Department of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
Am J Respir Crit Care Med. 2011 May 15;183(10):1411-8. doi: 10.1164/rccm.201003-0354OC. Epub 2010 Dec 3.
Recently it was suggested that patients with pulmonary hypertension (PH) suffer from inspiratory muscle dysfunction. However, the nature of inspiratory muscle weakness in PH remains unclear.
To assess whether alterations in contractile performance and in morphology of the diaphragm underlie inspiratory muscle weakness in PH.
PH was induced in Wistar rats by a single injection of monocrotaline (60 mg/kg). Diaphragm (PH n = 8; controls n = 7) and extensor digitorum longus (PH n = 5; controls n = 7) muscles were excised for determination of in vitro contractile properties and cross-sectional area (CSA) of the muscle fibers. In addition, important determinants of protein synthesis and degradation were determined. Finally, muscle fiber CSA was determined in diaphragm and quadriceps of patients with PH, and the contractile performance of single fibers of the diaphragm.
In rats with PH, twitch and maximal tetanic force generation of diaphragm strips were significantly lower, and the force-frequency relation was shifted to the right (i.e., impaired relative force generation) compared with control subjects. Diaphragm fiber CSA was significantly smaller in rats with PH compared with controls, and was associated with increased expression of E3-ligases MAFbx and MuRF-1. No significant differences in contractility and morphology of extensor digitorum longus muscle fibers were found between rats with PH and controls. In line with the rat data, studies on patients with PH revealed significantly reduced CSA and impaired contractility of diaphragm muscle fibers compared with control subjects, with no changes in quadriceps muscle.
PH induces selective diaphragm muscle fiber weakness and atrophy.
最近有人提出，患有肺动脉高压（PH）的患者存在吸气肌功能障碍。然而，PH 患者吸气肌无力的性质尚不清楚。
评估 PH 患者吸气肌无力是否与收缩性能的改变和膈肌形态有关。
通过单次注射野百合碱（60mg/kg）诱导 Wistar 大鼠 PH。取出膈肌（PH n=8；对照组 n=7）和趾长伸肌（PH n=5；对照组 n=7），以确定体外收缩性能和肌纤维横截面积（CSA）。此外，还测定了蛋白质合成和降解的重要决定因素。最后，测定了 PH 患者膈肌和股四头肌的肌纤维 CSA，并测定了膈肌的单纤维收缩性能。
与对照组相比，PH 大鼠的膈肌条的单次收缩和最大强直收缩力明显降低，力频关系向右侧移位（即相对肌力产生受损）。与对照组相比，PH 大鼠的膈肌纤维 CSA 明显较小，并且与 E3 连接酶 MAFbx 和 MuRF-1 的表达增加有关。PH 大鼠和对照组之间趾长伸肌纤维的收缩性能和形态没有明显差异。与大鼠数据一致，对 PH 患者的研究显示，与对照组相比，膈肌肌纤维 CSA 明显减小，收缩功能受损，而股四头肌无变化。
PH 可引起选择性的膈肌肌纤维无力和萎缩。
