Esler M, Kaye D
Baker Medical Research Institute, Alfred Lane, Prahran, 3181, Melbourne, Australia.
Heart Fail Rev. 2000 Mar;5(1):17-25. doi: 10.1023/A:1009889922985.
Recent demonstration that the level of sympathetic nervous drive to the failing heart in patients with severe heart failure is a major determinant of prognosis, and that mortality in heart failure is reduced by beta-adrenergic blockade, indicate the clinical relevance of heart failure neuroscience research. The cardiac sympathetic nerves are preferentially stimulated in severe heart failure, with the application of isotope dilution methods for measuring cardiac norepinephrine release to plasma indicating that in untreated patients cardiac norepinephrine spillover is increased as much as 50-fold, similar to levels of release seen in the healthy heart during near maximal exercise. This preferential activation of the cardiac sympathetic outflow contributes to arrhythmia development and to progressive deterioration of the myocardium, and has been linked to mortality in both mild and severe cardiac failure. Although the central nervous system mechanisms involved in the sympathetic nervous activation at present remain uncertain, increased intracardiac diastolic pressure seems to be one peripheral reflex stimulus, and increased forebrain norepinephrine turnover an important central mechanism.Additional neurophysiological abnormalities present in the failing human heart include release of the sympathetic cotransmitters, epinephrine and neuropeptide Y, at high levels more typical of their release during exercise in healthy subjects, and the possible presynaptic augmentation of norepinephrine release from the cardiac sympathetic nerves by the regionally released epinephrine. Following on the demonstrable benefit of beta-adrenergic blockade in heart failure, additional antiadrenergic measures (central suppression of sympathetic outflow with imidazoline binding agents such as clonidine, blocking of norepinephrine synthesis by dopamine-beta-hydroxylase inhibition, antagonism of neuropeptide Y) are now under active investigation.
最近的研究表明，严重心力衰竭患者衰竭心脏的交感神经驱动水平是预后的主要决定因素，并且β-肾上腺素能阻滞剂可降低心力衰竭的死亡率，这表明心力衰竭神经科学研究具有临床相关性。在严重心力衰竭中，心脏交感神经会被优先刺激，应用同位素稀释法测量心脏去甲肾上腺素释放到血浆中的量表明，未经治疗的患者心脏去甲肾上腺素溢出增加多达50倍，类似于健康心脏在接近最大运动时的释放水平。心脏交感神经流出的这种优先激活会导致心律失常的发生和心肌的进行性恶化，并且与轻度和重度心力衰竭的死亡率都有关联。尽管目前参与交感神经激活的中枢神经系统机制尚不确定，但心室内舒张压升高似乎是一种外周反射刺激，而前脑去甲肾上腺素周转率增加是一种重要的中枢机制。衰竭的人类心脏中还存在其他神经生理异常，包括交感神经共递质肾上腺素和神经肽Y的高水平释放，这在健康受试者运动时更为典型，以及局部释放的肾上腺素可能对心脏交感神经去甲肾上腺素释放产生突触前增强作用。继β-肾上腺素能阻滞剂在心力衰竭中显示出明显益处之后，目前正在积极研究其他抗肾上腺素能措施（用可乐定等咪唑啉结合剂对交感神经流出进行中枢抑制、通过抑制多巴胺-β-羟化酶来阻断去甲肾上腺素合成、拮抗神经肽Y）。
