NEUROCHEMICAL EVIDENCE OF CARDIAC SYMPATHETIC ACTIVATION AND INCREASED CENTRAL-NERVOUS-SYSTEM NOREPINEPHRINE TURNOVER IN SEVERE CONGESTIVE-HEART-FAILURE
NEUROCHEMICAL EVIDENCE OF CARDIAC SYMPATHETIC ACTIVATION AND INCREASED CENTRAL-NERVOUS-SYSTEM NOREPINEPHRINE TURNOVER IN SEVERE CONGESTIVE-HEART-FAILURE
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DOI：
10.1016/0735-1097(94)90738-2
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发表时间：
1994-03-01
影响因子：
24
通讯作者：
ESLER, MD
中科院分区：
文献类型：
--
作者：
KAYE, DM;LAMBERT, GW;ESLER, MD
目标。本研究的目的是研究重症心力衰竭患者的心脏交感神经功能，探讨心力衰竭的原因、血流动力学变量和中枢神经系统儿茶酚胺释放对心脏交感神经张力的影响。虽然心力衰竭通常伴有交感神经兴奋，但心力衰竭时心脏交感神经功能的完整性仍然存在争议，特别是与神经放电活动和交感神经重新捕获去甲肾上腺素的能力有关。此外，与心力衰竭引起的交感神经兴奋有关的传入和中枢神经通路的位置尚不清楚。应用放射性示踪技术对41例重度心力衰竭患者和15例健康体检者进行全身生化和心脏交感神经活动的研究。心衰组测定心功能的血流动力学指标，并研究其与交感神经活动的关系。测量颈静脉儿茶酚溢出，研究中枢去甲肾上腺素对交感神经流出的控制。交感神经兴奋在心衰组明显，反映为全身增加了62%(p<；0.001)，心脏去甲肾上腺素外溢率增加了277%(p<；0.001)。伴随这些变化的是去甲肾上腺素前体二羟基苯丙氨酸、交感神经递质神经肽Y和神经元外代谢物3-甲氧基-4-羟基苯甘醇的心脏外溢显著增加。心脏交感神经活动水平与平均肺动脉压显著相关(r=0.59p<；0.001)。二羟基苯丙氨酸和3-甲氧基-4-羟基苯甘醇从脑中溢出的增加，提示中枢去甲肾上腺素能神经元的激活。严重心力衰竭时存在心脏交感神经的激活，与肺动脉压密切相关，与心力衰竭的病因无关。大脑中去甲肾上腺素能神经元的激活也存在，这可能是心力衰竭中观察到的交感兴奋的潜在中枢神经机制。
Objectives. The aim of this study was to characterize cardiac sympathetic nervous function in patients with severe heart failure and to investigate the influence of the cause of heart failure, hemodynamic variables and central nervous system catecholamine release on cardiac sympathetic tone.Background. Although heart failure is generally accompanied by sympathoexcitation, the integrity of cardiac sympathetic nerve function in heart failure remains controversial, particularly in relation to nerve firing activity and to the capacity of sympathetic nerves to recapture norepinephrine. Additionally, the location of the afferent and central neural pathways implicated in heart failure-induced sympathoexcitation remains unclear.Methods. Radiotracer techniques were applied in 41 patients with severe heart failure and 15 healthy control subjects to study the biochemical aspects of whole body and cardiac sympathetic activity. Hemodynamic indexes of cardiac performance were measured in the heart failure group, and their association with sympathetic activity was studied. Jugular venous catechol spillover was measured to study the central noradrenergic control of sympathetic outflow.Results. Sympathoexcitation was evident in the heart failure group, reflected by a 62% increase (p < 0.001) in total body and a 277% increase (p < 0.001) in cardiac norepinephrine spillover rates. These changes were accompanied by significant increases in the cardiac spillover of the norepinephrine precursor dihydroxyphenylalanine, the sympathetic cotransmitter neuropeptide Y and the extraneuronal metabolite 3-methoxy-4-hydroxyphenylglycol. The level of cardiac sympathetic activity was significantly correlated (r = 0.59, p < 0.001) with the mean pulmonary artery pressure. An increase in the spillover of dihydroxyphenylalanine and 3-methoxy-4-hydroxyphenylglycol from the brain was present, suggesting activation of central noradrenergic neurons.Conclusions. Cardiac sympathetic activation is present in severe heart failure, bearing a close relation with pulmonary artery pressures, independent of heart failure etiology. Activation of noradrenergic neurons in the brain is also present and may be the underlying central nervous mechanism of the sympathoexcitation observed in heart failure.