Plasma neprilysin concentration during recovery from acute illness.
Plasma neprilysin concentration during recovery from acute illness.
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急性疾病恢复期间的血浆中性溶酶浓度。
DOI：
10.1093/eurheartj/ehy456
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发表时间：
2018
影响因子：
39.3
通讯作者：
N. Vodovar
中科院分区：
文献类型：
--
作者：
M. Arrigo;H. Nougué;J. Launay;A. Mebazaa;N. Vodovar
我们的研究小组最近描述了在心力衰竭（HF）患者中移除衰竭心室并植入全人工心脏导致可溶性脑啡肽酶（sNEP）浓度和活性显著降低，随后均部分恢复。1这些数据，结合在心脏收缩功能受损患者中观察到的正跨心梯度和中性跨肺梯度，表明心脏是HF中sNEP的关键来源。Takahama et al. 2在他们的信中讨论了急性HF恢复期间血浆sNEP浓度是否改变的问题。使用与我们使用的不同的检测方法，他们观察到sNEP浓度低于我们以前在急性HF 3患者中测量的浓度，并且发现入院和出院之间没有显著差异。基于这些结果，他们提出sNEP可能是主要血流动力学改变的指标，而不是HF严重程度。为了验证Takahama等人的观察结果，我们测量了50名先前描述的因急性呼吸困难入院的患者（28名急性HF和22名急性非心源性呼吸困难）在入院时和出院前（平均住院时间13天）的sNEP浓度。[3]与Takahama等人相反，我们观察到sNEP浓度在入院和出院之间增加，无论急性HF患者呼吸困难或左心室射血分数的病因如何（图1）。此外，我们没有观察到入院和出院时sNEP浓度之间的任何相关性（斯皮尔曼sq=-0.04，P= 0.76）。因此，我们的数据表明，sNEP浓度在急性条件下降低，并在临床改善后至少部分恢复。在急性条件下sNEP浓度降低的潜在机制仍有待建立，但血液动力学改变（宏观和/或微循环）是潜在的候选者。根据这些结果，在植入全人工心脏的两名患者中，sNEP活性的最初显著降低可能是由于sNEP的心室源的去除以及剧烈的血液动力学改变。第2周后sNEP浓度的部分恢复可能表明生物体适应了新的血液动力学条件。在切除心室后或临床改善后，其他器官参与sNEP部分恢复的程度尚未确定。多种原因可以解释Takahama等人报告的数据与
Our group recently described that the removal of failing ventricles and the implantation of a total artificial heart in heart failure (HF) patients led to a marked decrease in soluble neprilysin (sNEP) concentration and activity, both partially recovering afterward. 1 These data, in conjunction with a positive trans-cardiac gradient and a neutral trans-pulmonary gradient observed in patients with impaired cardiac systolic function, indicate the heart as a critical source of sNEP in HF. In their letter, Takahama et al. 2 addressed the question whether plasma sNEP concentrations are altered during recovery from acute HF. Using a different assay compared to the one we use, they observed lower sNEP concentrations compared to what we previously measured in patients admitted for acute HF 3 and found no significant differences between admission and discharge. Based on those results, they proposed that sNEP could be an indicator of major haemodynamic alterations rather than HF severity. To verify the observations of Takahama et al., we measured sNEP concentration at admission and before discharge (median length of hospital stay 13 days) in 50 previously described patients admitted for acute dyspnoea (28 acute HF and 22 acute non-cardiac dyspnoea). 3 In contrast to Takahama et al., we observed an increase in sNEP concentrations between admission and discharge, regardless of the aetiology of dyspnoea or the left ventricular ejection fraction in acute HF patients (Figure 1). Furthermore, we did not observe any correlation between sNEP concentrations at admission and discharge (Spearman’sq=-0.04, P= 0.76). Our data, therefore, suggest that sNEP concentration is decreased in acute conditions and recovers at least partially after clinical improvement. The mechanisms underlying the decrease in sNEP concentration in acute conditions remains to be established, but haemodynamic alterations (macro-and/or microcirculation) are potential candidates. In light of these results, the initial marked decrease in sNEP activity in the two patients implanted with a total artificial heart likely resulted from the removal of the ventricular source of sNEP combined with drastic haemodynamic alterations. The partial recovery in sNEP concentrations occurring after week 2 likely indicates the adaptation of the organism to new haemodynamic conditions. To which extent other organs are involved in the partial recovery of sNEP after removal of the ventricles or after clinical improvement is yet to be determined. Multiple reasons may explain the difference between the data reported by Takahama et al. and