IMPAIRED CHRONOTROPIC RESPONSE TO EXERCISE IN PATIENTS WITH CONGESTIVE HEART-FAILURE - ROLE OF POSTSYNAPTIC BETA-ADRENERGIC DESENSITIZATION
IMPAIRED CHRONOTROPIC RESPONSE TO EXERCISE IN PATIENTS WITH CONGESTIVE HEART-FAILURE - ROLE OF POSTSYNAPTIC BETA-ADRENERGIC DESENSITIZATION
复制标题
DOI：
10.1161/01.cir.80.2.314
复制
发表时间：
1989-08-01
期刊：
影响因子：
37.8
通讯作者：
HARTLEY, LH
中科院分区：
文献类型：
--
作者：
COLUCCI, WS;RIBEIRO, JP;HARTLEY, LH
在46名正常受试者和59名根据峰值运动耗氧量（VO 2）分层的充血性心力衰竭（CHF）患者中研究了导致对运动的心率（HR）响应减弱的机制。在CHF患者中，峰值运动HR和从休息到峰值运动的HR增量降低，并且两者都与峰值VO 2强相关（分别为r = 0.810，p < 0.0001; r = 0.863，p < 0.0001）。CHF患者的运动峰值去甲肾上腺素水平（NE）以及从休息到运动峰值NE的增量并未减弱。静息NE在CHF患者中升高并且与峰值VO 2负相关（r = 0.595，p < 0.0001）。然而，在峰值VO 2与峰值运动NE或NE的运动增量之间没有出现显著的相关性。CHF患者运动时心率和NE（反映窦房结交感神经反应性的间接指标）的比值明显降低，且与运动损伤的严重程度呈负相关。同样，CHF患者对分级异丙肾上腺素输注的HR反应显著降低。匹配或正常受试者和CHF患者不影响上述观察结果。CHF患者输注磷酸二酯酶抑制剂米力农导致运动增加HR和NE的比例显著增加。这些数据强烈地表明，CHF患者中对运动的减弱的HR反应至少部分是由于β-SMA的突触后脱敏。肾上腺素能受体途径
The mechanism responsible for the attenuated heart rate (HR) response to exercise in patients with congestive heart failure (CHF) was investigated in 46 normal subjects and 59 patients with CHF stratified by peak exercise oxygen consumption (.ovrhdot.VO2). The peak exercise HR and the increment in HR from rest to peak exercise were decreased in CHF patients, and both correlated strongly with peak .ovrhdot.VO2 (r = 0.810, p < 0.0001; r = 0.863, p < 0.0001, respectively). Peak exercise norepinephrine level (NE) and the increment in NE from rest to peak exercise were not attenuated in CHF patients. Resting NE was elevated in CHF patients and correlated inversely with peak .ovrhdot.VO2 (r = 0.595, p < 0.0001). However, no significant correlation occurred between peak .ovrhdot.VO2 and either peak exercise NE or the exercise increment in NE. The ratio of the excercise increments in HR and NE, an indirect index of sinoatrial node sympathetic responsiveness, was markedly reduced in CHF patients and was inversely related to the severity of exercise impairment. Likewise, the HR response to a graded isoproterenal infusion was markedly reduced in CHF patients. Age-matching or normal subjects and CHF patients did not affect the foregoing observations. Infusion of CHF patients with the phosphodiesterase inhibitor milrinone caused a significant increase in the ratio of the exercise increments in HR and NE. These data strongly suggest that the attenuated HR response to exercise in CHF patients is due, at least in part, to postsynaptic desensitization of the .beta.-adrenergic receptor pathway.