Quantifying the effect of obesity and comorbid hypertension on cardiac function

肥胖是一个主要的公共健康问题，影响着超过三分之一的美国成年人和五分之一的美国人 孩子们。肥胖与心血管死亡风险的增加有关，这可能在一定程度上是由 通过对心脏的直接作用导致功能障碍。然而，肥胖所经历的时间进程 导致心脏功能障碍，肥胖症患者心肌功能障碍的潜在机制 治疗方法还没有完全阐明。我们使用心脏磁共振成像的初步数据 (MRI)显示心肌收缩幅度、收缩同步性和心肌质量异常。 喂食高脂肪西方饮食的小鼠的心脏。这个项目的目标是定义时间进程 这种功能障碍发生在小鼠身上，评估高血压在这一发展中的作用 功能障碍，并将这项工作转化为人类，通过确定我们的儿童肥胖 临床上有心脏功能不全的证据。 该项目有三个具体目标如下：1)确定心肌梗死的时间进程 喂食高脂肪西方饮食的小鼠会出现功能障碍。我们将量化先进的心脏测量方法 在一项纵向研究中评估质量、收缩和松弛以及同步超时的功能 磁共振成像。2)确定降压治疗对高血压发病的影响 喂食高脂肪西方饮食的小鼠的肥大和心功能障碍。吃高脂肪西方饮食的小鼠 发展肥胖相关的高血压，抗高血压治疗是可逆的。然而，这一影响 降压治疗对肥胖小鼠心脏功能的影响尚未进行研究，可能会阐明 其背后的机制。我们将比较吃高脂肪西方饮食的小鼠的心脏功能。 在具体目标1中，给一组小鼠喂食高脂肪的西式饮食和呋喃西林。3)量化心功能 在肥胖儿童中使用先进的核磁共振成像。肯塔基大学最先进的技术 使我们能够将我们在老鼠身上的发现直接转化为我们拥有800多名患者的儿科肥胖诊所。 肥胖对儿童心肌功能的影响在很大程度上是未知的。

Obesity is a major public health problem affecting over one third of adults in the United States and one in five children. Obesity is related to an increased risk of cardiovascular mortality, which may in part be mediated through a direct effect on the heart leading to dysfunction. However, the time course over which obesity leads to cardiac dysfuncfion, the underlying mechanisms of myocardial dysfunction in obesity, and potential treatments have not been fully elucidated. Our preliminary data ufilizing cardiac magnefic resonance imaging (MRI) show abnormalifies in the magnitude of contracfion, synchrony of contraction, and myocardial mass in the hearts of mice fed a high-fat Western diet. The objective of this project is to define the time course over which this dysfunction occurs in mice, evaluate the role of hypertension in the development of this dysfunction, and to translate this work into humans by determining whether children in our pediatric obesity clinic have evidence of cardiac dysfunction. This project has 3 specific aims as follows: 1) Determine the time course over which myocardial dysfunction develops in mice fed a high-fat Western diet. We will quantify advanced measures of cardiac function assessing mass, contraction and relaxation and synchrony overtime in a longitudinal study using magnetic resonance imaging. 2) Determine the effect of anti-hypertensive therapy on the development of hypertrophy and cardiac dysfunction in mice fed a high-fat Western diet. Mice on a high-fat Western diet develop obesity-related hypertension that is reversible with anti-hypertensive therapy. However, the effect of anti-hypertensive therapy on cardiac function in obese mice has not been studied and may elucidate underiying mechanisms. We will compare cardiac function measured in the'mice on a high-fat Western diet in specific aim 1 to a group of mice on a high-fat Western diet and hydralazine. 3) Quantify cardiac function in children with obesity using advanced MRI. State-of-the-art technology at the University of Kentucky enables us to directly translate our findings in mice into our pediatric obesity clinic with over 800 patients. The effect of obesity on myocardial function in children is largely unknown.