Clark A L, Cleland J G
Department of Cardiology, Castle Hill Hospital, Castle Road, Cottingham, Hull, HU16 5JQ.
Heart Fail Rev. 2000 Mar;5(1):101-14. doi: 10.1023/A:1009854325711.
Chronic heart failure is characterised by excess adrenergic activity that augurs a poor prognosis. The reasons for increased adrenergic activity are complex and incompletely understood. The circumstantial evidence relating increased activity to adverse outcome is powerful, but not yet conclusive. In normal subjects, autonomic control of the circulation is predominantly under the control of sympatho-inhibitory inputs from the arterial and cardiopulmonary baroreceptors, with a small input from the excitatory ergo- and chemo-receptors. In heart failure, the situation is reversed, with loss of the restraining input from the baroreceptors and an increase in the excitatory inputs, resulting in excessive adrenergic activity. The circumstantial evidence linking neuroendocrine activation with poor outcome coupled with the clinical success of inhibition of the renin-angiotensin-aldosterone system has long suggested that inhibition of adrenergic activity might be beneficial in heart failure. There is a number of potential ways of achieving this. Improved treatment of heart failure itself may reduce sympathetic drive. There is an interplay between angiotensin II, aldosterone and the sympathetic nervous system, and thus RAAS antagonists, such as angiotensin converting enzyme inhibitors and spironolactone could directly reduce sympathetic activation. Exercise rehabilitation may similarly reduce sympathetic activity.Recently, beta-adrenergic receptor antagonists have been conclusively shown to improve symptoms, reduce hospitalisations and increase survival. However, the demonstration that central reduction of sympathetic activity with agents such as moxonidine increases morbidity and mortality suggests that we do not properly understand the role of sympathetic activation in the pathophysiology of heart failure.
慢性心力衰竭的特征是肾上腺素能活性过高，这预示着预后不良。肾上腺素能活性增加的原因复杂，尚未完全明确。虽然将活性增加与不良结局相关联的间接证据很有力，但尚未得出定论。在正常受试者中，循环系统的自主控制主要受动脉和心肺压力感受器的交感抑制性输入控制，兴奋性运动和化学感受器的输入较少。在心力衰竭时，情况则相反，压力感受器的抑制性输入丧失，兴奋性输入增加，导致肾上腺素能活性过高。长期以来，将神经内分泌激活与不良结局联系起来的间接证据，以及抑制肾素 - 血管紧张素 - 醛固酮系统的临床成功表明，抑制肾上腺素能活性可能对心力衰竭有益。有多种潜在方法可以实现这一点。改善心力衰竭本身的治疗可能会降低交感神经驱动。血管紧张素 II、醛固酮和交感神经系统之间存在相互作用，因此肾素 - 血管紧张素 - 醛固酮系统拮抗剂，如血管紧张素转换酶抑制剂和螺内酯，可以直接降低交感神经激活。运动康复同样可能降低交感神经活性。最近，β - 肾上腺素能受体拮抗剂已被确凿证明可改善症状、减少住院次数并提高生存率。然而，使用莫索尼定等药物中枢性降低交感神经活性会增加发病率和死亡率，这表明我们尚未正确理解交感神经激活在心力衰竭病理生理学中的作用。
