Cardiovascular Disease (CVD) accounts for the leading number of deaths worldwide. Prior to menopause, women exhibit lower rates of CVD compared to age-matched men, however, risks for women increase with menopause. Studies show estrogen loss and age exacerbating cardiac β-adrenergic receptor (β-AR) signaling and contractile function. We therefore hypothesized that prolonged estrogen deficiency and chronic β-adrenergic stimulation cause decreases in cardiac function and increases in fibrosis in aged female hearts. Female mice underwent either an ovariectomy (OVX) or a control SHAM surgery at 10 weeks old and were infused with Isoproterenol for three days via mini osmotic pumps in order to induce chronic β-adrenergic stimulation 12-months post-surgery. Our results show prolonged estrogen deficiency from the OVX exacerbates cardiac function and fibrosis compared to SHAM. These differences highlight the importance of continued research on cardiac estrogen deficiency mechanisms to understand the long-term effects in the heart during both CVD and menopause.

The number one killer of women in the United States is cardiovascular disease (CVD). Cardiovascular risk factors (CVRFs) include advancing age, cigarette smoking, diabetes, dyslipidemia, family history, hypertension, obesity, sedentary lifestyle and high intake of saturated fats and low dietary fiber. A women’s risk for development of CVD dramatically increases after menopause and with the number of CVRFs. CVD is often preventable. Evidence supports addressing CVRFs reduction early (in the pre-menopausal years) through heart-healthy behaviors such as increasing physical activity, promoting healthy eating, moderate alcohol consumption and not smoking. Therefore, understanding premenopausal women’s CVRFs knowledge is an important area of inquiry. In addition, the Nemcek Wellness Model suggests that self-nurturance, as well as knowledge, may be an important factor for explaining women’s wellness behaviors. Thus, the purpose of this study was to investigate knowledge of CVRFs, level of self-nurturance and the performance of heart-healthy behaviors in women ages 35 to 55 years. This study used a cross sectional survey design and venue sampling. The survey included demographic questions, the Self Nurturance Survey, the Heart Disease Facts Questionnaire, the Physical Activity Questionnaire, Prime Screen, and questions about financial strain, cigarette smoking, and alcohol use. The sample included 136 women (survey response rate = 57%), the majority of whom were white (94.9%), married (80.1%), did not smoke (80.1%) and rarely drank alcohol (57.4%). Results indicated that study participants were very knowledgeable about CVRFs. (Mean knowledge score = 19.53, possible range = 0 to 25 with higher scores indicating greater knowledge). Knowledge did not predict physical activity (p = .07), diet (p = .08) or smoking status (p = .11) in this sample. Self-nurturance was moderately correlated (r = .33) with consuming a heart-healthy diet. Hypotheses derived from the Nemcek Wellness Model were not supported in this study. More research is needed to identify factors that will help women translate knowledge into heart-healthy behaviors.

The initial use of optical fibres to transmit laser energy intravascularly was accompanied by a high rate of perforations and the production of inadequate vascular channels when used for recanalisation. The laser thermal probe - in which all laser energy is converted into heat by a metal cap at the tip of the fibre, prior to tissue application - was one of the earliest modifications designed to overcome these problems. The studies in this thesis were concerned with the application of the laser thermal probe to percutaneous peripheral and coronary artery angioplasty and His bundle ablation. In vitro studies were commenced in March 1987 when the first (argon) laser generator was installed in the cardiac catheterisation laboratory at Guy's Hospital and these were followed by clinical studies in three groups of patients: nine with peripheral artery occlusions, three with coronary artery stenoses and four with supraventricular arrhythmias using either argon or Nd-YAG energies. Suggestions that enhanced safety might be possible with on-line monitoring and/or control of the probe temperature were studied by recording the temperature responses in simulated circulations at flow rates observed clinically. The highly variable temperatures recorded in blood indicate that these measures are unlikely to contribute to improvements in either efficacy or clinical safety. An earlier report of successful peripheral artery recanalisation using the laser thermal probe was confirmed in the patients studied here, though a learning curve was evident. Coronary laser angioplasty had also been performed in a few patients with a similar device but without as much success. A more flexible "over the wire" laser probe was assessed here, first in cadaver coronary arteries and then in three patients undergoing coronary angioplasty. The lack of success seen with this laser thermal probe relates to the considerable differences found between peripheral and coronary arteries: percutaneous accessibility, vessel size and the susceptibility to thermal injury being the most important. These aspects and subsequent developments in coronary laser angioplasty are discussed further. The final chapter considers a hitherto new area for laser thermal probe application the interruption of arrhythmia circuits. Cadaver and electrophysiological studies indicated that ablation of the bundle of His might be possible with this device - without the need for a general anaesthetic. The course of the first patient ever to undergo this procedure is described, as well as the implications for percutaneous His bundle ablation using other energy sources.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21677号 / 医博第4483号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 木村 剛, 教授 湊谷 謙司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Atrial fibrillation (AFIB) is the most common heart rhythm abnormality and is associated with significant morbidity and mortality. While the treatment of AFIB involves strategies of rate with or without rhythm control, it is also essential to strategize appropriate therapies to prevent thromboembolic complications arising from AFIB. Previously, anticoagulation was the main treatment option which exposed patients to higher than usual risk of bleeding. However, with the advent of new technology, novel therapeutic options aimed at surgical or percutaneous exclusion or occlusion of the left atrial appendage in preventing thromboembolic complications from AFIB have evolved. This review evaluates recent advances and therapeutic options in treating AFIB with a special focus on both surgical and percutaneous interventions which can reduce and/or eliminate thromboembolic complications of AFIB.

