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

心力衰竭是一种心肌变得虚弱并且不能将足够的血液泵送到身体周围以提供器官的充分灌注的状况。这会导致呼吸困难、嗜睡、疲劳、精神混乱，最终死亡。目前，心力衰竭患者的预期寿命很短，男性5年生存率为25%，女性为38%。它是唯一一种正在增加的心脏病，原因是成千上万的心脏病发作或冠状动脉搭桥手术后幸存的患者继续发展为心力衰竭。在心力衰竭中，刺激心率和收缩力的神经（心脏交感神经）的活动大幅增加。这种活动的增加是有害的，更高水平的活动预示着更高的发病率和缩短的寿命。引起心脏交感神经活动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，就必须有更多的了解。世界上只有两个研究小组测量了清醒动物的心脏神经活动，也没有研究心力衰竭。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，并确定心力衰竭活动增加的原因。特别是，我们将研究如何反射控制机制，循环激素增加心力衰竭和大脑中的特定机制，以控制心脏神经活动在正常状态下，这些机制的变化导致心脏神经活动的优先增加心力衰竭。这些发现将提供一个详细的了解机制控制心脏神经活动在正常的健康状态和增加的知识的因素，导致心脏神经的优先激活心力衰竭。

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.