BETA-ADRENERGIC NEUROEFFECTOR ABNORMALITIES IN THE FAILING HUMAN HEART ARE PRODUCED BY LOCAL RATHER THAN SYSTEMIC MECHANISMS
BETA-ADRENERGIC NEUROEFFECTOR ABNORMALITIES IN THE FAILING HUMAN HEART ARE PRODUCED BY LOCAL RATHER THAN SYSTEMIC MECHANISMS
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DOI：
10.1172/jci115659
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发表时间：
1992-03-01
影响因子：
15.9
通讯作者：
GINSBURG, R
中科院分区：
文献类型：
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作者：
BRISTOW, MR;MINOBE, W;GINSBURG, R
为了研究衰竭心脏中β-肾上腺素能受体神经效应器异常的一般原因，我们测量了来自非衰竭器官捐赠者、因特发性扩张型心肌病（IDC）导致终末期双心室衰竭的受试者、和表现出孤立性右心室衰竭的原发性肺动脉高压（PPH）受试者。相对于未衰竭的PPH左心室，衰竭的PPH右心室表现出（a）β（1）-肾上腺素能受体密度显著降低，（B）组织去甲肾上腺素和神经肽Y显著耗竭，（c）β受体激动剂异丙肾上腺素和锌特罗对腺苷酸环化酶的刺激降低，（d）Gpp（NH）p和毛喉素对腺苷酸环化酶的刺激降低。这些异常在方向上类似于，但通常比失败的IDC右心室的相应结果更明显，而PPH受试者的非衰竭左心室中这些参数的值与器官供体的非衰竭左心室中的值相似。此外，相对于器官捐献者的成对的非衰竭PPH左心室和非衰竭右心室，PPH受试者的衰竭右心室表现出MnCl 2对腺苷酸环化酶的刺激减少。这些数据表明：（a）在衰竭的人类心脏中存在的肾上腺素能神经效应器异常是由于局部机制;全身过程不会产生β-肾上腺素能神经效应器异常。(b)PPH患者的压力超负荷衰竭右心室表现出腺苷酸环化酶催化亚单位活性降低，这是一种以前在衰竭人类心脏中没有描述过的异常。
In order to investigate the general cause of beta-adrenergic receptor neuroeffector abnormalities in the failing human heart, we measured ventricular myocardial adrenergic receptors, adrenergic neurotransmitters, and beta-adrenergic receptor-effector responses in nonfailing and failing hearts taken from nonfailing organ donors, subjects with endstage biventricular failure due to idiopathic dilated cardiomyopathy (IDC), and subjects with primary pulmonary hypertension (PPH) who exhibited isolated right ventricular failure. Relative to nonfailing PPH left ventricles, failing PPH right ventricles exhibited (a) markedly decreased beta(1)-adrenergic receptor density, (b) marked depletion of tissue norepinephrine and neuropeptide Y, (c) decreased adenylate cyclase stimulation in response to the beta agonists isoproterenol and zinterol, and (d) decreased adenylate cyclase stimulation in response to Gpp(NH)p and forskolin. These abnormalities were directionally similar to, but generally more pronounced than, corresponding findings in failing IDC right ventricles, whereas values for these parameters in nonfailing left ventricles of PPH subjects were similar to values in the nonfailing left ventricles of organ donors. Additionally, relative to paired nonfailing PPH left ventricles and nonfailing right ventricles from organ donors, failing right ventricles from PPH subjects exhibited decreased adenylate cyclase stimulation by MnCl2.These data indicate that: (a) Adrenergic neuroeffector abnormalities present in the failing human heart are due to local mechanisms; systemic processes do not produce beta-adrenergic neuroeffector abnormalities. (b) Pressure-overloaded failing right ventricles of PPH subjects exhibit decreased activity of the catalytic subunit of adenylate cyclase, an abnormality not previously described in the failing human heart.