiovascular function and symptoms of these patients. However, it remains unclear what role this neural feedback from skeletal muscle ergoreceptors has in the impaired central hemodynamic response frequently observed during exercise in HF. Therefore, the aims of this dissertation focused on investigating factors to better understand the central hemodynamic response to exercise in HF. In this series of studies we observed that non-traditional measurement of cardiac and pulmonary hemodynamics could describe the central hemodynamic response to exercise in HF. Also, experimental manipulation of neural feedback from skeletal muscle ergoreceptors resulted in observations which suggest pulmonary hemodynamics could be influenced by this mechanism, whereas cardiac function may not be similarly influenced by this pathway in HFrEF. Equally important and relevant to both clinical and research settings, it was observed that non-invasive measurement of stroke volume at peak exercise could be reliably estimated using echocardiography, acetylene rebreathe, and oxygen pulse in HF.
  • Thumbnail Image
    Item
    Septin4 Induces Fibrosis After Cardiac Pressure Overload Injury
    (2023-02) Yucel, Dogacan
    In response to cardiac injury the mammalian heart undergoes ventricular remodeling to maintain cardiac function. These changes are initially considered compensatory, but eventually lead to increased cardiomyocyte apoptosis, reduced cardiac function and fibrosis which are important contributors to the development of HF. The small GTPase Septin4 (Sept4) has previously been implicated in the regulation of regeneration and apoptosis in several organs. A role for Sept4 in regulating the response to cardiac stress is unknown. To investigate the role of Sept4 in cardiac stress response, we performed were subjected to transverse aortic constriction on 10-week-old wild type (WT) and Sept4 knockout (KO) mice. Under homeostatic conditions Sept4 KO mice showed normal cardiac function comparable with WT controls. In response to TAC, WT mice developed reduced cardiac function and HF, accompanied by an increase in cardiomyocyte apoptosis. In contrast, KO mice were protected against injury with maintenance of normal cardiac function and reduced levels of cardiomyocyte apoptosis. Both at baseline and after TAC injury, KO hearts exhibited decreased levels of cardiac ECM deposition and fibrosis compared with WT controls. In support of these data, the level of myofibroblast activation was lower after injury in KO mice. Furthermore, KO mice showed higher levels of cardiac elasticity and improved diastolic function compared with WT controls. Mechanistically, we identified reduced expression of cross- linking collagens at both RNA and protein levels. Molecularly, Sept4 deletion blunted TGF-β signaling and reduced Postn expression. Based on our results, we identified Sept4 as an important regulator of ECM remodeling in the heart. We speculate that the changes in ECM composition observed in KO hearts help alleviate the cardiac pathology resulting from cardiac pressure overload.
  • Thumbnail Image
    Item
  • Thumbnail Image
    Item
    Side Population Cells in the Adult Heart
    (2018-06) Yellamilli, Amritha
    The clinical outcomes for heart failure remain poor because current therapies do not address a critical feature of heart failure – loss of functional cardiomyocytes. To decrease the morbidity and mortality of patients with heart failure, multiple strategies are being developed to replace dead cardiomyocytes with new, functional ones. Adult stem cell transplantation studies have had modest clinical benefits primarily attributed to paracrine effects on several endogenous processes including cardiac regeneration. Many cardiac progenitor cell populations have been isolated from the adult mammalian heart and studied in cell culture or after transplantation; however, their roles in endogenous cardiac regeneration are highly contested. In the thesis work presented here, we used the side population phenotype as an unbiased approach to determine whether an endogenous progenitor cell population exists in the adult mammalian heart. We generated a new Abcg2-driven, lineage-tracing mouse model that efficiently labels side population cells in multiple tissues throughout the body, including the heart. With this mouse model, we first showed that the side population phenotype enriches for endogenous stem cells in the bone marrow and small intestine under homeostatic conditions. In the adult heart, we showed that cardiac side population cells contribute to 21% of newly formed cardiomyocytes either through direct differentiation or fusion. Moreover, cardiac side population cells are responsive to different forms of cardiac injury. Further characterization of cardiac side population cells will help us understand how they can be targeted in vivo for the development of new heart failure therapies.
  • Thumbnail Image
    Item
    Understanding Taiwanese family adaptation to chronic heart failure
    (2014-05) Peng, Szu-Yi
    This hermeneutic phenomenological study explored the lived experiences of individuals and families adapting to living with chronic heart failure, using the Family Adjustment and Adaptation Response Model as the guiding theoretical framework. The report was based on the analyses of 17 interviews with either individuals or families from a medical center in a metropolitan city in Taiwan. The findings showed that chronic heart failure struck the family with ripple effects to multiple areas of family life, including the well-being of individual family members, family functioning and interactions, and the relationships between the family and its social networks and community. The processes of adaptation involved families' efforts to reduce or manage demands by utilizing their existing capabilities, to strengthen and expand resources (including improving family functioning patterns), and to change meanings that shaped how they responded to their situations. Many aspects of the experiences reported by these families in Taiwan were similar to what has been described in previous studies of family experiencing chronic heart failure in other countries. Nevertheless, the findings demonstrated that the influences of cultural or religious beliefs in family meanings played an important role in the process of family juggling the pile-up of demands with their capabilities. Implications for health care providers and future research are offered.