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Chronic heart failure is one of the commonest fatal diseases in the world. Much work has been done to reveal its complicated pathogenesis and develop effective therapy. Xinmailong (XML), a compound extracted from Periplaneta americana, has been launched on the market in Mainland China as a proprietary medication for treating patients with chronic heart failure. Although it is highly effective, its mechanism of action is still not completely understood. In this study, the results of calcium (〖Ca〗^(2+)) imaging demonstrated that XML increased electrical impulse-induced intracellular calcium ([〖Ca〗^(2+)]i), in H9c2 cells, an rat embryonic cardiomyocytes cell line. This effect was dependent on extracellular 〖Ca〗^(2+) but not the 〖Ca〗^(2+) store from sarcoplasmic reticulum because XML had no effect on thapsigargin -induced 〖Ca〗^(2+) release. The effect of XML was inhibited by ML218-HCl but not nimodipine, indicating that XML interacted with T-type 〖Ca〗^(2+) channels but not L-type 〖Ca〗^(2+) channels. Unlike KB-R7943, which is a sodium calcium exchanger inhibitor, XML did not affect [〖Ca〗^(2+)]i in the absence of electric stimulation, implying that XML did not work on sodium calcium exchanger. Ouabain, a sodium-potassium ATPase inhibitor, increased the electrical impulse-induced [〖Ca〗^(2+)]i and the effect of ouabain and XML were not additive, suggesting that the site of action of ouabain and XML was overlapped. Biochemical assay on phosphate concentration showed that XML was able to inhibit the activity of sodium-potassium ATPase. Our study also demonstrated that XML reduced the production of reactive oxygen species in H9c2 cells. Western blotting showed that such antioxidant properties mechanism might involve the increased expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and heme oxygenase 1. In conclusion, our study has provided evidence that XML increases [〖Ca〗^(2+)]i level by activating T-type 〖Ca〗^(2+) channels and inhibiting sodium-potassium ATPase. The antioxidant effect of XML may also contribute to the cardioprotective effect of XML but further investigation is required. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Philosophy

