Floras John S
Mount Sinai Hospital and University Health Network Division of Cardiology, and the University of Toronto, Toronto, Ontario, Canada.
J Am Coll Cardiol. 2009 Jul 28;54(5):375-85. doi: 10.1016/j.jacc.2009.03.061.
Disturbances in cardiovascular neural regulation, influencing both disease course and survival, progress as heart failure worsens. Heart failure due to left ventricular systolic dysfunction has long been considered a state of generalized sympathetic activation, itself a reflex response to alterations in cardiac and peripheral hemodynamics that is initially appropriate, but ultimately pathological. Because arterial baroreceptor reflex vagal control of heart rate is impaired early in heart failure, a parallel reduction in its reflex buffering of sympathetic outflow has been assumed. However, it is now recognized that: 1) the time course and magnitude of sympathetic activation are target organ-specific, not generalized, and independent of ventricular systolic function; and 2) human heart failure is characterized by rapidly responsive arterial baroreflex regulation of muscle sympathetic nerve activity (MSNA), attenuated cardiopulmonary reflex modulation of MSNA, a cardiac sympathoexcitatory reflex related to increased cardiopulmonary filling pressure, and by individual variation in nonbaroreflex-mediated sympathoexcitatory mechanisms, including coexisting sleep apnea, myocardial ischemia, obesity, and reflexes from exercising muscle. Thus, sympathetic activation in the setting of impaired systolic function reflects the net balance and interaction between appropriate reflex compensatory responses to impaired systolic function and excitatory stimuli that elicit adrenergic responses in excess of homeostatic requirements. Recent observations have been incorporated into an updated model of cardiovascular neural regulation in chronic heart failure due to ventricular systolic dysfunction, with implications for the clinical evaluation of patients, application of current treatment, and development of new therapies.
心血管神经调节紊乱会随着心力衰竭的恶化而进展，影响疾病进程和生存。长期以来，左心室收缩功能障碍所致的心力衰竭一直被认为是一种全身性交感神经激活状态，其本身是对心脏和外周血流动力学改变的一种反射反应，这种反应最初是适当的，但最终会变成病理性的。由于心力衰竭早期动脉压力感受器反射对心率的迷走神经控制受损，因此人们认为其对交感神经流出的反射缓冲也会相应降低。然而，现在人们认识到：1）交感神经激活的时间进程和程度是特定于靶器官的，并非全身性的，且与心室收缩功能无关；2）人类心力衰竭的特征包括对肌肉交感神经活动（MSNA）的动脉压力反射调节快速反应、对MSNA的心肺反射调节减弱、与心肺充盈压升高相关的心脏交感兴奋反射，以及非压力反射介导的交感兴奋机制的个体差异，包括并存的睡眠呼吸暂停、心肌缺血、肥胖以及运动肌肉的反射。因此，收缩功能受损情况下的交感神经激活反映了对收缩功能受损的适当反射性代偿反应与引发肾上腺素能反应超过稳态需求的兴奋性刺激之间的净平衡和相互作用。最近的观察结果已被纳入心室收缩功能障碍所致慢性心力衰竭的心血管神经调节更新模型中，这对患者的临床评估、当前治疗方法的应用以及新疗法的开发具有重要意义。