Excerpt: Dr Meier and colleagues1 present intriguing data that individuals with a first acute myocardial infarction (AMI) were less likely than matched controls to have used tetracycline antibiotics or quinolones in the previous 3 years. The authors raise the possibility that organisms susceptible to these antibiotics may be involved in the pathogenesis of coronary heart disease. However, several methodological limitations lead to other possible explanations for the observed associations.

Atherosclerosis is a chronic inflammatory disorder of medium and large vessels. Immune signaling and dyslipidemia are two of several processes which influence lesion development in atherosclerosis. Cannabinoids, such as those found in marijuana, exert their effects through two cannabinoid receptors, CB1 and CB2. Recent studies using CB2 knockout mice and CB2-selective ligands have shed light on a protective role of CB2 in early stages of atherosclerosis. However, the role of CB2 in advanced stages of atherosclerosis remains unclear. To determine if CB2 plays a role in advanced atherosclerotic lesion composition and progression, we investigated the effects of systemic CB2 gene deletion on advanced atherogenesis in Ldlr-null mice fed an atherogenic high fat diet (HFD) for 20-24 weeks. CB2 deficiency did not significantly affect aortic root lesion area, however, CB2-/- mice had a significant increase (~1.9 fold) in the percentage of abdominal aorta surface occupied by lesion. CB2-/- mice also displayed increased lesional macrophage content (~2.3 fold) and an unstable phenotype characterized by significantly reduced smooth muscle cell/macrophage ratio and increased matrix metalloproteinase-9 activity and mineralization. These results suggest that although CB2 does not affect the size of atherosclerotic lesions, it does modulate the cellular and extracellular matrix composition and promotes a stable phenotype. CB2+/+ and CB2-/- mice were also subjected to treatments with either CB2-selective agonist, JWH-015, or antagonist, SR144528, over the last four weeks of a 24 week atherogenic diet to identify the effects of CB2 stimulation on calcification of advanced lesions. No change was observed in body weight or cholesterol in response to either treatment. SR144528 reduced triglycerides and mineralization of aortic root lesions in CB2+/+ mice only. Aortic Runx2 and osteopontin were increased in response to JWH-015 by a CB2-dependent mechanism. Administration of synthetic cannabinoids in an ex vivo organ culture of CB2+/+ aortas revealed increased vascular calcification in response to CB2 blockade and decreased vascular calcification in response to CB2 activation. All together, these results support a protective role for CB2 in late stages of atherosclerosis and suggests that drugs targeting CB2 may be beneficial in the treatment of advanced atherosclerosis by affecting osteogenic mechanisms implicated in the mineralization of lesions.

With the rising rates of heart disease incidents in the United States and the increase in lung cancer deaths as well, many individuals suffer and get their treatments compromised due to these diseases. Especially considering that many lung cancer and heart disease patients are over 70 years of age, treatment options and success rates drop significantly. Due to this, a great concern is raised for patients with co-existing heart disease and lung cancer. This was a case-control study that assessed lung cancer treatment options and success rates for patients with co-existing heart disease. We used research papers that discussed lung cancer treatment success in patients with heart disease to gather data on the subject. Furthermore, we used the 2020 NHIS to gather demographic data on the interviewed adults who answered the questions regarding lung cancer and heart disease. At the start, we hypothesized that there wasn’t going to be a high success rate for lung cancer treatment in patients with heart disease due to the invasive nature of the treatment available. We found that most patients with pre-existing heart disease that sought lung cancer treatment had their condition worsened due to severe invasive treatments such as chemotherapy and radiotherapy. In most surgical lung cancer treatment options, patients with pre-existing heart disease were more likely to die after the operation than patients without pre-existing heart disease. Currently and in future times, it’s more likely to find individuals with both diseases due to the rising culture which endorses poor habits in eating, alcohol consumption, smoking, and the utilization of drugs. Understanding the difficulty and dangers that are found in current treatment options for heart disease patients suffering from lung cancer will allow for innovation and improvement in treating such patients.

Heart disease is the leading cause of death in the United States. While many factors can contribute to heart disease, stress plays a significant role. To better understand the mechanisms underlying the impact of stress on cardiovascular function, the intent of this thesis is to focus on the adenylate cyclase (AC) family of isoforms as key mediators of stress hormone signaling. AC operates downstream of ß-adrenergic receptor signaling to produce cAMP as a second messenger. There are at least 9 AC isoforms, all of which have different regulatory properties, but it is not clear which of these isoforms are expressed in the developing heart. Thus, there is still much to be discovered. This project seeks to establish a baseline understanding of AC isoform-specific expression patterns in the developing heart to better comprehend the role of these isoforms in development, beginning in the embryonic period and extending into the postnatal and adult ages. To accomplish this, we extracted RNA from flash-frozen hearts at embryonic days 10.5 and 15.5 (e10.5 and e15.5) as well as postnatal days 9 (juvenile), 38 (pre-pubescent) and young adult (2-3 months). Subsequently, quantitative polymerase chain reaction (qPCR) was performed with isoform-specific primers. To verify the amplification, PCR products were run on ethidium bromide gels. Our initial results show that many isoforms are undetected at e10.5, but AC1-3 and AC6-9 were expressed from e15.5 onward. Only AC4 was robustly expressed at all ages, and AC2 and 8 were strongly upregulated during the embryonic period. Our results suggest that AC isoforms 2, 4, and 8 have an important developmental function from early in the embryonic period. Future studies will seek to test the AC isoforms at later postnatal and adult ages and localize AC expression in various areas of the heart.

No description available.