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Echocardiography has an prominent role in the era of CRT by virtue of its non-invasive nature with high feasibility and reproducibility. The clinical applications include not only quantification of the change in systolic function, hemodynamics, LV volume, or mitral regurgitation, but also assessment of systolic dyssynchrony. A number of new echocardiographic techniques were employed in this study, such as tissue Doppler imaging (TDI) and its post-processing modalities including strain, strain rate and displacement mappings, tissue synchronization imaging (TSI), as well as three-dimentional (3D) echocardiography. / For heart failure patients with wide QRS complexes who received CRT, LV volumes, cardiac function and synchronicity were shown to change acutely between CRT-on and CRT-off modes by both 2D and 3D echocardiography methods. Furthermore, the usefulness of 3D echocardiography and its accuracy in assessing volumetric changes / Systolic dyssynchrony, which illustrates discoordinated contraction of the heart, is relatively common in heart failure patients, in particular those with prolonged QRS complexes. It is caused by electromechanical delay in some regions of the failing heart and will result in further reduction of cardiac function. Cardiac resynchronization therapy (CRT) is a rapidly evolving pacing modality for advanced heart failure, characterized by implantation of the left ventricular (LV) lead through coronary sinus to the free wall region. It is recommended to patients who have refractory heart failure despite optimal medical treatment, LV dilatation with ejection fraction lower than 35%, and prolonged QRS duration on surface ECG. / The main findings were as followed: The Ts-SD was 17.0+/-7.8ms in normal control, 33.8+/-16.9ms in narrow QRS group and 42.0+/-16.5ms in wide QRS group, respectively. The prevalence of systolic dyssynchrony in heart failure population was 43% in the narrow QRS group, and 64% in the wide QRS group, when a Ts-SD of > 32.6 ms (+2 SD of normal controls) was used to define significant dyssynchrony. QRS duration does not have a linear relationship with systolic dyssynchrony. / TSI was useful to predict a reverse remodeling and gain in ejection fraction after CRT. Qualitative identification of the latest peak systolic contraction at the lateral wall was a quick and specific guide to predict a favorable reverse remodeling response while quantitative computation of "Asynchrony Index" from 12 LV segments in ejection phase was beneficial in the absence of lateral wall delay. In conclusion, the improvement of cardiac function and LV reverse remodeling after CRT is more obvious in heart failure patients with wide QRS complex and echocardiographic evidence of significant systolic dyssynchrony. Reverse remodeling is not only an objective measure of favorable responses, but also a prognosticator of disease outcomes. "Asynchrony Index" is a strong predictor of LV reverse remodeling response after CRT. Assessment of systolic dyssynchrony by various echocardiographic tools is promising, however, further studies are needed to compare the predictive values of different parameters objectively and prospectively. / We performed echocardiography with TDI in 200 subjects, including 67 patients with heart failure and narrow QRS complexes (≤ 120ms), 45 patients with heart failure and wide QRS complexes (>120ms), and 88 normal controls, which served as a polit study. Severity and prevalence of systolic dyssynchrony were assessed by the maximal difference in time to peak myocardial systolic velocity (Ts-dif-12) and the standard deviation (Ts-SD) of the 12 LV segments. / We recruited a group of seventy patients with chronic heart failure who fulfilled the established criteria and received CRT. Serial echocardiographic assessment with clinical evaluation was performed at baseline, predischarge, 1-month, 3-month, 6-month and long-term follow up. The objective was to demonstrate the improvement of cardiac function and dyssynchrony after CRT by echocardiographic parameters, in particular the reduction of LV end-systolic volume (LVESV) which is also known as reverse remodeling, and its relationship with the improvement in clinical status and prognosis. We also attempted to identify dyssynchrony parameters which are useful in predicting LV reverse remodeling after CRT. / Zhang Qing. / "October 2006." / Adviser: Yu Cheuk-Man. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5852. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Background and aims: Heart failure (HF) is a life threatening condition and optimal handling is necessary to reduce risk of therapy failure. The aims of this thesis were: (Paper I) to examine whether BNP (B-type natriuretic peptide)-guided HF treatment improves morbidity and mortality when compared with HF therapy implemented by a treating physician at sites experienced in managing patients with HF according to guidelines; (Paper II) to investigate how to define a responder regarding optimal cut-off level of BNP to predict death, need for hospitalisation, and worsening HF and to determine the optimal time to apply the chosen cut-off value; (Paper III) to evaluate how Health-Related Quality of Life (HR-QoL) is influenced by natriuretic peptide guiding and to study how HR-QoL is affected in responders compared to non-responders; (Paper IV) to evaluate the impact of patient age on clinical outcomes, and to evaluate the impact of duration of the HF disease on outcomes and the impact of age and HF duration on BNP concentration. Methods: A randomized, parallel group, multi-centre study was undertaken on 279 patients with HF and who had experienced an episode of worsening HF with increased BNP concentration. The control group (n=132) was treated according to HF guidelines and in the BNP-guided group (n=147) the HF treatment algorithm goal was to reduce BNP concentration to < 150 ng/L in patients < 75 years and <300 ng/L in patients > 75 years (Paper I), and to define the optimal percentage decrease in BNP and at what point during the follow-up to apply the definition (Paper II). To compare the BNP-guided group with the conventional HF treated group (Paper I), and responders and non-responders (Paper II) regarding HR-QoL measured with Short Form 36 (SF-36) at study start and at study end (Paper III) and to evaluate if age or HF duration influenced the HF outcomes and the influence of BNP on age and HF duration (Paper IV). Results: The primary outcome (mortality, hospitalisation and worsening HF) was not improved by BNP-guided HF treatment compared to conventional HF treatment or in any of the secondary outcome variables (Paper I). Applying a BNP decrease of at least 40 percent in week 16 (compared to study start) and/or a BNP<300 ng/L demonstrated the best risk reduction for cardiovascular mortality, by 78 percent and 89 percent respectively for HF mortality (Paper II). The HR-QoL improved in four domains in the BNP-guided group and in the control group in six of eight domains; however there were no significant differences between the groups (Paper III). For responders the within group analysis showed improvement in four domains compared to the non-responders that improved in one domain; however there were no significant differences between the two groups. There were improvements in HR-QoL in all four groups (Paper III). Age did not influence outcome but HF duration did. HF duration was divided into three groups: HF duration less than 1 year (group 1), 1-5 years (group 2) and >5 years (group 3). A 1.65-fold increased risk could be demonstrated in those with HF duration of more than five years compared to patients with short HF duration. The BNP concentration was increased with increased age, and there was a better response regarding BNP decrease in NP-guiding in patients with short HF duration, independent of age (Paper IV). Conclusions: There were no significant differences between BNP-guided HF treatment group and the group with conventional HF treatment as regards mortality, hospitalisation or HR-QoL. The responders to HF treatment showed a significantly better outcome in mortality and hospitalisation compared to non-responders but no significant differences in HR-QoL. The duration of HF might be an important factor to consider in HF treatment by BNP-guiding in the future.

