先天性心脏病中的吸气肌功能障碍和限制性肺功能损害：与免疫炎症反应及运动不耐受的关联。

Inspiratory muscle dysfunction and restrictive lung function impairment in congenital heart disease: Association with immune inflammatory response and exercise intolerance.

作者信息

Spiesshoefer Jens, Orwat Stefan, Henke Carolin, Kabitz Hans-Joachim, Katsianos Stratis, Borrelli Chiara, Baumgartner Helmut, Nofer Jerzy-Roch, Spieker Maximilian, Bengel Philipp, Giannoni Alberto, Dreher Michael, Boentert Matthias, Diller Gerhard Paul

机构信息

Respiratory Physiology Laboratory, Department of Neurology with Institute for Translational Neurology, University of Muenster, Muenster, Germany; Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.

Department of Cardiology III, University Hospital Muenster, Muenster, Germany.

出版信息

Int J Cardiol. 2020 Nov 1;318:45-51. doi: 10.1016/j.ijcard.2020.06.055. Epub 2020 Jul 4.

DOI:10.1016/j.ijcard.2020.06.055

PMID:32634497

Abstract

BACKGROUND

In adult patients with congenital heart disease (ACHD), both underlying disease and lung restriction contribute to exercise intolerance. In ACHD the yet incompletely understood mechanism underlying restricted ventilation may be inspiratory muscle weakness. Therefore, this study comprehensively evaluated inspiratory muscle function in ACHD and associations with systemic inflammation and the clinical severity of exercise intolerance.

METHODS

30 ACHD patients (21 men, 35 ± 12 years) and 30 healthy controls matched for age, gender and body mass index underwent spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound. Six-minute walking distance (6MWD) and New York Heart Association functional class were used to quantify exercise intolerance. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assays.

RESULTS

ACHD patients showed lower forced vital capacity (FVC), and maximum inspiratory (PImax) and expiratory (PEmax) pressures compared with controls (all p < 0.05). On ultrasound, ACHD patients showed a lower diaphragm thickening ratio (2.3 ± 0.5 vs. 2.8 ± 0.9, p < 0.01) and lower diaphragm excursion velocity during a voluntary sniff maneuver (5.7 ± 2.2 vs. 7.6 ± 2.0 cm/s, p < 0.01). Respiratory parameters, such as FVC (r = 0.53; p < 0.01) and PImax (r = 0.43; p = 0.02), correlated with 6MWD. Furthermore, amino terminal pro B-type natriuretic peptide levels were inversely correlated with FVC (r = -0.54; p < 0.01). Circulating pro-inflammatory cytokines were markedly increased, and IL-6 was correlated with 6MWD, dyspnea, and biomarkers of heart, lung and inspiratory muscle function (all p < 0.05).

CONCLUSIONS

Our findings show that diaphragm dysfunction is present in ACHD and relates to restrictive ventilation disorder and exercise intolerance, possibly mediated by increased IL-6 levels.

摘要

背景

在成年先天性心脏病（ACHD）患者中，基础疾病和肺功能受限均会导致运动耐量下降。在ACHD患者中，通气受限的潜在机制尚未完全明确，可能是吸气肌无力。因此，本研究全面评估了ACHD患者的吸气肌功能及其与全身炎症和运动耐量临床严重程度的相关性。

方法

30例ACHD患者（21例男性，年龄35±12岁）和30名年龄、性别及体重指数相匹配的健康对照者接受了肺活量测定、口腔闭塞压测量及膈肌超声检查。采用6分钟步行距离（6MWD）和纽约心脏协会心功能分级来量化运动耐量。使用酶联免疫吸附测定法测量白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）水平。

结果

与对照组相比，ACHD患者的用力肺活量（FVC）、最大吸气压力（PImax）和最大呼气压力（PEmax）较低（均p<0.05）。超声检查显示，ACHD患者的膈肌增厚率较低（2.3±0.5对2.8±0.9，p<0.01），在自主吸气动作期间膈肌移动速度较低（5.7±2.2对7.6±2.0cm/s，p<0.01）。呼吸参数，如FVC（r=0.53；p<0.01）和PImax（r=0.43；p=0.02）与6MWD相关。此外，氨基末端前B型利钠肽水平与FVC呈负相关（r=-0.54；p<0.01）。循环促炎细胞因子明显升高，IL-6与6MWD、呼吸困难以及心脏、肺和吸气肌功能的生物标志物相关（均p<0.05）。