Cardiac Sympathetic Nerve Activity: understanding normal control and the causes of the increase in heart failure

心脏交感神经活动：了解正常控制和心力衰竭增加的原因

• 批准号: nhmrc : 232313
• 负责人: Prof Clive May
• 金额: $ 35.42万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/cardiac-sympathetic-nerve-heart-failure/77305
• 关键词: Cardiac; Sympathetic; Nerve; Activity; understanding

Heart failure is a condition in which the heart muscle becomes weak and is unable to pump sufficient blood around the body to provide adequate perfusion of the organs. This results in breathlessness, lethargy, fatigue, mental confusion and eventually death. At present the life expectancy of patients with heart failure is poor, with a 5 year survival of 25% in men and 38% in women. It is the only form of heart disease that is increasing, the reason being that thousands of patients who have survived heart attacks or had coronary bypass operations go on to develop heart failure. In heart failure there is a very large increase in the activity of the nerves that stimulate cardiac rate and contractility, the cardiac sympathetic nerves. This increase in activity is detrimental, higher levels of activity predict greater morbidity and a reduced life span. The mechanisms causing the increase in cardiac sympathetic nerve activity are unknown, but greater understanding is essential if new and improved treatments are to be developed for patients with heart failure. Only two groups in the world measure cardiac nerve activity in conscious animals, neither is studying heart failure. We therefore have a unique opportunity to investigate the factors that control the activity of the cardiac nerves in the healthy state and to establish the causes of the increase in activity in heart failure. In particular, we will investigate how reflex control mechanisms, circulating hormones that are increased in heart failure and specific mechanisms in the brain act to control cardiac nerve activity in the normal state and what changes in these mechanisms lead to the preferential increase in cardiac nerve activity in heart failure. These findings will provide a detailed understanding of the mechanisms controlling cardiac nerve activity in the normal healthy state and increased knowledge of the factors that lead to the preferential activation of the cardiac nerves in heart failure.

心力衰竭是指心脏肌肉变得虚弱，无法将足够的血液输送到身体各处，为器官提供足够的灌流。这会导致呼吸困难、昏昏欲睡、疲劳、精神混乱，最终导致死亡。目前，心力衰竭患者的预期寿命很低，男性和女性的5年存活率分别为25%和38%。它是唯一一种正在增加的心脏病，原因是数以千计的心脏病患者在心脏病发作后幸存下来或接受了冠状动脉旁路手术后继续发展为心力衰竭。在心力衰竭时，刺激心率和收缩能力的神经--心脏交感神经--的活性有很大的增加。这种活动的增加是有害的，活动水平越高，发病率就越高，寿命就越短。导致心脏交感神经活性增加的机制尚不清楚，但如果要为心力衰竭患者开发新的和改进的治疗方法，更多的了解是必不可少的。世界上只有两个小组测量清醒动物的心脏神经活动，研究心力衰竭的小组也没有。因此，我们有一个独特的机会来研究在健康状态下控制心脏神经活动的因素，并确定心力衰竭时活动增加的原因。特别是，我们将研究反射控制机制、心力衰竭时增加的循环激素和大脑中的特定机制是如何控制正常状态下的心脏神经活动的，以及这些机制中的哪些变化导致心力衰竭时心脏神经活动的优先增加。这些发现将提供对正常健康状态下控制心脏神经活动的机制的详细了解，并增加对导致心力衰竭时心脏神经优先激活的因素的了解。