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Chronic heart failure (HF) is a condition that affects more than 900,000 people in the UK. Mortality rates associated with the condition are high, with nearly 20% of patients dying within one year of diagnosis. Continuous monitoring and risk stratification can help identify patients at risk of deterioration and may consequently improve patients' likelihood of survival. Current repeated-measure risk stratification techniques for HF patients often rely on subjective perception of symptoms, such as breathlessness, and markers of fluid retention in the body (e.g. weight). Despite the common use of such markers, studies have shown that they offer limited effectiveness in predicting HF-related events. This thesis set out to identify and evaluate new markers for repeated-measure risk stratification of HF patients. It started with an exploration of traditional HF measurements, including weight, blood pressure, heart rate and symptom scores, and aimed to improve the performance of these measurements using a data-driven approach. A multi-variate model was developed from data acquired during a randomised controlled trial of remotely-monitored HF patients. The rare occurrence of HF-related adverse events during the trial required the developement of a careful methodology. This methodology helped identify the markers with most predictive ability, which achieved moderate performance at identifying patients at risk of HF-related adverse events, clearly outperforming commonly-used thresholds. Subsequently, this thesis explored the potential value of additional, accelerometer-derived physical activity (PA) and sleep markers. For this purpose, the ability of accelerometer-derived markers to differentiate between individuals with and without HF was evaluated. It was found that markers that summarise the frequency and duration of different PA intensities performed best at differentiating between the two groups and may therefore be most suitable for future use in repeated-measure applications. As part of the analysis of accelerometer-derived HF markers, a gap in the methodology of automated accelerometer processing was identified, namely the need for self-reported sleep-onset and wake-up information. As a result, Chapter 5 of this thesis describes the development and evaluation of a data-driven solution for this problem. In summary, this thesis explored both traditional and new, accelerometer-derived markers for the early detection of HF deterioration. It utilised sound methodology to overcome limitations faced by sparse and unbalanced datasets and filled a methodological gap in the processing of signals from wrist-worn accelerometers.

M.Cur. / The intra-aortic balloon pump is a volume displacement device that is used to provide partial support to the left ventricle. The IABP is an effective and general used circulatory support device. The nursing of a patient on IABP therapy requires demonstration of specific clinical competence by the critical care nurse. Clinical competence is defined as the ability of the critical care nurse to integrate his/her knowledge, skills and values and to demonstrate it during nursing of a patient on IABP with the aim to promote the patient's health. The aim of this research had been to evaluate the clinical competence of the critical care nurse during the nursing of a patient on IABP, and to make recommendations according to that regarding education, the practice and research. The relationship between the components of clinical competence namely knowledge, skills and values that were set as aim, were also established. A quantitative, contextual, descriptive, correlational research design had been used in the study to compile a self-developed evaluation instrument that had been used to evaluate the clinical competence of the critical care nurse. The evaluation instrument consisted of a questionnaire that evaluated the knowledge of the critical care nurse, a check list that evaluated the skills of the critical care nurse and a semantic differential scale that evaluated the values of the critical care nurse during the nursing of a patient on IABP therapy. After the data was analyzed, it appeared that critical care nurses don't possess the necessary knowledge and skills to nurse patients on IABP, and as such are not clinically competent to nurse patients on IABP. iii Recommendations were made regarding education, the practice and research in order to improve the clinical competence of critical care nurses during the nursing of a patient on IABP therapy

Han, Jinghao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 182-204). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese.

Cardiac Resynchronization Therapy (CRT) is a treatment option for heart failure patients with ventricular dyssynchrony. CRT corrects for dyssynchrony by electrically stimulating the septal and lateral walls of the left ventricle (LV), forcing synchronous con- traction and improving cardiac output. Current selection criteria for CRT rely upon the QRS duration, measured from a surface electrocardiogram, as a marker of electrical dyssynchrony. Unfortunately, 30-40% of patients undergoing CRT fail to benefit from the treatment. A multitude of studies have shown that presence of mechanical dyssynchrony in the LV is an important factor in determining if a patient will benefit from CRT. Furthermore, recent evidence suggests that patient response can be improved by placing the LV pacing lead in the most dyssynchronous or latest contracting segment. The overall goal of this project was to develop methods that allow for accurate assessment and display of regional mechanical dyssynchrony throughout the LV and at the site of the LV pacing lead. To accomplish this goal, we developed a method for quantifying regional dyssynchrony from standard short-axis cine magnetic resonance (MR) images. To assess the effects of LV lead placement, we developed a registration method that allows us to project the LV lead location from dual-plane fluoroscopy onto MR measurements of cardiac function. By applying these techniques in patients undergoing CRT, we were able to investigate the relationship between regional dyssynchrony, LV pacing lead location, and CRT response.